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A 6-Week Study Of PF-05175157 In Type 2 Diabetes Mellitus

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: NCT01792635
Recruitment Status : Terminated (The study was terminated prematurely on 16 May 2014 due to a safety concern.)
First Posted : February 15, 2013
Results First Posted : February 16, 2017
Last Update Posted : February 16, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Basic Science
Condition Diabetes Mellitus, Type 2
Interventions Drug: PF-05175157
Drug: Placebo
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Participants in Part A Placebo - Part B PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min. Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Period Title: Part A
Started 6 0 0
Completed 6 0 0
Not Completed 0 0 0
Period Title: Part B
Started 0 6 7
Completed 0 2 3
Not Completed 0 4 4
Reason Not Completed
Adverse Event             0             0             1
Study terminated             0             4             3
Arm/Group Title All Participants in Part A Placebo - Part B PF-05175157 200 mg Twice a Day - Part B Total
Hide Arm/Group Description Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min. Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 6 6 7 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 7 participants 19 participants
50.7  (9.5) 49.3  (9.2) 55.1  (4.6) 51.9  (7.9)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 7 participants 19 participants
Male 5 5 5 15
Female 1 1 2 4
1.Primary Outcome
Title Glucose Infusion Rates (GIR) in Part A
Hide Description GIR obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. Assessment of whole body insulin sensitivity was performed during the steady states of the low insulin infusion rate (ie, Step 1) and during the steady state of the high insulin infusion rate (ie, Step 2). These indices were called GIR1 and GIR2, respectively.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
Arm/Group Title All Participants in Part A
Hide Arm/Group Description:
Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min.
Overall Number of Participants Analyzed 6
Mean (90% Confidence Interval)
Unit of Measure: mg/min
Clamp 1 GIR1
191
(153 to 229)
Clamp 1 GIR2
780
(580 to 980)
Clamp 2 GIR1
152
(132 to 172)
2.Primary Outcome
Title Endogenous Gucose Production (EGP) in Part A
Hide Description EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2). Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. EGP was measured under basal conditions; then during the low dose insulin infusion EGP was partially suppressed (hepatic insulin sensitivity), while during the high dose insulin infusion, EGP was almost completely suppressed and peripheral glucose uptake was maximally stimulated (peripheral insulin sensitivity).
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
Arm/Group Title All Participants in Part A
Hide Arm/Group Description:
Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: mg/kilogram (kg) body weight (BW)/min
Clamp 1 EGP0
1.79
(1.48 to 1.99)
Clamp 1 EGP1
0.85
(0.51 to 0.98)
Clamp 1 EGP2
0.07
(-0.02 to 0.36)
Clamp 2 EGP0
1.68
(1.59 to 1.89)
Clamp 2 EGP1
0.81
(0.71 to 0.98)
3.Primary Outcome
Title [6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A
Hide Description [6,6-2H2] PGE was the molar fraction of labeled glucose measured in plasma. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and who had at least one euglycemic hyperinsulinemic clamp
Arm/Group Title All Participants in Part A
Hide Arm/Group Description:
Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min.
Overall Number of Participants Analyzed 6
Mean (90% Confidence Interval)
Unit of Measure: percentage enrichment of plasma glucose
Clamp 1
2.96
(2.94 to 2.98)
Clamp 2
2.97
(2.88 to 3.06)
4.Primary Outcome
Title Rate of Appearance of Glucose (Ra) in Part A
Hide Description Rate of appearance of glucose (Ra) in fasting state and during insulin infusions (Step 1 and Step 2).
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
Arm/Group Title All Participants in Part A
Hide Arm/Group Description:
Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min.
Overall Number of Participants Analyzed 6
Mean (Full Range)
Unit of Measure: mg/kg BW/min
Clamp 1 Step 1
3.575
(2.74 to 4.41)
Clamp 1 Step 2
14.829
(9.90 to 19.76)
Clamp 2 Step 1
2.859
(2.24 to 3.47)
5.Primary Outcome
Title Whole-body Glucose Uptake in Part A
Hide Description Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized and who had at least one euglycemic hyperinsulinemic clamp.
Arm/Group Title All Participants in Part A
Hide Arm/Group Description:
Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min.
