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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 52-Week, Open-Label, Multicenter Study to Determine the Long Term Safety and Efficacy of Albiglutide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Japanese Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Albiglutide
* Drug: Sulfonylurea
* Drug: Biguanide
* Drug: Glinide
* Drug: Thiazolidinedione
* Drug: Alpha-glucosidase inhibitor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Active Comparator: Albiglutide + Sulfonylurea<br>Albiglutide in combination with background sulfonylurea | Drug: Albiglutide<br>* Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It is intended for single use by the subject. It is designed for manual reconstitution of the dose, priming, and insertion of the pen needle, and manual injection by the subject. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.<br>Drug: Sulfonylurea<br>* Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.<br>|
| Active Comparator: Albiglutide + Biguanide<br>Albiglutide in combination with background biguanide | Drug: Albiglutide<br>* Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It is intended for single use by the subject. It is designed for manual reconstitution of the dose, priming, and insertion of the pen needle, and manual injection by the subject. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.<br>Drug: Biguanide<br>* Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.<br>|
| Active Comparator: Albiglutide + Glinide<br>Albiglutide in combination with background glinide | Drug: Albiglutide<br>* Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It is intended for single use by the subject. It is designed for manual reconstitution of the dose, priming, and insertion of the pen needle, and manual injection by the subject. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.<br>Drug: Glinide<br>* Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.<br>|
| Active Comparator: Albiglutide + Thiazolidinedione<br>Albiglutide in combination with background thiazolidinedione | Drug: Albiglutide<br>* Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It is intended for single use by the subject. It is designed for manual reconstitution of the dose, priming, and insertion of the pen needle, and manual injection by the subject. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.<br>Drug: Thiazolidinedione<br>* Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.<br>|
| Active Comparator: Albiglutide + Alpha-glucosidase inhibitor<br>Albiglutide in combination with background alpha-glucosidase inhibitor | Drug: Albiglutide<br>* Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It is intended for single use by the subject. It is designed for manual reconstitution of the dose, priming, and insertion of the pen needle, and manual injection by the subject. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.<br>Drug: Alpha-glucosidase inhibitor<br>* Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) | 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. | From Baseline through Week 52 | 
| Number of Participants With Any Hypoglycemic Event | 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. | From Baseline through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline 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 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. | 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 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%. | Week 52 | 
| 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 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. | Baseline and Week 52 | 
| 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. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline weight observation carried forward for the analysis. | 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 >=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. | Week 52 | 

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