Efficacy and Safety of Albiglutide in Treatment of Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine if albiglutide is safe and effective in the treatment of 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 When Used in Combination With Metformin Compared With Metformin Plus Sitagliptin, Metformin Plus Glimepiride, and Metformin Plus 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
* Drug: sitagliptin
* Drug: glimepiride
* Drug: metformin
* Biological: placebo albiglutide
* Drug: placebo sitagliptin
* Drug: placebo glimepiride


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 current symptomatic heart failure (NYHA Class III or 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 + metformin<br>Albiglutide + metformin + placebo sitagliptin + placebo glimepiride | Biological: albiglutide<br>* albiglutide<br>Drug: metformin<br>* Metformin<br>Drug: placebo sitagliptin<br>* placebo to match sitagliptin<br>Drug: placebo glimepiride<br>* placebo to match glimepiride<br>|
| Active Comparator: sitagliptin + metformin<br>Sitagliptin + metformin + placebo albiglutide + placebo glimepiride | Drug: sitagliptin<br>* sitagliptin<br>Drug: metformin<br>* Metformin<br>Biological: placebo albiglutide<br>* placebo to match albiglutide<br>Drug: placebo glimepiride<br>* placebo to match glimepiride<br>|
| Active Comparator: glimepiride + metformin<br>Glimepiride + metformin + placebo albiglutide + placebo sitagliptin | Drug: glimepiride<br>* Glimepiride<br>Drug: metformin<br>* Metformin<br>Biological: placebo albiglutide<br>* placebo to match albiglutide<br>Drug: placebo sitagliptin<br>* placebo to match sitagliptin<br>|
| Active Comparator: metformin + placebo<br>Metformin + placebo albiglutide + placebo sitagliptin + placebo glimepiride | Drug: metformin<br>* Metformin<br>Biological: placebo albiglutide<br>* placebo to match albiglutide<br>Drug: placebo sitagliptin<br>* placebo to match sitagliptin<br>Drug: placebo glimepiride<br>* placebo to match glimepiride<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 104 | 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 104 minus the value at BL. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region. Difference of least squares means (albiglutide - placebo, albiglutide - sitagliptin, albiglutide - glimepiride) is from the ANCOVA model. The last observation carried forward (LOCF) method was used to impute missing post-Baseline 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 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at 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. 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 Week 156 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 104 | 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 104 | 
| Change From Baseline in FPG at 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 and Week 156 | 
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 104 | The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 52) were assessed. | Week 104 | 
| 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 achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 156) were assessed. | Week 156 | 
| Time to Hyperglycemia Rescue | Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue.The conditions for hyperglycemic 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 week | From the start of study medication until the end of the treatment (up to Week 156) | 
| Change From Baseline in Body Weight at Week 104 | 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 + Baseline HbA1c category + prior myocardial infarction history + age category + region. | Baseline and Week 104 | 
| 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. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. | Baseline and Week 156 | 

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