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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01733758
• Other study ID #: 113121
• Status: Completed
• Phase: Phase 3
• First received: November 21, 2012
• Last updated: December 10, 2015
• Start date: February 2013
• Est. completion date: February 2015

Study information

• Verified date: October 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 494
• Est. completion date: February 2015
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Albiglutide 30 mg weekly
Albiglutide will be available as a pen injector that delivers 30mg of albiglutide
• Albiglutide 50 mg weekly
Albiglutide will be available as a pen injector that delivers 50mg of albiglutide
• Placebo
Albiglutide matching placebo will be available as a pen injector
• Liraglutide 0.9 mg daily
Liraglutide will be available as prefilled multidose pens that can deliver 0.9 mg dose

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Fukushima
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kochi
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nara
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Okinawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tochigi
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Yamaguchi

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Baseline through Week 52	No
Secondary	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	No