Safety and Efficacy Study of Albiglutide in Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine whether albiglutide is effective in the treament of patients with type 2 diabetes.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of Two Dose Levels of Albiglutide Compared With Placebo in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Biological: albiglutide
* Biological: albiglutide uptitration
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes BMI 20-45kg/m2 inclusive Exclusion Criteria: females who are pregnant, lactating, or <6 weeks post-partum CHF NYHA class III-IV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: albiglutide<br>albiglutide weekly injection | Biological: albiglutide<br>* albiglutide weekly injection<br>|
| Placebo Comparator: placebo<br>albiglutide matching placebo | Biological: placebo<br>* matching albiglutide placebo weekly injection<br>|
| Experimental: albiglutide up-titration<br>albiglutide weekly injection uptitration at week 12 | Biological: albiglutide uptitration<br>* albiglutide uptitration at week 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 | Glycated hemoglobin (HbA1c) is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 52 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate. The last observation carried forward (LOCF) method was used to impute missing post-BL HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Weeks 104 and 156 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline and Weeks 104 and 156 | 
| Time to Hyperglycemia Rescue | Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: FPG >=280 milligrams/deciliter (mg/dL) between >=Week 2 and <Week 4; FPG >=250 mg/dL between >=Week 4 and <Week 12; HbA1c >=8.5% and a <=0.5% reduction from Baseline between >=Week 12 and <Week 24; HbA1c >=8.5% between >=Week 24 and <Week 48; HbA1c >=8.0% between >= Week 48 and <Week 156. Participants could have been rescued at any time on or after Week 2. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus 1 day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus 1 day for participants not requiring rescue. This time was divided by 7 to express the result in weeks. | From the start of study medication until the end of the treatment (up to Week 156) | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy. | Baseline and Week 52 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156 | The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline FPG minus the Baseline FPG. | Baseline and Week 156 | 
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 52) were assessed. | Week 52 | 
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 156) were assessed. | Week 156 | 
| Change From Baseline in Body Weight at Week 52 | The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy. | Baseline and Week 52 | 
| Change From Baseline in Body Weight at Week 156 | The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. | Baseline and Week 156 | 
| Change From Baseline in Postprandial Blood Glucose Profile Parameter-4 Hour C-peptide AUC | Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was 4 hour c-peptide AUC. The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline and Week 52 | 
| Change From Baseline in Postprandial Blood Glucose Profile Parameter- 4 Hour Blood Glucose AUC | Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was: 4 hour blood glucose area under urve AUC The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline and Week 52 | 
| Change From Baseline in Postprandial Blood Glucose Profile Parameters-4 Hour Insulin AUC and 4 Hour Proinsulin AUC | Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameters analyzed were: 4-hour insulin AUC (4 hr Ins AUC), and 4-hour proinsulin AUC (4 hr pro-Ins AUC). The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline and Week 52 | 
| Albiglutide Plasma Concentration at Weeks 8 and 24 | Albiglutide plasma concentration data was analyzed at Week 8 pre-dose, Week 8 post dose, Week 24 pre-dose and Week 24 post-dose. All participants who received albiglutide were initiated on a 30mg weekly dosing regimen; however, beginning at Week 12, participants in the albiglutide 50 mg treatment group were uptitrated to receive albiglutide 50 mg for the remainder of the study. | Weeks 8 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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placebo, albiglutide, monotherapy, diabetes