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Trial record 61 of 1031 for:    Area Under Curve AND insulin

Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 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: NCT02284009
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : March 25, 2019
Last Update Posted : March 25, 2019
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 1
Interventions Biological: Albiglutide weekly injection
Biological: Placebo weekly injection
Biological: Insulin
Enrollment 67
Recruitment Details This was a multicenter study conducted at 29 sites in Europe (Spain 10, United Kingdom (UK) 9, Germany 4, France 3 and Italy 3). A total of 67 participants with New-onset type 1 diabetes mellitus (NOT1DM) were randomized.
Pre-assignment Details Study was terminated early as part of the decision to withdraw albiglutide for commercial reasons. Study stopped after 67 participants were randomized instead of 68 as per protocol. Impact of early termination was minimal and did not affect the interpretation of results.
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description Matching placebo was administered once weekly for 52 weeks by subcutaneous (sc) injection in the abdomen, thigh or upper arm region in addition to insulin. Albiglutide 30 milligram (mg) was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Period Title: Overall Study
Started 17 50
Completed 11 40
Not Completed 6 10
Reason Not Completed
Adverse Event             3             0
Lost to Follow-up             1             3
Physician Decision             0             2
Withdrawal by Subject             2             5
Arm/Group Title Placebo Albiglutide Total
Hide Arm/Group Description Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin. Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated). Total of all reporting groups
Overall Number of Baseline Participants 17 50 67
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 50 participants 67 participants
22.8  (3.83) 22.7  (3.72) 22.7  (3.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 50 participants 67 participants
Female
7
  41.2%
21
  42.0%
28
  41.8%
Male
10
  58.8%
29
  58.0%
39
  58.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 50 participants 67 participants
Black or African American
0
   0.0%
1
   2.0%
1
   1.5%
White
17
 100.0%
49
  98.0%
66
  98.5%
1.Primary Outcome
Title Mean Change From Baseline in Time Normalized Stimulated (From Mixed Meal Tolerance Test [MMTT]) 2-hour Plasma C-peptide Area Under the Curve (AUC) at Week 52
Hide Description Participants (parts) had a balanced diet consistent with dietitian’s advice and made no major changes in exercise regimens. Evening before the MMTT, participants had a full meal then fasted from 9 post meridiem (pm) until MMTT was completed. Water, black coffee or tea without sugar or artificial sweeteners was allowed. Plasma glucose was measured prior to the finger-stick test and MMTT was performed only if in range > 3.9 millimoles per liter (mmol/L) [70 mg/deciliter (dL)] and <= 11.1 mmol/L (200 mg/dL). Baseline was defined as the last non-missing value with assessment date on or before the 1st day of study medication. Change from Baseline was calculated by subtracting Baseline value from Week 52 value. Intent-to-treat (ITT) Population comprised of all randomly assigned participants who received at least 1 dose of study medication with at least 1 post-Baseline assessment of the primary endpoint.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data at the specified time points were analyzed. Time normalized plasma C-peptide AUC was calculated using trapezoidal rule then dividing by 120 (if the result at t=120 is non-missing otherwise the time difference between first and last times with non-missing results is used)
Arm/Group Title Placebo Albiglutide DEFEND-1 Placebo
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Historical placebo data from the DEFEND-1 (NCT00678886) study was used as prior knowledge.
Overall Number of Participants Analyzed 11 40 53
Mean (Standard Deviation)
Unit of Measure: Nanomoles per liter
-0.16  (0.366) -0.13  (0.244) -0.27  (0.314)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.00 to 0.24
Estimation Comments Analysis was performed using a Bayesian model incorporating historical placebo data using a robust mixture prior. Values above are 95% credible intervals. Probability of treatment difference (Albiglutide – Placebo) >= 0.2 nmol/L = 0.097.