Overall Number of Participants Analyzed 6
Mean (90% Confidence Interval)
Unit of Measure: mg/kg BW/min
14.829
(9.90 to 19.76)
6.Primary Outcome
Title Whole-body Glucose Uptake in Part B in Placebo Group
Hide Description Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title Placebo - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6
Mean (Full Range)
Unit of Measure: mg/kg BW/min
Step 2 Value 1
4.245
(4.18 to 4.41)
Step 2 Value 2
6.325
(6.26 to 6.45)
Step 2 Value 3
2.793
(2.72 to 2.85)
Step 2 Value 4
6.835
(6.56 to 7.38)
Step 2 Value 5
4.400
(3.97 to 5.23)
Step 2 Value 6
3.940
(3.86 to 3.98)
Step 2 Value 7
4.553
(4.37 to 4.62)
Step 2 Value 8
4.225
(4.16 to 4.40)
7.Primary Outcome
Title Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group
Hide Description Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: mg/kg BW/min
Step 2 Value 1
3.775
(3.70 to 3.83)
Step 2 Value 2
9.033
(8.95 to 9.08)
Step 2 Value 3
8.903
(8.33 to 9.37)
Step 2 Value 4
11.310
(11.13 to 11.47)
Step 2 Value 5
4.133
(3.98 to 4.50)
Step 2 Value 6
6.763
(5.98 to 7.93)
Step 2 Value 7
8.243
(8.06 to 8.73)
Step 2 Value 8
7.180
(7.03 to 7.39)
Step 2 Value 9
10.113
(9.80 to 10.28)
Step 2 Value 10
6.205
(6.16 to 6.31)
8.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B
Hide Description An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were admitted to the clinical research unit (CRU) on Day -5
Arm/Group Title Placebo - Part B PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Unit of Measure: Participants
Participants w ith AEs 1 5
Participants w ith SAEs 0 1
Participants discontinued due to AEs 0 1
9.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities in Part B
Hide Description Number of participants with laboratory test abnormalities without regard to baseline abnormality. The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and creatine phosphokinase); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, and microscopy); others (follicle stimulating hormone [FSH], urine drug screen, lipid profile and very-low-density lipoproteins [VLDL], hemoglobin A1c [HbA1c], C-peptide, thyroid-stimulating hormone [TSH], Hepatitis B and C, human immunodeficiency virus [HIV], triglycerides, urine creatinine).
Time Frame Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were admitted to the Clinical Research Unit (CRU) on Day -5
Arm/Group Title Placebo - Part B PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Unit of Measure: Participants
6 7
10.Primary Outcome
Title Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B
Hide Description Criteria for potentially clinical important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of less than (<) 90 millimeters of mercury (mm Hg) or change in sitting SBP of greater or equal to (>=)30 mm Hg, sitting diastolic blood pressure (DBP) of <50 mm Hg or change in sitting DBP of >=20 mm Hg, sitting pulse rate of <40 or greater than (>) 120 beats per minute (bpm).
Time Frame Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were admitted to the CRU on Day -5
Arm/Group Title Placebo - Part B PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Unit of Measure: Participants
SBP <90 mm Hg 0 0
DBP <50 mm Hg 0 0
Pulse Rate <40 bpm 0 0
Pulse Rate >120 bpm 0 0
SBP maximum increase from baseline >=30 mm Hg 0 0
DBP maximum increase from baseline >=20 mm Hg 0 0
SBP maximum decrease from baseline >=30 mm Hg 0 1
DBP maximum decrease from baseline >=20 mm Hg 0 0
11.Primary Outcome
Title Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B
Hide Description Criteria for PCI changes in ECG (12-lead) were defined as: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval) >=300 milliseconds (msec) and increase of >=25% from baseline when baseline >200 msec or increase of >=50% when baseline less than or equal to (<=) 200 msec; the time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS interval) >=140 msec and increase of >=50% from baseline; the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT), corrected for heart rate (QTc) using the Fridericia formula (QTcF) of 450 to < 480 msec and >=480 msec, or an increase from baseline of 30 to <60 msec or >=60 msec.
Time Frame Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were admitted to the CRU on Day -5.
