Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes

• Mean change from baseline in Glycosylated hemoglobin (HbA1c) [ Time Frame: Baseline (Day 1) ] [ Designated as safety issue: No ]
• Mean change from baseline in Glycosylated hemoglobin (HbA1c) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

• Mean change from baseline in fasting plasma glucose (FPG) [ Time Frame: Baseline (Day 1) and Week 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in 2-hour post-prandial glucose during a liquid meal tolerance test (2-h MTT) [ Time Frame: Baseline (Day 1) and Week 24 ] [ Designated as safety issue: No ]
• Mean change from baseline in total body weight [ Time Frame: Baseline (Day 1) and Week 24 ] [ Designated as safety issue: No ]
• Percent of subjects achieving a therapeutic glycemic response, defined as a HbA1c < 7.0% [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

The purpose of this study is to learn if BMS-512148 (Dapagliflozin) as part of a triple combination therapy can improve (decrease) hemoglobin A1c in patients with type 2 diabetes after 24 weeks of treatment compared to a 2 drug oral antidiabetic therapy. The safety of this treatment will also be studied.

Prior to randomization, all eligible subjects will receive open-label treatment with Saxagliptin 5mg and Metformin IR during the 16-week open-label treatment period.

• Drug: Dapagliflozin
  Tablets, Oral, 10 mg, Once daily, Up to 52 weeks
• Drug: Placebo matching with Dapagliflozin
  Tablets, Oral, 0 mg, Once daily, Up to 52 weeks
• Drug: Saxagliptin
  Tablets, Oral, 5 mg, Once daily, Up to 52 weeks
  Other Name: Onglyza
• Drug: Metformin immediate release (IR)
  Tablets, Oral, ≥ 1500 mg, Twice daily, Up to 52 weeks

• Experimental: Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR
  Interventions:

  • Drug: Dapagliflozin
  • Drug: Saxagliptin
  • Drug: Metformin immediate release (IR)
• Experimental: Arm 2: Placebo + Saxagliptin + Metformin IR
  Interventions:

  • Drug: Placebo matching with Dapagliflozin
  • Drug: Saxagliptin
  • Drug: Metformin immediate release (IR)

Inclusion Criteria:

• Males and females, ≥ 18 years old, with type 2 diabetes with inadequate glycemic control HbA1c ≥ 7.5% - ≤ 11.5%
• Stable dose of Metformin for at least 8 weeks
• C-peptide ≥ 1.0 ng/mL
• Body Mass Index ≤ 45.0 kg/m2

Exclusion Criteria:

• Estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73m2 or serum creatinine (Scr) ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females
• Aspartate aminotransferase (AST) and /or Alanine aminotransferase (ALT) > 3.0 times the upper limit of normal (ULN)
• Serum total bilirubin > 2.5 x ULN
• Systolic blood pressure (SBP) ≥ 160 mmHg and/or Diastolic blood pressure (DBP) ≥ 100mmHg
• Cardiovascular disease within 3 months of the screening visit
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases