A Monotherapy Study to Evaluate the Efficacy and Safety of 2 Dose Levels of Albiglutide in Japanese Subjects With Type 2 Diabetes Mellitus (T2DM)

Study Overview
=================
Brief Summary
-----------------
This study is designed to examine the efficacy and safety of 2 dose levels of weekly subcutaneously injected albiglutide compared with placebo and an open label reference arm of daily subcutaneous injections of liraglutide, in Japanese subjects with Type 2 diabetes mellitus.

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

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Albiglutide 30 mg weekly
* Drug: Albiglutide 50 mg weekly
* Drug: Placebo
* Drug: Liraglutide 0.9 mg daily


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with diagnosis of Type 2 Diabetes Mellitus, treated with diet and exercise or a stable dose of 1 OAD at screening Body mass index (BMI) 17 to 40 kg/ m^2 inclusive Subjects who are OAD naïve, HbA1c between 7.0% and 10.0% at Screening and at Visit 2; for subjects who enter the study with 1 OAD, HbA1c between 6.5% and 9.5% at Screening and HbA1c between 7.0% and 10.0% at Visit 2 Creatinine clearance >30 mL/min (calculated using the Cockcroft-Gault formula) Exclusion Criteria: History of type 1 diabetes mellitus •Female subject is pregnant, lactating, or <6 weeks postpartum• Clinically significant cardiovascular and/or cerebrovascular disease Current ongoing symptomatic biliary disease, clinical signs or symptoms of pancreatitis, or a history of chronic or acute pancreatitis, as determined by the investigator Serum amylase >=3 ×ULN and/or serum lipase >=2 × ULN and/or subject is experiencing any symptoms possibly related to pancreatitis Prior use of a TZD or GLP-1R agonist within 4 months before Screening

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albiglutide 30 mg weekly<br>Subjects will be randomly assigned to double blind albiglutide 30 mg weekly treatment for 52 weeks | Drug: Albiglutide 30 mg weekly<br>* Albiglutide will be available as a pen injector that delivers 30mg of albiglutide<br>Drug: Placebo<br>* Albiglutide matching placebo will be available as a pen injector<br>|
| Experimental: Albiglutide 50 mg weekly<br>Subjects will be randomly assigned to double blind albiglutide 50 mg weekly until Week 52 | Drug: Albiglutide 50 mg weekly<br>* Albiglutide will be available as a pen injector that delivers 50mg of albiglutide<br>|
| Placebo Comparator: Placebo<br>Subjects will be randomly assigned to double blind matching albiglutide placebo administered weekly. Subjects will then cross-over to double-blind treatment with albiglutide 30 mg weekly at Week 24 until Week 52 | Drug: Placebo<br>* Albiglutide matching placebo will be available as a pen injector<br>|
| Active Comparator: Liraglutide 0.9 mg daily<br>Subjects will be randomly assigned to open-label liraglutide for 52 weeks | Drug: Liraglutide 0.9 mg daily<br>* Liraglutide will be available as prefilled multidose pens that can deliver 0.9 mg dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | 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 nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Based on analysis of covariance (ANCOVA): Change at Week 24 = treatment (placebo, albiglutide 30 mg, albiglutide 50 mg) + Baseline HbA1c + prior diabetes therapy + age category (<65 years versus ≥65 years). Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c carried forward for the analysis unless the value is past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group and not included in the primary endpoint analysis model. Descriptive summary statistics are provided as a separate outcome measure. | Baseline and Week 24 | 
| Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | 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 nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c value carried forward for the summary, unless the value was past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group; descriptive statistics comparing albiglutide and liraglutide were exploratory endpoints. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 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 Baseline HbA1c value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. | Baseline and Week 52 | 
| Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as <6.5% and <7.0%. Participants who discontinued the study before Week 24 had their last post-Baseline HbA1c value carried forwrad for the summary unless the value was past 14 days after the last dose of study drug. | Week 24 | 
| Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) 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. Clinically meaningful levels of response in HbA1c are defined as <6.5% and <7.0%. | Week 52 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 24 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline FPG observation carried forward for the summary unless the value was 14 days past the last dose of study drug. | Baseline and Week 24 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline. | Baseline and Week 52 | 
| Change From Baseline in Body Weight at Week 24 | The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 24 minus the value at Baseline. Participants who discontinued from the study treatment before Week 24 had their last non-missing weight carried forward for the summary, unless the value is past 14 days after the last dose of study drug. | Baseline and Week 24 | 
| Change From Baseline in Body Weight at Week 52 | The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline. | Baseline and Week 52 | 
| Time to Study Withdrawal Due to Hyperglycemia | Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose (FPG) ≥280 mg/dL (≥15.5 mmol/L) from ≥Week 2 to <Week 4, ≥250 mg/dL (≥13.9 mmol/L) from ≥Week 4 to <Week 12, or ≥230 mg/dL (≥12.8 mmol/L) from ≥Week 12 to <Week 52, confirmed a second evaluation within 7 days. | Baseline through Week 52 | 
| Time to Study Withdrawal for Any Reason | Time to withdrawal was calculated as the number of days between the date of first dose and the date of withdrawal plus 1. Time to withdrawal was summarized by visit. | Baseline through Week 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
albiglutide, Japanese, GSK716155, Type 2 diabetes mellitus, glucagon-like peptide 1