Arm/Group Title Placebo - Part B PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Unit of Measure: Participants
QTc increase from Baseline of >=60 msec 0 1
QTcF increase from Baseline of >=60 msec 0 1
12.Secondary Outcome
Title GIR in Part B in Placebo Group
Hide Description Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title Placebo - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6
Mean (Full Range)
Unit of Measure: mg/min
GIR1 Value 1
139.4
(0 to 150)
GIR1 Value 2
178.3
(176 to 246)
GIR1 Value 3
52.4
(0 to 97)
GIR1 Value 4
196.5
(181 to 197)
GIR1 Value 5
145.7
(92 to 161)
GIR1 Value 6
104.7
(103 to 140)
GIR1 Value 7
154.7
(143 to 218)
GIR1 Value 8
85.4
(68 to 86)
GIR2 Value 1
413.9
(411 to 461)
GIR2 Value 2
645.0
(645 to 645)
GIR2 Value 3
293.4
(217 to 296)
GIR2 Value 4
668.2
(610 to 711)
GIR2 Value 5
400.4
(368 to 504)
GIR2 Value 6
359.3
(289 to 363)
GIR2 Value 7
338.0
(338 to 338)
GIR2 Value 8
343.3
(322 to 344)
13.Secondary Outcome
Title GIR in Part B in PF-05175157 200 mg BID Group
Hide Description Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: mg/min
GIR1 Value 1
170.5
(118 to 191)
GIR1 Value 2
425.0
(367 to 427)
GIR1 Value 3
334.2
(311 to 335)
GIR1 Value 4
409.3
(277 to 521)
GIR1 Value 5
50.0
(50 to 50)
GIR1 Value 6
160.9
(160 to 188)
GIR1 Value 7
113.2
(68 to 116)
GIR1 Value 8
157.7
(113 to 225)
GIR1 Value 9
215.2
(201 to 236)
GIR1 Value 10
159.9
(159 to 178)
GIR2 Value 1
359.2
(270 to 368)
GIR2 Value 2
896.5
(871 to 921)
GIR2 Value 3
896.3
(864 to 1064)
GIR2 Value 4
1078.5
(1068 to 1079)
GIR2 Value 5
357.6
(357 to 370)
GIR2 Value 6
564.0
(520 to 656)
GIR2 Value 7
693.1
(666 to 728)
GIR2 Value 8
647.2
(623 to 681)
GIR2 Value 9
889.4
(821 to 893)
GIR2 Value 10
519.5
(512 to 540)
14.Secondary Outcome
Title EGP in Part B in Placebo Group
Hide Description EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title Placebo - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: mg/kg fat free mass (FFM)/min
EGP0 Value 1
1.540
(1.49 to 1.60)
EGP0 Value 2
1.690
(1.64 to 1.75)
EGP0 Value 3
1.285
(1.24 to 1.33)
EGP0 Value 4
1.575
(1.55 to 1.62)
EGP0 Value 5
1.965
(1.89 to 2.04)
EGP0 Value 6
1.538
(1.50 to 1.58)
EGP0 Value 7
1.518
(1.47 to 1.56)
EGP0 Value 8
1.518
(1.49 to 1.56)
EGP1 Value 1
0.600
(0.57 to 0.66)
EGP1 Value 2
0.585
(0.55 to 0.61)
EGP1 Value 3
0.525
(0.49 to 0.59)
EGP1 Value 4
0.500
(0.49 to 0.52)
EGP1 Value 5
0.808
(0.75 to 0.86)
EGP1 Value 6
0.830
(0.82 to 0.84)
EGP1 Value 7
0.560
(0.55 to 0.58)
EGP1 Value 8
0.825
(0.78 to 0.85)
EGP2 Value 1
0.200
(0.17 to 0.22)
EGP2 Value 2
-0.063
(-0.09 to -0.03)
EGP2 Value 3
-0.050
(-0.10 to -0.01)
EGP2 Value 4
0.280
(0.25 to 0.31)
EGP2 Value 5
0.145
(0.06 to 0.23)
EGP2 Value 6
0.223
(0.20 to 0.24)
EGP2 Value 7
0.180
(0.17 to 0.19)
EGP2 Value 8
0.405
(0.38 to 0.46)
15.Secondary Outcome
Title EGP in Part B in PF-05175157 200 mg BID Group
Hide Description EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: mg/kg fat free mass (FFM)/min
EGP0 Value 1
1.240
(1.23 to 1.27)
EGP0 Value 2
1.445
(1.42 to 1.46)
EGP0 Value 3
2.083
(2.03 to 2.15)
EGP0 Value 4
1.708
(1.68 to 1.73)
EGP0 Value 5
1.695
(1.67 to 1.72)
EGP0 Value 6
1.615
(1.59 to 1.65)
EGP0 Value 7
1.690
(1.64 to 1.75)
EGP0 Value 8
1.393
(1.25 to 1.46)
EGP0 Value 9
1.448
(1.43 to 1.46)
EGP0 Value 10
1.345
(1.33 to 1.36)
EGP1 Value 1
0.568
(0.54 to 0.59)
EGP1 Value 2
0.250
(0.22 to 0.28)
EGP1 Value 3
0.788
(0.69 to 0.89)
EGP1 Value 4
0.575
(0.54 to 0.62)
EGP1 Value 5
1.183
(1.12 to 1.22)
EGP1 Value 6
0.538
(0.52 to 0.55)
EGP1 Value 7
0.765
(0.74 to 0.78)
EGP1 Value 8
0.555
(0.53 to 0.58)
EGP1 Value 9
0.193
(0.11 to 0.23)
EGP1 Value 10
0.418
(0.35 to 0.45)
EGP2 Value 1
0.253
(0.23 to 0.29)
EGP2 Value 2
0.165
(0.09 to 0.21)
EGP2 Value 3
-0.035
(-0.43 to 0.14)
EGP2 Value 4
0.243
(0.10 to 0.39)
EGP2 Value 5
0.543
(0.47 to 0.67)
EGP2 Value 6
0.110
(0.03 to 0.15)
EGP2 Value 7
0.190
(0.15 to 0.24)
EGP2 Value 8
-0.313
(-0.42 to -0.23)
EGP2 Value 9
-0.253
(-0.34 to -0.20)
EGP2 Value 10
0.198
(0.19 to 0.21)
16.Secondary Outcome
Title Ra in Part B in Placebo Group
Hide Description Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title Placebo - Part B
Hide Arm/Group Description:
Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 6
