A Phase III Study of BMS-512148 (Dapagliflozin) in Asian Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

Study Overview
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Brief Summary
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The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can improve (decrease) blood glucose values in Asian patients with Type 2 Diabetes who have never been treated with medication or have been on medication for less than 24 weeks since their original diagnosis of Diabetes. The safety of this treatment will also be studied.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Asian Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Dapagliflozin
* Drug: Metformin
* Drug: Dapagliflozin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 years old, with type 2 diabetes and with inadequate glycemic control Drug naive or treated with anti-diabetic medication for < 24 weeks C-peptide ≥ 1.0 ng/mL Body Mass Index ≤ 45.0 kg/m² Exclusion Criteria: AST and/or ALT > 3 times ULN Serum total bilirubin > 2 mg/dL Serum creatinine ≥ 1.50 mg/dL for men or ≥ 1.40 mg/dL for women Creatine kinase ≥ 3 times ULN Symptoms of severely uncontrolled diabetes Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 5 mg, Once daily, 24 weeks<br>* Other names: BMS-512148;Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks<br>* Other names: Glucophage®;Drug: Dapagliflozin Placebo<br>* Tablets, Oral, 0 mg, Once daily, 24 weeks<br>|
| Experimental: Group 2<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Once daily, 24 weeks<br>* Other names: BMS-512148;Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks<br>* Other names: Glucophage®;Drug: Dapagliflozin Placebo<br>* Tablets, Oral, 0 mg, Once daily, 24 weeks<br>|
| Experimental: Group 3<br> | Drug: Metformin<br>* Tablets, Oral, 500-2000 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks<br>* Other names: Glucophage®;Drug: Dapagliflozin Placebo<br>* Tablets, Oral, 0 mg, Once daily, 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period. | From Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double-blind period. | From Baseline to Week 24 | 
| Adjusted Mean Change From Baseline in 2-hour Post Liquid Meal Glucose (PLMG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Post Liquid Meal Glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PLMG measurements were obtained on Day 1 and week 24 in the double-blind period. | From Baseline to Week 24 | 
| Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period. | From Baseline to Week 24 | 
| Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants were estimated by modified logistic regression model. | From Baseline to Week 24 |