A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Dapagliflozin placebo; Metformin
Intervention description: Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks
Intervention MeSH terms: Metformin; Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1067.0
Sex: All
Minimum age: 18 Years
Maximum age: 77 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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