Mean (Full Range)
Unit of Measure: mg/kg BW/min
Step 2 Value 1
4.245
(4.18 to 4.41)
Step 2 Value 2
6.325
(6.26 to 6.45)
Step 2 Value 3
2.793
(2.72 to 2.85)
Step 2 Value 4
6.835
(6.56 to 7.38)
Step 2 Value 5
4.400
(3.97 to 5.23)
Step 2 Value 6
3.940
(3.86 to 3.98)
Step 2 Value 7
4.553
(4.37 to 4.62)
Step 2 Value 8
4.225
(4.16 to 4.40)
17.Secondary Outcome
Title Ra in Part B in PF-05175157 200 mg BID Group
Hide Description Ra in fasting state and during insulin infusions (Step 1 and Step 2).
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Part B of the study was terminated due to the safety issue. Due to the limited participant number who completed study there no summary statistics were done by dosing regimen for Part B.
Arm/Group Title PF-05175157 200 mg Twice a Day - Part B
Hide Arm/Group Description:
Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
Overall Number of Participants Analyzed 7
Mean (Full Range)
Unit of Measure: mg/kg BW/min
Step 2 Value 1
3.775
(3.70 to 3.83)
Step 2 Value 2
9.033
(8.95 to 9.08)
Step 2 Value 3
8.903
(8.33 to 9.37)
Step 2 Value 4
11.310
(11.13 to 11.47)
Step 2 Value 5
4.133
(3.98 to 4.50)
Step 2 Value 6
6.763
(5.98 to 7.93)
Step 2 Value 7
8.243
(8.06 to 8.73)
Step 2 Value 8
7.180
(7.03 to 7.39)
Step 2 Value 9
10.113
(9.80 to 10.28)
Step 2 Value 10
6.205
(6.16 to 6.31)
Time Frame Baseline up to follow-up (up to approximately 3 days after the last clamp procedure in Part A and up to approximately 10 to 14 days after the last study drug administration in Part B)
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title All Participants in Part A PF-05175157 200 mg Twice a Day - Part B Placebo - Part B
Hide Arm/Group Description Participants underwent 2 step euglycemic hyperinsulinemic clamp procedure and were infused with insulin according to a specified algorithm to reduce plasma glucose levels to approximately 100 milligram (mg)/deciliter (dL). In Step 1 of the clamp, each individual’s insulin infusion rate during the last 2 hours of the overnight infusion was increased by 10 mU/square meter (m^2)/minute (min). During Step 2, all participants received an insulin infusion, at a rate of 120 mU/m^2/min. Participants received PF-05175157 200 mg twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks. Participants received placebo twice a day at approximately 08:00 immediately before the morning meal, and at approximately 18:00 before the dinner meal. The treatment period was 6 weeks.
All-Cause Mortality
All Participants in Part A PF-05175157 200 mg Twice a Day - Part B Placebo - Part B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
All Participants in Part A PF-05175157 200 mg Twice a Day - Part B Placebo - Part B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   1/7 (14.29%)   0/6 (0.00%) 
Blood and lymphatic system disorders       
Thrombocytopenia * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants in Part A PF-05175157 200 mg Twice a Day - Part B Placebo - Part B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   5/7 (71.43%)   1/6 (16.67%) 
Eye disorders       
Lacrimation increased * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Gastrointestinal disorders       
Constipation * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Infections and infestations       
Upper respiratory tract infection * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Hyperglycaemia * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders       
Blister * 1  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%) 
Pruritus * 1  0/6 (0.00%)  1/7 (14.29%)  1/6 (16.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.0
Part B of the study was terminated due to the safety issue. Due to the low number of participants who completed the study, there are no conclusions for PK or PD in Part B. The prioritization of Part A endpoints was done by inputs from team.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClnicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01792635    
Other Study ID Numbers: B1731003
First Submitted: December 20, 2012
First Posted: February 15, 2013
Results First Submitted: January 11, 2016
Results First Posted: February 16, 2017
Last Update Posted: February 16, 2017