2.Secondary Outcome
Title Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64
Hide Description Participants had a balanced diet consistent with dietitian’s advice and made no major changes in exercise regimens. On the evening before the MMTT, participants had a full meal and then fasted from 9 pm until the MMTT was completed. Water, black coffee or tea without sugar or artificial sweeteners was allowed. Plasma glucose was measured prior to the test using a finger-stick test and MMTT was performed only if it was in range > 3.9 mmol/L (70 mg/dL) and <= 11.1 mmol/L (200 mg/dL). Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline and Weeks 16, 28 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only parts with data available at specified data points were analyzed (represented by n= X in the category titles).Time normalized plasma C-peptide AUC was calculated using trapezoidal rule then dividing by 120 (if result at t=120 is non-missing otherwise time difference between first and last times with non-missing results is used)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Nanomoles per liter
Week 16, n=15,44 Number Analyzed 15 participants 44 participants
0.00  (0.216) 0.07  (0.234)
Week 28, n=13,41 Number Analyzed 13 participants 41 participants
-0.14  (0.177) 0.01  (0.225)
Week 64, n=11,36 Number Analyzed 11 participants 36 participants
-0.22  (0.277) -0.22  (0.246)
3.Secondary Outcome
Title Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64
Hide Description Maximum stimulated plasma C-peptide was the highest value at any time point during the 2 hour MMTT after the participant has ingested the mixed meal at Baseline, Week 16, Week 28, Week 52 and Week 64. Blood samples were taken to assess levels of C-peptide at: 10 minutes before Time 0 (-10 minutes), Immediately before the participant starts drinking the nutritional drink (Time 0) and 15, 30, 60, 90, and 120 minutes after Time 0.
Time Frame Baseline and Weeks 16, 28, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Nanomoles per liter
Baseline, n=15,46 Number Analyzed 15 participants 46 participants
0.86  (0.382) 0.82  (0.448)
Week 16, n=15,45 Number Analyzed 15 participants 45 participants
0.84  (0.481) 1.02  (0.558)
Week 28,n=13,42 Number Analyzed 13 participants 42 participants
0.68  (0.442) 0.91  (0.594)
Week 52,n=11,41 Number Analyzed 11 participants 41 participants
0.63  (0.516) 0.69  (0.479)
Week 64, n=11,37 Number Analyzed 11 participants 37 participants
0.58  (0.453) 0.48  (0.363)
4.Secondary Outcome
Title Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64
Hide Description Blood samples were taken to assess levels of glucagon at: 10 minutes before Time 0 (-10 minutes), immediately before the participant started drinking the nutritional drink (Time 0) and 15, 30, 60, 90, and 120 minutes after Time 0. Mean change from Baseline in time normalized plasma glucagon AUC (from MMTT) at Week 16, 28, 52 and 64 was reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline and Weeks 16, 28, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only parts with data available at specified data points were analyzed (represented by n= X in the category titles). Time normalized plasma glucagon AUC was calculated using trapezoidal rule then dividing by 120 (if result at t=120 is non-missing otherwise time difference between first and last times with non-missing results is used)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Nanograms per liter
Week 16,n=15,45 Number Analyzed 15 participants 45 participants
-2.28  (11.221) -1.10  (4.496)
Week 28,n=13,43 Number Analyzed 13 participants 43 participants
-2.97  (11.574) 3.91  (22.197)
Week 52,n=11,40 Number Analyzed 11 participants 40 participants
-0.31  (15.989) 4.66  (13.628)
Week 64,n=11,37 Number Analyzed 11 participants 37 participants
3.19  (18.279) 8.82  (17.650)
5.Secondary Outcome
Title Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64
Hide Description Responders were defined as participants achieving glycosylated hemoglobin A1c (HbA1c) <= 7.0 percent and mean daily insulin use < 0.5 units per kilograms (kg) per day. Percentages are based on the number of participants with available HbA1c and insulin use data in each treatment group at that visit.
Time Frame Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline, n=15, 46 Number Analyzed 15 participants 46 participants
26.7 37.0
Week 4,n=14,42 Number Analyzed 14 participants 42 participants
71.4 78.6
Week 8,n=14,46 Number Analyzed 14 participants 46 participants
85.7 67.4
Week 16,n=15,45 Number Analyzed 15 participants 45 participants
86.7 73.3
Week 28,n=12,42 Number Analyzed 12 participants 42 participants
75.0 73.8
Week 40,n=13,40 Number Analyzed 13 participants 40 participants
76.9 62.5
Week 52,n=12,41 Number Analyzed 12 participants 41 participants
41.7 48.8
Week 64,n=11,38 Number Analyzed 11 participants 38 participants
36.4 34.2
6.Secondary Outcome
Title Percentage of Participants Achieving Partial Remission Status (Insulin Dose-adjusted Hemoglobin A1c (IDAA1C)<= 9.0) at Baseline, Week 4, 8, 16, 28, 40, 52 and 64
Hide Description Participant achieving partial remission status was defined as a participant with IDAA1C <=9.0 . Percentages were based on the number of participants with available IDAA1c data in each treatment group at that visit.
Time Frame Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline, n= 15, 46 Number Analyzed 15 participants 46 participants
73.3 60.9
Week 4,n=14,42 Number Analyzed 14 participants 42 participants
92.9 88.1
Week 8,n=14,46 Number Analyzed 14 participants 46 participants
92.9 87.0
Week 16,n=15,45 Number Analyzed 15 participants 45 participants
86.7 86.7
Week 28,n=12,42 Number Analyzed 12 participants 42 participants
75.0 85.7
Week 40,n=13,40 Number Analyzed 13 participants 40 participants
84.6 82.5
Week 52,n=12,41 Number Analyzed 12 participants 41 participants
58.3 70.7
Week 64,n=11,38 Number Analyzed 11 participants 38 participants
54.5 55.3
7.Secondary Outcome
Title Change From Baseline in Percent HbA1c at Week 52
Hide Description Change from Baseline in percent HbA1c was reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the Week 52 value.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 12 43
Mean (Standard Deviation)
Unit of Measure: Percentage of HbA1c
-0.73  (1.033) -0.59  (1.649)
8.Secondary Outcome
Title Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64)
Hide Description Blood samples were collected from participants for analysis of HbA1c at indicated time points and percentage of HbA1c has been calculated for Weeks 4, 8, 16, 28, 40, 52 and 64.
Time Frame Weeks 4, 8, 16, 28, 40, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=x in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Percentage of HbA1c
Week 4,n=15,43 Number Analyzed 15 participants 43 participants
6.29  (0.688) 6.10  (0.725)
Week 8,n=15,46 Number Analyzed 15 participants 46 participants
5.91  (0.689) 5.82  (0.725)
Week 16,n=15,46 Number Analyzed 15 participants 46 participants
5.97  (0.801) 5.78  (0.733)
Week 28,n=13,43 Number Analyzed 13 participants 43 participants
6.03  (0.747) 6.00  (0.824)
Week 40,n=13,42 Number Analyzed 13 participants 42 participants
6.22  (0.860) 6.20  (0.894)
Week 52,n=12,43 Number Analyzed 12 participants 43 participants
6.56  (0.950) 6.58  (1.512)
Week 64,n=12,40 Number Analyzed 12 participants 40 participants
7.12  (1.335) 6.92  (1.176)
9.Secondary Outcome
Title Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64
Hide Description The mean daily insulin use value was calculated, in units/kg/day as the sum of average prandial insulin doses and average of basal insulin doses for each participant recorded daily for the 3 days prior to the specified visits, divided by the participant's body weight in kg. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Units/kg/day
Week 4,n=14,43 Number Analyzed 14 participants 43 participants
-0.02  (0.076) -0.03  (0.093)
Week 8,n=14,46 Number Analyzed 14 participants 46 participants
-0.04  (0.105) -0.02  (0.123)
Week 16,n=15,45 Number Analyzed 15 participants 45 participants
-0.05  (0.100) -0.01  (0.148)
Week 28,n=12,42 Number Analyzed 12 participants 42 participants
-0.01  (0.139) 0.03  (0.145)
Week 40,n=13,40 Number Analyzed 13 participants 40 participants
-0.01  (0.151) 0.03  (0.145)
Week 52,n=12,41 Number Analyzed 12 participants 41 participants
0.04  (0.119) 0.11  (0.215)
Week 64,n=11,38 Number Analyzed 11 participants 38 participants
0.04  (0.140) 0.10  (0.187)
10.Secondary Outcome
Title Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52
Hide Description Significant hypoglycemia was defined as an event with plasma glucose level <= 3.9 mmol/L (<= 70 mg/dL) and/or requiring third party intervention. This corresponds to American Diabetes Association (ADA) category definitions of severe, documented symptomatic, and asymptomatic hypoglycemia. The time period was defined as: > Week 24 to <= Week 52 = Day 169 to Day 364. Number of Events were defined as the total number of significant hypoglycemic events at each level of summarization. Number of events of hypoglycemia with confirmed self plasma glucose monitoring <=3.9 mmol/L and/or requiring third party intervention (i.e., severe, documented symptomatic and asymptomatic hypoglycemic events) occurring >Week 24 and <=Week 52 are presented.
Time Frame Week 24 to 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data at specified time points were analyzed
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 13 45
Measure Type: Number
Unit of Measure: Hypoglycemic events
Any Significant Hypoglycemia 472 1592
Severe Hypoglycemia 0 0
Documented Symptomatic Hypoglycemia 241 996
Asymptomatic Hypoglycemia 231 596
11.Secondary Outcome
Title Time Spent With Plasma Glucose Level <= 3.9, > 3.9 to <= 10.0, and > 10.0 Measured by 72 Hour Continuous Glucose Monitoring (CGM) at Baseline, Week 28 and 52
Hide Description Three days before the visit, the participants made an additional visit to the study site to have the CGM fitted/inserted. It was worn for 3 consecutive days and was removed at the scheduled study visit. Whilst wearing the CGM, participants continued to monitor their plasma glucose at least 4 times a day and on one of the days, conducted 7-point glucose profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime). Time spent with a plasma glucose <=3.9 millimoles per liter (mmol/L), between >3.9 and 10.0 mmol/L, and >10.0 mmol/L, respectively as performed by 72-hour CGM at Baseline, Week 28 and Week 52 was reported.
Time Frame Baseline and Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available data at the specified time points were analysed (represented by n=X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: hours per day
<= 3.9 mmol/L, Baseline,n=14,42 Number Analyzed 14 participants 42 participants
0.80  (1.251) 0.98  (1.400)
<= 3.9 mmol/L, Week 28,n=12,36 Number Analyzed 12 participants 36 participants
1.72  (1.248) 1.38  (1.808)
<= 3.9 mmol/L, Week 52,n=10,31 Number Analyzed 10 participants 31 participants
1.60  (2.142) 1.36  (2.405)
> 3.9 to <= 10.0 mmol/L,Baseline,n=14,42 Number Analyzed 14 participants 42 participants
20.14  (3.675) 19.11  (3.732)
> 3.9 to <= 10.0 mmol/L,Week 28,n=12,36 Number Analyzed 12 participants 36 participants
18.93  (3.452) 18.83  (4.009)
> 3.9 to <= 10.0 mmol/L,Week 52,n=10,31 Number Analyzed 10 participants 31 participants
17.98  (4.491) 18.19  (4.772)
> 10.0 mmol/L, Baseline,n=14,42 Number Analyzed 14 participants 42 participants
3.06  (3.560) 3.90  (3.727)
> 10.0 mmol/L,Week 28,n=12,36 Number Analyzed 12 participants 36 participants
3.35  (3.115) 3.79  (3.782)
> 10.0 mmol/L,Week 52,n=10,31 Number Analyzed 10 participants 31 participants
4.42  (4.597) 4.45  (4.781)
12.Secondary Outcome
Title Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Hide Description A hypoglycemic excursion was defined as an occurrence where the plasma glucose level <=3.9 mmol/L (<=70 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hypoglycemic excursions were included. Number of Hypoglycemic Excursions for each participant from 7-Point Glucose Profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime) were reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Time Frame Baseline and Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants, as defined in the Measure Description were analysed (represented by n=X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Hypoglycemic excursions
Bseline,n=15,42 Number Analyzed 15 participants 42 participants
0.40  (0.632) 0.36  (0.656)
Week 28,n=13,40 Number Analyzed 13 participants 40 participants
0.31  (0.630) 0.28  (0.554)
Week 52,n=12,40 Number Analyzed 12 participants 40 participants
0.25  (0.452) 0.40  (0.672)
13.Secondary Outcome
