Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metformin to Type 2 Diabetes Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02202161
Recruitment Status : Completed
First Posted : July 28, 2014
Results First Posted : November 6, 2017
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: GSK2330672
Drug: Placebo
Drug: Sitagliptin
Drug: Metformin
Enrollment 70
Recruitment Details The study was conducted from 27 August 2014 to 30 January 2015. After interim analysis of safety, tolerability, pharmacodynamic and/or pharmacokinetic (PK) data, GSK2330672 10 and 20 milligram (mg) doses were dropped and GSK2330672 60 mg was added.
Pre-assignment Details A total of 187 participants were screened, of these, 112 were screen failures and 75 entered the run-in period. Five participants were withdrawn prior to taking a metformin dose in the 14 days of run-in period. A total of 64 participants were randomized to receive investigational product, as 6 participants were withdrawn prior to randomization.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID Run-in Only
Hide Arm/Group Description Participants were randomized to receive matching placebo solution of GSK2330672 orally twice daily (BID) for 14 days. Participants drank the contents of dosing bottle (45 milliliters [mL]) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing. Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Period Title: Overall Study
Started 13 5 5 9 9 10 13 6
Completed 12 4 5 9 8 9 13 0
Not Completed 1 1 0 0 1 1 0 6
Reason Not Completed
Adverse Event             1             1             0             0             0             1             0             0
Did not meet continuation criteria             0             0             0             0             0             0             0             3
Physician Decision             0             0             0             0             0             0             0             3
Withdrawal by Subject             0             0             0             0             1             0             0             0
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID Run-in Only Total
Hide Arm/Group Description Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing. Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing. Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing. Total of all reporting groups
Overall Number of Baseline Participants 13 5 5 9 9 10 13 6 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants 6 participants 70 participants
52.1  (6.97) 54.0  (4.30) 56.2  (8.50) 57.1  (5.86) 55.0  (4.27) 54.8  (7.47) 53.7  (6.79) 55.5  (3.51) 54.5  (6.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants 6 participants 70 participants
Female
4
  30.8%
3
  60.0%
4
  80.0%
2
  22.2%
6
  66.7%
4
  40.0%
5
  38.5%
3
  50.0%
31
  44.3%
Male
9
  69.2%
2
  40.0%
1
  20.0%
7
  77.8%
3
  33.3%
6
  60.0%
8
  61.5%
3
  50.0%
39
  55.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants 6 participants 70 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
1
   1.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
2
  22.2%
0
   0.0%
0
   0.0%
0
   0.0%
3
   4.3%
Black or African American
3
  23.1%
1
  20.0%
0
   0.0%
1
  11.1%
3
  33.3%
0
   0.0%
3
  23.1%
1
  16.7%
12
  17.1%
White
10
  76.9%
4
  80.0%
4
  80.0%
8
  88.9%
4
  44.4%
9
  90.0%
10
  76.9%
5
  83.3%
54
  77.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour])
Hide Description The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value. It was assessed on Baseline, Day 7 and 14. Data for fasting and weighted mean (WM) AUC(0-24 hour) glucose is provided. Statistics for least square mean is provided and participants withdrawing early were excluded. Results were based on an analysis of covariance (ANCOVA) model: change from Baseline = Baseline + treatment.
Time Frame Baseline (Day -1) and Day 14 (Fasting Pre-dose [within 15 minutes of dose], 30 minutes, 1, 1.5, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, 14 [bed time] and 24 hours) and Day 7 (30 minutes, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, and 24 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was used which was defined as all participants enrolled into the study who received at least one dose of study drug (including GSK2330672, GSK2330672-matched placebo, sitagliptin and metformin). Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Mg/deciliter
Fasting, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 9 participants 13 participants
-6.58  (16.357) -8.25  (6.500) -1.40  (23.050) -38.56  (24.744) -34.38  (19.398) -24.78  (13.414) -24.54  (33.955)
Fasting, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 9 participants 13 participants
-10.00  (19.207) -22.75  (11.354) -16.20  (28.709) -48.67  (32.650) -36.13  (23.117) -40.22  (19.156) -38.38  (16.439)
WM AUC(0-24 hour), Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 9 participants 13 participants
3.91  (20.668) -12.14  (11.828) -7.01  (17.262) -25.33  (25.819) -21.47  (18.419) -14.84  (18.569) -26.63  (23.610)
WM AUC(0-24 hour), Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 9 participants 13 participants
-9.94  (18.458) -22.44  (15.928) -17.80  (16.990) -37.48  (32.909) -32.22  (22.948) -45.54  (21.010) -35.85  (20.233)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-25.61 to 23.27
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.22
Confidence Interval (2-Sided) 95%
-9.84 to 36.27
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -21.77
Confidence Interval (2-Sided) 95%
-41.43 to -2.10
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -23.10
Confidence Interval (2-Sided) 95%
-42.63 to -3.57
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -11.79
Confidence Interval (2-Sided) 95%
-30.85 to 7.28
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -10.04
Confidence Interval (2-Sided) 95%
-27.66 to 7.57
Estimation Comments Comparison for fasting, Day 7
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.14
Confidence Interval (2-Sided) 95%
-37.72 to 7.43
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.10
Confidence Interval (2-Sided) 95%
-23.66 to 19.45
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -20.66
Confidence Interval (2-Sided) 95%
-38.75 to -2.57
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -21.70
Confidence Interval (2-Sided) 95%
-39.70 to -3.71
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -10.62
Confidence Interval (2-Sided) 95%
-28.62 to 7.38
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -26.03
Confidence Interval (2-Sided) 95%
-41.94 to -10.12
Estimation Comments Comparison for WM AUC(0-24 hour), Day 7
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12.10
Confidence Interval (2-Sided) 95%
-33.56 to 9.36
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.33
Confidence Interval (2-Sided) 95%
-15.91 to 24.57
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -25.29
Confidence Interval (2-Sided) 95%
-42.56 to -8.02
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -19.97
Confidence Interval (2-Sided) 95%
-37.12 to -2.82
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -21.82
Confidence Interval (2-Sided) 95%
-38.56 to -5.08
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -18.01
Confidence Interval (2-Sided) 95%
-33.48 to -2.55
Estimation Comments Comparison for fasting, Day 14
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -11.20
Confidence Interval (2-Sided) 95%
-33.21 to 10.81
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.80
Confidence Interval (2-Sided) 95%
-16.22 to 25.81
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.23
Confidence Interval (2-Sided) 95%
-32.86 to 2.41
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -17.01
Confidence Interval (2-Sided) 95%
-34.56 to 0.53
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -23.94
Confidence Interval (2-Sided) 95%
-41.49 to -6.39
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg BID
Comments An estimation approach was used.
Type of Statistical Test Superiority or Other
Comments An analysis of covariance (ANCOVA) model with a fixed effect term for treatment was fitted with the post-Baseline pharmacodynamic parameter value minus Baseline (Day -1 parameter value) as the dependent variable and Baseline as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -19.45
Confidence Interval (2-Sided) 95%
-34.96 to -3.93
Estimation Comments Comparison for WM AUC(0-24 hour), Day 14
2.Primary Outcome
Title Number of Participants With Incidence and Nature of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition and alanine aminotransferase (ALT) >= 3× upper limit of normal (ULN) and total bilirubin >=2 × ULN (>35% direct) or ALT >=3 × ULN and international normalized ratio >1.5.
Time Frame Up to 14 days (treatment period)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
9
  69.2%
4
  80.0%
5
 100.0%
5
  55.6%
8
  88.9%
8
  80.0%
8
  61.5%
Any SAE
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants With Abnormal Hematology With Potential Clinical Concern (PCI)
Hide Description Hematology parameters included platelet, red blood cell (RBC) count, mean corpuscular volume (MCV), neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Data for parameters with above and below the PCI is provided.
Time Frame Up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Abnormal Clinical Chemistry With PCI
Hide Description Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, fasting glucose, total carbon dioxide, gamma glutamyltransferase (GGT), albumin, sodium, calcium, alkaline phosphatase (ALP), total protein, total carbon dioxide and triglycerides. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Data for parameters with above and below the PCI is provided. The normal range (NR) and PCI definition for abnormal parameters are: ALT (NR: 0-44, 0-32, 2-33; PCI: >=2×upper limit of normal [ULN]); AST (NR: 0-40; PCI: >=2× ULN) and total bilirubin (NR: 0.00-20.52; PCI: >=1.5× ULN).
Time Frame Up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, high
1
   7.7%
0
   0.0%
2
  40.0%
2
  22.2%
2
  22.2%
1
  10.0%
1
   7.7%
AST, high
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Total Bilirubin, hgh
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants With Abnormal Urinalysis Data
Hide Description Urinalysis included urine occult blood: trace to 3+, glucose: negative to 3+, protein: negative to 2+ and ketones: trace to negative by dipstick and microscopic examination included cast, cellular cast, granular cast, hyaline cast (none seen to 1) and RBC: 0-2, 3-10, 11-30, >30, WBC: none seen, 0-5, 1, 2, 4, <5, 6-10, 11-30, 19, >30). The plus sign increases with a higher level of occult blood, glucose, ketones, proteins, RBC, WBC in the urine: 1+: slightly positive, 2+: positive, 3+: high positive. Participants were categorized as none seen or 1 based on the absence or presence, respectively, of cast, cellular cast, granular cast and hyaline cast. Higher value indicates higher abnormality.
Time Frame Baseline (pre-dose Day -1), Day 7 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
Urine Occult Blood, Day -1, Trace
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Occult Blood, Day -1, small
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Occult Blood, Day-1, 3+
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Occult Blood, Day 7, Trace
0
   0.0%
1
  20.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Occult Blood, Day 7, Trace intact
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Occult Blood, Day 7, small
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Occult Blood, Day 7, 1+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Occult Blood, Day 15, Trace
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Occult Blood, Day 15, small
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Occult Blood, Day 15, 2+
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-Casts, Day 7, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-Cellular Casts, Day -1, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
   7.7%
Urine Microscopy-Cellular Casts, Day 7, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
1
   7.7%
Urine Microscopy-Cellular Casts, Day 15, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
1
   7.7%
Urine Microscopy-Granular Casts, Day -1, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
   7.7%
Urine Microscopy-Granular Casts, Day 7, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
1
   7.7%
Urine Microscopy-Granular Casts, Day 15, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
1
   7.7%
Urine Glucose, Day -1, Trace
1
   7.7%
0
   0.0%
1
  20.0%
1
  11.1%
1
  11.1%
2
  20.0%
0
   0.0%
Urine Glucose, Day -1, 1+
0
   0.0%
0
   0.0%
0
   0.0%
3
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Glucose, Day -1, 2+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Glucose, Day -1, 3+
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
2
  15.4%
Urine Glucose, Day 7, Trace
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
1
  11.1%
1
  10.0%
1
   7.7%
Urine Glucose, Day 7, 1+
1
   7.7%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-Hyaline Casts, Day -1, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
   7.7%
Urine Microscopy-Hyaline Casts, Day 7, None seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
   7.7%
Urine Microscopy-Hyaline Casts, Day 7, 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Microscopy-Hyaline Casts, Day 15, none seen
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
1
   7.7%
Urine Ketones, Day 7, Trace
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Protein, Day -1, 1+
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Protein, Day 7, 2+
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Protein, Day 15, Trace
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Urine Protein, Day 15, 1+
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-RBC, Day -1, none seen
2
  15.4%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-RBC, Day -1, 0-2
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-RBC, Day -1, 3-10
0
   0.0%
1
  20.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-RBC, Day -1, 11-30
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-RBC, Day 7, none seen
1
   7.7%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  15.4%
Urine Microscopy-RBC, Day 7, 0-2
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Urine Microscopy-RBC, Day 15, none seen
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-RBC, Day 7, 3-10
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day -1, none seen
2
  15.4%
2
  40.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day -1, 0-5
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day -1, 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day -1, 4
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day -1, 6-10
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day -1, 11-30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day -1, >30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 7, 0-5
1
   7.7%
1
  20.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day 7, 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day 7, <5
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 7, 11-30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
1
   7.7%
Urine Microscopy-WBC, Day 7, 19
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 7, >30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 15, 0-5
1
   7.7%
0
   0.0%
1
  20.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day 15, 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 15, 2
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day 15, 4
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Urine Microscopy-WBC, Day 15, 11-30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine Microscopy-WBC, Day 15, >30
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
6.Primary Outcome
Title Summary of Urinalysis Data-mean Specific Gravity
Hide Description Data for mean specific gravity is provided. Specific gravity is a measure of the amount of material dissolved in the urine. Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance. Normal urine has a specific gravity between 1.010 and 1.020.
Time Frame Baseline (pre-dose Day -1), Day 7 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Ratio
Day -1 Number Analyzed 13 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1.0193  (0.00694) 1.0182  (0.00581) 1.0128  (0.00421) 1.0190  (0.00618) 1.0172  (0.00610) 1.0189  (0.00780) 1.0148  (0.00706)
Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1.0196  (0.00753) 1.0208  (0.00904) 1.0184  (0.00896) 1.0191  (0.00739) 1.0194  (0.00726) 1.0208  (0.00859) 1.0160  (0.00790)
Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
1.0188  (0.00403) 1.0193  (0.00435) 1.0158  (0.00259) 1.0132  (0.00471) 1.0121  (0.00348) 1.0160  (0.00787) 1.0140  (0.00815)
7.Primary Outcome
Title Summary of Urinalysis Data-mean pH
Hide Description Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Time Frame Baseline (pre-dose Day -1), Day 7 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Unit on a scale
Day -1 Number Analyzed 13 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
5.73  (0.388) 6.00  (0.000) 6.10  (0.224) 6.11  (0.220) 5.83  (0.354) 5.95  (0.438) 5.85  (0.516)
Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
5.83  (0.389) 5.90  (0.224) 6.00  (0.000) 5.89  (0.220) 5.61  (0.486) 5.95  (0.284) 5.69  (0.435)
Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
5.88  (0.377) 5.88  (0.250) 6.00  (0.000) 6.00  (0.000) 5.72  (0.565) 6.06  (0.167) 5.88  (0.416)
8.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings Any Time Post-Baseline
Hide Description Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Participants with normal, abnormal not clinically significant and abnormal clinically significant ECG is presented.
Time Frame Up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
Normal
9
  69.2%
4
  80.0%
4
  80.0%
8
  88.9%
6
  66.7%
6
  60.0%
9
  69.2%
Abnormal not clinically significant
4
  30.8%
0
   0.0%
1
  20.0%
1
  11.1%
3
  33.3%
4
  40.0%
4
  30.8%
Abnormal clinically significant
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title Change From Baseline in Vital Signs Assessments-temperature
Hide Description The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.
Time Frame Baseline (pre-dose Day -1) and, Day 7, 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Degree Celsius
Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
-0.133  (0.2570) -0.280  (0.4764) 0.040  (0.4393) 0.033  (0.3937) 0.033  (0.2062) 0.010  (0.4458) 0.015  (0.4451)
Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
-0.208  (0.3370) 0.025  (0.1708) -0.040  (0.2966) -0.111  (0.5622) 0.056  (0.2744) -0.178  (0.5995) 0.062  (0.3404)
10.Primary Outcome
Title Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.
Time Frame Baseline (pre-dose Day -1) and Day 7, 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
DBP, Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
-0.083  (6.8152) -1.600  (8.5323) -6.600  (1.9494) -1.556  (10.7948) -4.111  (4.9861) -2.700  (6.7007) -2.462  (7.6770)
DBP, Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
0.750  (6.1070) -2.750  (4.5735) 1.800  (5.8481) -1.333  (9.1104) -1.667  (3.9370) -2.667  (6.3048) -0.769  (5.0852)
SBP, Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
2.250  (8.4544) -4.000  (10.2225) -15.600  (6.1482) 2.222  (17.6973) 1.222  (9.1211) -4.300  (10.9245) -5.462  (10.3571)
SBP, Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
2.167  (8.5049) -4.500  (10.4722) 0.600  (11.8870) -5.111  (11.9105) -1.000  (9.3541) -2.111  (9.5321) -4.385  (9.2334)
11.Primary Outcome
Title Change From Baseline in Vital Signs Assessments-heart Rate
Hide Description The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.
Time Frame Baseline (pre-dose Day -1) and Day 7, 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 7 Number Analyzed 12 participants 5 participants 5 participants 9 participants 9 participants 10 participants 13 participants
-0.500  (8.1296) 9.200  (8.2280) 4.400  (7.4027) 0.556  (5.2941) 4.667  (4.0620) 1.400  (7.0269) -0.769  (6.2471)
Day 15 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 9 participants 13 participants
0.083  (3.1176) 0.250  (6.3443) 9.200  (3.1937) -0.444  (8.2932) 4.889  (7.4237) 0.000  (8.8034) 1.846  (9.1364)
12.Primary Outcome
Title Number of Bowel Movements (Stool Frequency) as Rated Using the Bristol Stool Form Scale (BSFS) Across Days 1 to 14
Hide Description The site staff classified participant's stools and record the date and time of occurrence after any bowel movement that occurs while participants were in residence in the clinic. BSFS is scale between type 1-7, it measured the shape of the stool, type 1: separate hard lumps, like nuts; type 2: sausage shaped but lumpy; type 3: like a sausage or snake but with cracks on its surface; type 4: like a sausage or snake, smooth and soft; type 5: soft blobs with clear cut edges; type 6: fluffy pieces with ragged edges, a mushy stool and type 7: watery, no solid pieces. Participants were discharged after they have had at least one bowel movement after the Day 14 dosing and after the investigator/designee had reviewed the Day 15 end of study questions.
Time Frame Up to Day 15 (administered after every in-house bowel movement)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID Run-in Only
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13 0
Mean (Standard Deviation)
Unit of Measure: Count of bowel movements
15.2  (9.29) 28.2  (17.47) 38.4  (10.74) 35.0  (18.49) 37.3  (30.72) 35.9  (21.67) 15.0  (10.96)
13.Primary Outcome
Title Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14
Hide Description The site staff classified participant's stools and record the date and time of occurrence after any bowel movement that occurs while participants were in residence in the clinic. BSFS is scale between type 1-7, it measured the shape of the stool, type 1: separate hard lumps, like nuts; type 2: sausage shaped but lumpy; type 3: like a sausage or snake but with cracks on its surface; type 4: like a sausage or snake, smooth and soft; type 5: soft blobs with clear cut edges; type 6: fluffy pieces with ragged edges, a mushy stool and type 7: watery, no solid pieces. Participants were discharged after they have had at least one bowel movement after the Day 14 dosing and after the investigator/designee had reviewed the Day 15 end of study questions.
Time Frame Up to Day 15 (administered after every in-house bowel movement)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed. For each BSFS scale rating the "Number of Participants Analyzed" represents the number of participants reporting that rating not the number evaluated.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Number
Unit of Measure: Events
BSFS scale rating, 1 event : Events Number Analyzed 2 participants 0 participants 0 participants 1 participants 0 participants 1 participants 2 participants
2 1 1 2
BSFS scale rating, 2 events : Events Number Analyzed 2 participants 0 participants 2 participants 1 participants 0 participants 0 participants 7 participants
6 2 1 10
BSFS scale rating, 3 events : Events Number Analyzed 5 participants 0 participants 2 participants 1 participants 3 participants 5 participants 10 participants
28 4 1 6 5 36
BSFS scale rating, 4 events : Events Number Analyzed 11 participants 2 participants 5 participants 6 participants 6 participants 8 participants 9 participants
56 7 18 19 21 24 41
BSFS scale rating, 5 events : Events Number Analyzed 8 participants 2 participants 4 participants 7 participants 3 participants 9 participants 9 participants
30 2 8 26 9 30 26
BSFS scale rating, 6 events : Events Number Analyzed 9 participants 5 participants 5 participants 9 participants 8 participants 10 participants 9 participants
59 81 113 181 250 201 70
BSFS scale rating, 7 events : Events Number Analyzed 7 participants 4 participants 5 participants 8 participants 7 participants 8 participants 3 participants
16 51 47 86 50 98 10
14.Primary Outcome
Title Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels)
Hide Description GSRS is a rating scale consisting of 15 items. Each item was scored from 1: no discomfort at all, 2: minor discomfort, 3: mild discomfort, 4: moderate discomfort, 5: moderately severe discomfort, 6: severe discomfort, 7: very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 1 to 7; a score of 1 indicates that no symptoms are present, and a score of 7 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity. There were 5 defined syndrome scores and 1 overall score that was derived by computing the mean of the scores for specific subsets of questions as indicated below: abdominal pain (1, 4, 5); reflux syndrome (2, 3); diarrhea syndrome (11, 12, 14); indigestion syndrome (6, 7, 8, 9); constipation syndrome (10, 13, 15) and overall GSRS (1-15). The data is presented for participants with worsening of symptoms in >=2 levels.
Time Frame Day 7 and 14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13
Measure Type: Count of Participants
Unit of Measure: Participants
Pain/discomfort in upper abdomen, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
2
  22.2%
0
   0.0%
0
   0.0%
0
   0.0%
Heartburn, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Acid reflux, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Hunger pains, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
1
  11.1%
1
  10.0%
0
   0.0%
Nausea, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Rumbling, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
2
  40.0%
0
   0.0%
1
  11.1%
2
  20.0%
0
   0.0%
Bloated, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
2
  16.7%
0
   0.0%
1
  20.0%
1
  11.1%
0
   0.0%
3
  30.0%
0
   0.0%
Burping, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
2
  20.0%
0
   0.0%
Passing gas or flatus, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
1
  20.0%
1
  11.1%
0
   0.0%
2
  20.0%
0
   0.0%
Constipation, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
3
  60.0%
4
  44.4%
3
  33.3%
0
   0.0%
0
   0.0%
Diarrhea, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
3
  33.3%
4
  44.4%
4
  40.0%
0
   0.0%
Loose stools, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
3
  60.0%
4
  44.4%
3
  33.3%
3
  30.0%
0
   0.0%
Hard stools, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Urgent need to have bowel movement, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
2
  40.0%
1
  11.1%
2
  22.2%
2
  20.0%
0
   0.0%
Sensatn not complete empty bowels, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
2
  22.2%
3
  33.3%
2
  20.0%
0
   0.0%
Abdominal pain, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Reflux syndrome, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Indigestion syndrome, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
2
  20.0%
0
   0.0%
Constipation syndrome, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Diarrhea syndrome, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
3
  33.3%
2
  22.2%
2
  20.0%
0
   0.0%
Overall GSRS, Day 7 Number Analyzed 12 participants 4 participants 5 participants 9 participants 9 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Pain/discomfort in upper abdomen, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
2
  40.0%
1
  11.1%
1
  12.5%
1
  10.0%
1
   7.7%
Heartburn, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 10 participants
1
   8.3%
0
   0.0%
2
  40.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Acid reflux, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Hunger pains, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
2
  22.2%
0
   0.0%
2
  20.0%
0
   0.0%
Nausea, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Rumbling, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
2
  40.0%
1
  11.1%
0
   0.0%
2
  20.0%
0
   0.0%
Bloated, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
2
  16.7%
1
  25.0%
2
  40.0%
1
  11.1%
0
   0.0%
3
  30.0%
00
   0.0%
Burping, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
1
  20.0%
0
   0.0%
0
   0.0%
2
  20.0%
0
   0.0%
Passing gas or flatus, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
1
  25.0%
2
  40.0%
2
  22.2%
0
   0.0%
2
  20.0%
0
   0.0%
Constipation, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
1
  25.0%
1
  20.0%
0
   0.0%
0
   0.0%
2
  20.0%
0
   0.0%
Diarrhea, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
4
  80.0%
3
  33.3%
2
  25.0%
5
  50.0%
0
   0.0%
Loose stools, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
3
  60.0%
2
  22.2%
3
  37.5%
3
  30.0%
0
   0.0%
Hard stools, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Urgent need to have bowel movement, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
1
  25.0%
4
  80.0%
2
  22.2%
3
  37.5%
3
  30.0%
0
   0.0%
Sensation not complete empty bowels, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
3
  60.0%
2
  22.2%
3
  37.5%
2
  20.0%
0
   0.0%
Abdominal pain, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Reflux syndrome, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
1
   8.3%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
Indigestion syndrome, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
1
  25.0%
1
  20.0%
1
  11.1%
0
   0.0%
2
  20.0%
0
   0.0%
Constipation syndrome, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
2
  40.0%
0
   0.0%
0
   0.0%
2
  20.0%
0
   0.0%
Diarrhea syndrome, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
3
  60.0%
2
  22.2%
1
  12.5%
3
  30.0%
0
   0.0%
Overall GSRS, Day 14 Number Analyzed 12 participants 4 participants 5 participants 9 participants 8 participants 10 participants 13 participants
0
   0.0%
0
   0.0%
1
  20.0%
1
  11.1%
0
   0.0%
2
  20.0%
0
   0.0%
15.Primary Outcome
Title Number of Participants With Fecal Occult Blood Monitoring for Symptomatic or Visible Gastrointestinal Bleeding or Asymptomatic Occult Bleeding
Hide Description Testing cards were provided to participants for assessments. Participants with abnormal not clinically significant and abnormal clinically significant is presented. The Day -1 sample was obtained any time starting Day -2 and prior to GSK2330672 dosing on Day 1. The Day 14 sample was collected any time after dosing on Day 14 and prior to discharge on Day 15.
Time Frame Up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID Run-in Only
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 13 5 5 9 9 10 13 6
Measure Type: Count of Participants
Unit of Measure: Participants
Abnormal not clinically significant
0
   0.0%
1
  20.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
  10.0%
1
   7.7%
0
   0.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
2
  33.3%
16.Secondary Outcome
Title PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-maximum Observed Concentration (Cmax)
Hide Description The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Statistics for geometric least square mean provided.
Time Frame Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population was used which was defined as participants from the safety population who had plasma metformin, sitagliptin, and/or GSK2330672 PK parameter estimates from any portion of the study. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 12 4 5 9 8 9 13
Geometric Least Squares Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter (ng/mL)
1102.2
(26.92%)
1289.3
(41.81%)
1219.9
(23.76%)
1160.0
(18.64%)
1378.8
(22.77%)
1376.6
(21.70%)
1223.5
(27.36%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.17
Confidence Interval (2-Sided) 90%
0.92 to 1.49
Estimation Comments Mean and confidence interval (CI) for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 90%
0.89 to 1.38
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 90%
0.87 to 1.27
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 90%
1.03 to 1.52
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 90%
1.04 to 1.50
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an analysis of variance (ANOVA) model of log-transformed values.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 90%
0.94 to 1.31
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
17.Secondary Outcome
Title PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-time of Occurrence of Cmax (Tmax)
Hide Description The time at which Cmax observed was determined directly from the raw concentration-time data.
Time Frame Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 12 4 5 9 8 9 13
Median (Full Range)
Unit of Measure: Hour
1.510
(1.00 to 4.00)
1.000
(1.00 to 1.50)
1.000
(0.50 to 3.98)
1.050
(1.00 to 1.50)
1.750
(0.50 to 4.00)
1.500
(1.00 to 4.00)
2.050
(1.00 to 4.02)
18.Secondary Outcome
Title PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-area Under the Concentration-time Curve Over the Dosing Interval of 10 Hours (AUC[0-10])
Hide Description PK population. Only those participants available at the specified time points were analyzed.
Time Frame Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK2330672 10 mg BID GSK2330672 20 mg BID GSK2330672 30 mg BID GSK2330672 60 mg BID GSK2330672 90 mg BID Sitagliptin 50 mg BID
Hide Arm/Group Description:
Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Overall Number of Participants Analyzed 12 4 5 9 8 9 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour×ng/mL
6805.8
(19.70%)
5982.0
(34.72%)
7066.2
(25.80%)
7066.5
(16.09%)
8090.5
(33.06%)
8375.3
(32.78%)
8425.4
(28.11%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 10 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an ANOVA model following log-transformation.
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 90%
0.68 to 1.13
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 20 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an ANOVA model following log-transformation.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 90%
0.82 to 1.31
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 30 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an ANOVA model following log-transformation.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 90%
0.85 to 1.26
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 60 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an ANOVA model following log-transformation.
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.19
Confidence Interval (2-Sided) 90%
0.97 to 1.45
Estimation Comments Mean and CI for the difference in least squares means (Active-Placebo) are back-transformed to form the point estimate and associated CI for the ratio of geometric means.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2330672 90 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments Each GSK2330672 dose level was compared to placebo using an ANOVA model following log-transformation.
Method of Estimation Estimation Parameter