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

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

The purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes who have never been treated with medication or have been taking medication for less than 24 weeks since their original diabetes diagnosis. The safety of this treatment will also be studied.

All eligible participants will receive single-blind placebo medication during the 2-week lead-in period. All participants may receive additional open-label treatment with metformin, 500-2000 mg, as needed for rescue, based on protocol specific criteria.

Key Inclusion Criteria

• Males and females, aged 18 to 77 years
• Type 2 diabetes with inadequate glycemic control, defined as: Group 1, hemoglobin A1c (HbA1c) ≥7% and ≤10%; Group 2, HbA1c ≥10.1% and ≤12.0%
• Drug naive, defined as never having received prescription medications for diabetes, having received prescription medications for diabetes for <24 weeks since the original diagnosis
• C-peptide ≥1.0 ng/mL at enrollment
• Body Mass Index ≤ 45.0 kg/m^2 at enrollment

Key Exclusion Criteria

• Urine albumin:creatinine ratio >1,800 mg/g
• Aspartate aminotransferase >3*upper limit of normal (ULN)
• Alanine aminotransferase >3*ULN
• Serum total bilirubin >2*ULN
• Serum creatinine ≥1.5 mg/dL for men; ≥1.4 mg/dLfor women
• Calcium value outside of the central laboratory normal reference range
• Positive hepatitis B surface antigen
• Positive anti-hepatitis C virus antibody
• Hemoglobin ≤11 g/dL for men; hemoglobin ≤10 g/dL for women
• Creatine kinase >3*ULN
• Abnormal free T4 values
• History of diabetes insipidus
• Symptoms of poorly controlled diabetes, including marked polyuria and polydipsia with greater than 10% weight loss in the 3 months prior to enrollment
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma
• Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
• Any of the following within 6 months of enrollment: Myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable congestive heart failure (CHF), CHF New York Heart Association Class III or IV status, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia
• History of unstable or rapidly progressing renal disease
• Conditions of congenital renal glucosuria
• Significant hepatic disease, including chronic active hepatitis and/or severe hepatic insufficiency
• Documented history of hepatotoxicity with any medication
• Documented history of severe hepatobiliary disease
• History of hemoglobinopathy, with the exception of sickle cell trait, thalassemia minor, or chronic or recurrent hemolysis
• Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks prior to enrollment
• Malignancy (with the exception of treated basal cell or treated squamous cell carcinoma) within 5 years of enrollment visit
• Known immunocompromised status, including individuals who had undergone organ transplantation or who had positive HIV results
• Administration of any antidiabetic therapy for more than 14 days (consecutive or not) during the 12 weeks prior to enrollment
• Administration of any antidiabetic therapy, other than any previously specified, at any dose, at any time during the 4 weeks prior to enrollment
• Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months prior to enrollment
• History of bariatric surgery or lap-band procedure
• Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of enrollment