Title Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Hide Description A hypoglycemic excursion was defined as an occurrence where the plasma glucose level <=3.9 mmol/L (<= 70 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hypoglycemic excursions were included. Greatest hypoglycemic excursion was calculated as 3.9 mmol/L minus the lowest recorded glucose level during the 7-point glucose profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime). If a participant had data recorded at that visit, but did not have a value <= 3.9 mmol/L, their greatest hypoglycemic excursion were 0 mmol/L for that visit. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Time Frame Baseline and Weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants, as defined in the Measure Description were analysed (represented by n=X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline,n=15,42 Number Analyzed 15 participants 42 participants
0.24  (0.470) 0.22  (0.597)
Week 28,n=13,40 Number Analyzed 13 participants 40 participants
0.18  (0.359) 0.08  (0.231)
Week 52,n=12,40 Number Analyzed 12 participants 40 participants
0.22  (0.484) 0.17  (0.393)
14.Secondary Outcome
Title Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Hide Description A hyperglycemic excursion is defined as an occurrence where the plasma glucose level > 10.0 mmol/L (> 180 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hyperglycemic excursions were included. Number of Hyperglycemic Excursions for each participant from 7-Point Glucose Profile (Before breakfast, 2 hours after breakfast, Before lunch, 2 hours after lunch, Before dinner, 2 hours after dinner, At bedtime) were reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Time Frame Baseline and Weeks 28 and 52
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Hide Analysis Population Description
ITT Population. Only evaluable participants, as defined in the Measure Description were analysed (represented by n=X in the category titles).
Arm/Group Title Placebo Albiglutide
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Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: Hyperglycemic excursions
Baseline,n=15,43 Number Analyzed 15 participants 43 participants
0.80  (1.014) 1.53  (1.502)
Week 28,n=13,40 Number Analyzed 13 participants 40 participants
1.23  (1.301) 0.73  (0.933)
Week 52,n=12,40 Number Analyzed 12 participants 40 participants
1.17  (1.115) 1.30  (1.522)
15.Secondary Outcome
Title Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52
Hide Description A hyperglycemic excursion is defined as an occurrence where the plasma glucose level > 10.0 mmol/L (> 180 mg/dL). At each visit, only evaluable participants, defined as those with >= 4 non-missing glucose values or >= 1 hyperglycemic excursions were included. Greatest hyperglycemic excursion was calculated as the largest recorded glucose level during the 7-point glucose profile (before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, at bedtime) minus 10.0 mmol/L. If a participant had data recorded at that visit, but does not have a value > 10.0 mmol/L, their greatest hyperglycemic excursion would be 0 mmol/L for that visit. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication.
Time Frame Baseline and weeks 28 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants, as defined in the Measure Description were analysed (represented by n=X in the category titles).
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline,n=15,43 Number Analyzed 15 participants 43 participants
0.94  (1.805) 2.72  (3.466)
Week 28,n=13,40 Number Analyzed 13 participants 40 participants
2.05  (2.154) 1.52  (2.493)
Week 52,n=12,40 Number Analyzed 12 participants 40 participants
2.19  (2.823) 2.42  (3.042)
16.Secondary Outcome
Title Change From Baseline in Body Weight (Kilograms) at Week 52
Hide Description Change from Baseline in body weight of participants was reported. Baseline was defined as the last non-missing value with an assessment date on or before the first day of study medication. Change from Baseline was calculated by subtracting the Baseline value from the Week 52 value.
Time Frame Baseline and Week 52
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Hide Analysis Population Description
ITT Population. Only those participants with available data at the specified time points were analyzed.
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 12 43
Mean (Standard Deviation)
Unit of Measure: Kilograms
0.26  (2.738) 0.77  (3.504)
17.Secondary Outcome
Title Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
Hide Description Body weight was measured in kilograms for participants at indicated time points.
Time Frame Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64
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Hide Analysis Population Description
ITT Population. Only participants with available data at the specified time points were summarized
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin.
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 15 46
Mean (Standard Deviation)
Unit of Measure: kilograms
Week 2,n=15, 43 Number Analyzed 15 participants 43 participants
70.16  (14.087) 66.16  (11.944)
Week 4,n=15, 44 Number Analyzed 15 participants 44 participants
69.87  (14.409) 66.39  (11.952)
Week 6,n=15, 46 Number Analyzed 15 participants 46 participants
69.83  (14.013) 65.65  (12.559)
Week 8,n=15, 46 Number Analyzed 15 participants 46 participants
70.08  (14.121) 65.32  (12.825)
Week 16,n=15, 46 Number Analyzed 15 participants 46 participants
69.40  (15.191) 65.41  (12.824)
Week 28,n=13, 43 Number Analyzed 13 participants 43 participants
66.08  (11.767) 65.32  (13.252)
Week 40,n=13, 42 Number Analyzed 13 participants 42 participants
66.08  (11.266) 66.20  (13.146)
Week 52,n=12, 43 Number Analyzed 12 participants 43 participants
66.86  (12.401) 66.80  (12.696)
Week 64,n=12, 40 Number Analyzed 12 participants 40 participants
68.29  (11.511) 68.13  (12.649)
18.Secondary Outcome
Title Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F]
Hide Description PK of Albiglutide was evaluated in participants using CL/F using PK samples collected on Weeks 4, 6, 8, 16. CL/F was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean body weights of 67 kilograms, and electronic glomerular filtration rate (eGFR) of 123 milliliters per minute.
Time Frame 48 hours after the most recent dose at Week 4, 6, 8 and 16
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PK population which comprised of participants in 'Safety Population' for whom a pharmacokinetic sample was obtained and analyzed. Only participants who received albiglutide were included in PK Population.
Arm/Group Title Albiglutide
Hide Arm/Group Description:
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 49
Mean (Standard Error)
Unit of Measure: Milliliters per hour
45.1  (2.56)
19.Secondary Outcome
Title Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F]
Hide Description PK of Albiglutide was evaluated in participants using V/F using PK samples collected on Weeks 4, 6, 8, 16. V/F was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean body weights of 67 kilograms, and eGFR of 123 milliliters per minute.
Time Frame 48 hours after the most recent dose at Week 4, 6, 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Albiglutide
Hide Arm/Group Description:
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 49
Mean (Standard Error)
Unit of Measure: Milliliters
4830  (677)
20.Secondary Outcome
Title Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka]
Hide Description PK of Albiglutide was evaluated in participants using Ka using PK samples collected on Weeks 4, 6, 8, 16. Ka was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 67 kilograms, and eGFR of 123 milliliters per minute.
Time Frame 48 hours after the most recent dose at Week 4, 6, 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Albiglutide
Hide Arm/Group Description:
Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
Overall Number of Participants Analyzed 49
Mean (Standard Error)
Unit of Measure: Per hour
0.0122  (0.0022)
Time Frame On-therapy AEs and SAEs were collected from start of study treatment up to 52-weeks
Adverse Event Reporting Description AEs and SAEs were summarized in Safety Population. Safety Population comprised of all participants who received at least one dose of study treatment.
 
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description Matching placebo was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region in addition to insulin. Albiglutide 30 mg was administered once weekly for 52 weeks by sc injection in the abdomen, thigh or upper arm region along with insulin (Dose increased to 50 mg once weekly at Week 6 if the 30 mg weekly dose was tolerated).
