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

Study Overview
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Brief Summary
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A study to determine the safety and efficacy of albiglutide in subjects with type 2 diabetes.

Official Title
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A Randomized, Open-label, Parallel-group, Multicenter Study to Determine the Efficacy and Long-term Safety of Albiglutide Compared With Insulin 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: insulin glargine


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 within <6 weeks post-partum current symptomatic heart failure (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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: albiglutide weekly injection<br>albiglutide weekly subcutaneous injection | Biological: albiglutide<br>* albiglutide weekly injection<br>|
| Active Comparator: insulin glargine<br>insulin glargine daily injection | Drug: insulin glargine<br>* insulin glargine<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 + current antidiabetic therapy. Difference of least squares means (albiglutide - insulin glargine) 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 52 | 

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 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 + current antidiabetic therapy. | Baseline and Week 52 | 
| Change From Baseline in Fasting Plasma Glucose (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. | 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 achieved 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 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 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 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 + Baseline HbA1c category + 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 Glucose Profile Measured by 24-hour Area Under Curve (AUC) at Week 52 | A 24-hour glucose profile was collected at Baseline and Week 52 at a subset of sites in a subset of participants per treatment group using the continuous glucose monitoring device. Glucose measurements were obtained at 5 minute increments in the 24-hour period. The area under the curve (AUC) was determined using the trapezoidal method on the measurements obtained during the first 24 hours of continuous monitoring. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed. The Baseline value is the last non-missing value before the start of treatment. | Baseline and Week 52 | 
| Albiglutide Plasma Concentrations at Week 8 and Week 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 receiving albiglutide were initiated on a 30 mg weekly dosing regimen; however, beginning at Week 4, uptitration of albiglutide was allowed based on glycemic response. As such, albiglutide plasma concentrations achieved at each sampling time represent a mixed population of participants receiving either 30 mg or 50 mg weekly for various durations. | Weeks 8 and 24 | 

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