A Study to Determine the Long Term Safety and Efficacy of Albiglutide in Combination With Oral Monotherapy Antihyperglycemic Medications in Japanese Patients With Type 2 Diabetes Mellitus

Phase 3

Completed

Conditions: Diabetes Mellitus

Interventions: Drug: Albiglutide
Drug: Sulfonylurea
Drug: Glinide
Drug: Alpha-glucosidase inhibitor
Drug: Thiazolidinedione
Drug: Biguanide

Registration Number: NCT01777282

Lead Sponsor: GlaxoSmithKline

Brief Summary: This study is designed to examine the long term safety and efficacy of weekly subcutaneously injected albiglutide in combination with a single oral antidiabetic drug for 52 weeks in Japanese subjects with type 2 diabetes mellitus.

Detailed Description: This study is designed to examine the long term safety and efficacy of weekly subcutaneously injected albiglutide in combination with a single oral antidiabetic drug for 52 weeks in Japanese subjects with type 2 diabetes mellitus. Subjects with a historical diagnosis of type 2 diabetes mellitus who are inadequately controlled on a single oral antidiabetic agent will be recruited into the study. Subjects will continue on their single antidiabetic agent and once weekly albiglutide will be added.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 374

Inclusion Criteria

Subjects with diagnosis of Type 2 Diabetes Mellitus, who are experiencing inadequate glycemic control and receiving treatment with a stable dose of a single oral antidiabetic medication
Body mass index (BMI) 17 to 40 kg/ m2 inclusive
Subjects with an HbA1c between 7.0% and 10.0% at Screening
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 GLP-1R agonist or DPP-IV inhibitor within 6 months before Screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Albiglutide + Sulfonylurea	Sulfonylurea	Albiglutide in combination with background sulfonylurea
Albiglutide + Glinide	Glinide	Albiglutide in combination with background glinide
Albiglutide + Alpha-glucosidase inhibitor	Alpha-glucosidase inhibitor	Albiglutide in combination with background alpha-glucosidase inhibitor
Albiglutide + Thiazolidinedione	Thiazolidinedione	Albiglutide in combination with background thiazolidinedione
Albiglutide + Sulfonylurea	Albiglutide	Albiglutide in combination with background sulfonylurea
Albiglutide + Biguanide	Albiglutide	Albiglutide in combination with background biguanide
Albiglutide + Thiazolidinedione	Albiglutide	Albiglutide in combination with background thiazolidinedione
Albiglutide + Glinide	Albiglutide	Albiglutide in combination with background glinide
Albiglutide + Alpha-glucosidase inhibitor	Albiglutide	Albiglutide in combination with background alpha-glucosidase inhibitor
Albiglutide + Biguanide	Biguanide	Albiglutide in combination with background biguanide

Primary Outcome Measures

Name	Time	Method
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)	From Baseline through Week 52	An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. Non-serious hypoglycemia events are not included.
Number of Participants With Any Hypoglycemic Event	From Baseline through Week 52	Hypoglycemia events are defined with respect to low plasma glucose level, mostly accompanied by typical symptoms and/or assistance needed from third party with glucose administration. These events were reported by the investigators upon verification of the plasma glucose levels, symptoms and assistance recorded by the participants, and/or plasma glucose values obtained from laboratory evaluations.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52	Baseline and 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 before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis.
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)	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 before the start of treatment. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	Baseline and Week 52	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 52 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline FPG observation carried forward for the analysis.
Change From Baseline in Body Weight at Week 52	Baseline and 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. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline weight observation carried forward for the analysis.
Time to Study Withdrawal Due to Hyperglycemia	Week 52	Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose \>=280 mg/dL (\>=15.5 mmol/L) from \>=Week 2 to \<Week 12 or \>=230 mg/dL (\>=12.8 mmol/L) from \>=Week 12 to \<Week 52.