All-Cause Mortality
Placebo Albiglutide
Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)   0/50 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Albiglutide
Affected / at Risk (%) Affected / at Risk (%)
Total   2/17 (11.76%)   1/50 (2.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Uterine leiomyoma  1  0/17 (0.00%)  1/50 (2.00%) 
Psychiatric disorders     
Suicidal ideation  1  1/17 (5.88%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders     
Urticaria  1  1/17 (5.88%)  0/50 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Albiglutide
Affected / at Risk (%) Affected / at Risk (%)
Total   13/17 (76.47%)   37/50 (74.00%) 
Blood and lymphatic system disorders     
Anaemia  1  1/17 (5.88%)  3/50 (6.00%) 
Gastrointestinal disorders     
Nausea  1  5/17 (29.41%)  19/50 (38.00%) 
Diarrhoea  1  2/17 (11.76%)  13/50 (26.00%) 
Vomiting  1  4/17 (23.53%)  10/50 (20.00%) 
Abdominal distension  1  0/17 (0.00%)  7/50 (14.00%) 
Abdominal pain  1  0/17 (0.00%)  7/50 (14.00%) 
Abdominal pain upper  1  3/17 (17.65%)  4/50 (8.00%) 
Dyspepsia  1  0/17 (0.00%)  3/50 (6.00%) 
Flatulence  1  1/17 (5.88%)  2/50 (4.00%) 
Gastrointestinal pain  1  1/17 (5.88%)  1/50 (2.00%) 
General disorders     
Asthenia  1  2/17 (11.76%)  1/50 (2.00%) 
Injection site erythema  1  0/17 (0.00%)  3/50 (6.00%) 
Malaise  1  0/17 (0.00%)  3/50 (6.00%) 
Pyrexia  1  1/17 (5.88%)  1/50 (2.00%) 
Infections and infestations     
Nasopharyngitis  1  5/17 (29.41%)  13/50 (26.00%) 
Influenza  1  0/17 (0.00%)  4/50 (8.00%) 
Gastroenteritis  1  0/17 (0.00%)  3/50 (6.00%) 
Urinary tract infection  1  1/17 (5.88%)  2/50 (4.00%) 
Folliculitis  1  2/17 (11.76%)  0/50 (0.00%) 
Sinusitis  1  1/17 (5.88%)  1/50 (2.00%) 
Bronchitis  1  1/17 (5.88%)  0/50 (0.00%) 
Candida infection  1  1/17 (5.88%)  0/50 (0.00%) 
Laryngitis  1  1/17 (5.88%)  0/50 (0.00%) 
Paronychia  1  1/17 (5.88%)  0/50 (0.00%) 
Pharyngitis  1  1/17 (5.88%)  0/50 (0.00%) 
Tooth infection  1  1/17 (5.88%)  0/50 (0.00%) 
Varicella  1  1/17 (5.88%)  0/50 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/17 (5.88%)  6/50 (12.00%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  1/17 (5.88%)  0/50 (0.00%) 
Nervous system disorders     
Headache  1  5/17 (29.41%)  4/50 (8.00%) 
Carpal tunnel syndrome  1  1/17 (5.88%)  0/50 (0.00%) 
Dizziness  1  1/17 (5.88%)  0/50 (0.00%) 
Hypoaesthesia  1  1/17 (5.88%)  0/50 (0.00%) 
Somnolence  1  1/17 (5.88%)  0/50 (0.00%) 
Psychiatric disorders     
Depression  1  1/17 (5.88%)  0/50 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea  1  1/17 (5.88%)  0/50 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  0/17 (0.00%)  3/50 (6.00%) 
Cough  1  1/17 (5.88%)  0/50 (0.00%) 
Wheezing  1  1/17 (5.88%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders     
Eczema  1  1/17 (5.88%)  1/50 (2.00%) 
Lipodystrophy acquired  1  2/17 (11.76%)  0/50 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02284009     History of Changes
Other Study ID Numbers: 110933
First Submitted: September 18, 2014
First Posted: November 5, 2014
Results First Submitted: October 12, 2018
Results First Posted: March 25, 2019
Last Update Posted: March 25, 2019