A Study to Determine the Safety and Efficacy of Albiglutide in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of albiglutide in subjects with type 2 diabetes

Official Title
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A Randomized, Double-blind, Placebo and Active-Controlled, Parallel-group, Multicenter Study to Determine the Efficacy and Safety of Albiglutide Administered in Combination With Metformin and Glimepiride Compared With Metformin Plus Glimepiride and Placebo and With Metformin Plus Glimepiride and Pioglitazone in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: placebo to match albiglutide
* Biological: albiglutide
* Drug: metformin
* Drug: glimepiride
* Drug: pioglitazone
* Drug: placebo to match pioglitazone


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 less than 6 weeks post-partum current symptomatic heart failure (NYHA Class II-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 |
| --- | --- |
| Active Comparator: metformin + glimepiride + pioglitazone + albiglutide placebo<br>Metformin + glimepiride + pioglitazone + matching albiglutide placebo | Drug: placebo to match albiglutide<br>* albiglutide matching placebo weekly subcutaneous injection<br>Drug: metformin<br>* metformin<br>Drug: glimepiride<br>* glimepiride<br>Drug: pioglitazone<br>* pioglitazone<br>|
| Experimental: metformin + glimepiride + pioglitazone placebo + albiglutide<br>Metformin + open-label glimepiride + pioglitazone matching placebo + albiglutide | Biological: albiglutide<br>* albiglutide weekly subcutaneous injection<br>Drug: metformin<br>* metformin<br>Drug: glimepiride<br>* glimepiride<br>Drug: placebo to match pioglitazone<br>* pioglitazone matching placebo<br>|
| Active Comparator: met + glimepiride + pioglitazone placebo + albiglutide placebo<br>metformin + open-label glimepiride + pioglitazone placebo + albiglutide placebo | Drug: placebo to match albiglutide<br>* albiglutide matching placebo weekly subcutaneous injection<br>Drug: metformin<br>* metformin<br>Drug: glimepiride<br>* glimepiride<br>Drug: placebo to match pioglitazone<br>* pioglitazone matching placebo<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 | 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 value 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. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region. 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. Nine par. with post-BL values obtained >14 days after the last dose or after hyperglycemic rescue were included in the analysis population but were not analyzed for this endpoint. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 104 and Week 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. The 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, Week 104, and 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 FPG + Baseline HbA1c category + prior myocardial infarction history + age category + region. | Baseline and Week 52 | 
| Change From Baseline in FPG at Week 104 and Week 156 | 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. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline, Week 104, and Week 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) | 
| 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) was assessed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52. | 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) was 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 pre-rescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region. | Baseline and Week 52 | 
| Change From Baseline in Body Weight at Week 104 and 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. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline, Week 104, and Week 156 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes