Multiple Ascending Dose Study of BMS-820132 in Patients With Type 2 Diabetes

• Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. [ Time Frame: Throughout the study drug administration period (14 days) ] [ Designated as safety issue: Yes ]
• Adverse events, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments. [ Time Frame: within 7 days after the final dose ] [ Designated as safety issue: Yes ]

• Maximum observed plasma concentration (Cmax) of BMS-820132 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
• Time of maximum observed plasma concentration (Tmax) of BMS-820132 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
• Trough observed plasma concentration (Cmin) of BMS-820132 [ Time Frame: Day 1 through Day 14 (selected days) ] [ Designated as safety issue: No ]
• Area under the plasma concentration-time curve over one dosing interval [AUC(TAU)] of BMS-820132 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
• Accumulation index (AI) of BMS-820132 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
• Half life (T-Half) of BMS-820132 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
• AUC(0-24 h) and postprandial AUC(0-4h) for biomarkers of glucose homeostasis [ Time Frame: Day -1, Day 1, Day 7 and Day 14 ] [ Designated as safety issue: No ]

• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 1 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days -1 ] [ Designated as safety issue: No ]
• Excretion of the investigational drug and metabolites from the body. [ Time Frame: Days 1 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 2 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 4 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 6 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 8 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 10 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 12 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 14 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 15 ] [ Designated as safety issue: No ]
• Exposure to the investigational drug and its metabolites. [ Time Frame: Days 16 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days 1 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days 2 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days 14 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days 7 ] [ Designated as safety issue: No ]
• Pharmacodynamic activity of the investigational drug on biomarkers. [ Time Frame: Days 15 ] [ Designated as safety issue: No ]
• Excretion of the investigational drug and metabolites from the body. [ Time Frame: Days 2 ] [ Designated as safety issue: No ]
• Excretion of the investigational drug and metabolites from the body. [ Time Frame: Days 14 ] [ Designated as safety issue: No ]
• Excretion of the investigational drug and metabolites from the body. [ Time Frame: Days 15 ] [ Designated as safety issue: No ]

BMS-820132 is an investigational new drug being developed by BMS for treating Type 2 diabetes. The purpose of this study is to test the safety/tolerability (potential side effects) of multiple doses of the investigational new drug, as well as the amount of study drug in the blood and its effects on blood sugar,in subjects with type 2 diabetes.

Study Classification: Safety, Pharmacokinetics/dynamics

• Drug: Placebo
  capsule, Oral, 0.0mg, twice daily, 14 day
• Drug: Placebo
  Capsule, Oral, 0.0mg, once daily, 14 day
• Drug: BMS-820132
  Capsule, Oral, 15mg, twice daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, Oral, 60mg, twice daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, oral, 150mg, twice daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, Oral, 300mg, twice daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, Oral, 450mg, twice daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, Oral, To be determined (TBD), once daily, 14 day
  Other Name: BMS-820132
• Drug: BMS-820132
  Capsule, Oral, 5 mg, twice daily, 14 day

• Active Comparator: Arm 1 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 2 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 3 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 4 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 5 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 6 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 7 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 8 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132
• Active Comparator: Arm 9 BMS-820132 or placebo
  Interventions:

  • Drug: Placebo
  • Drug: BMS-820132

Inclusion Criteria:

• Males and females of childbearing potential (willing to use an acceptable method of contraception), or females of non-childbearing potential (i.e., post-menopausal or surgically sterile).
• Diagnosis of type 2 diabetes treated with metformin monotherapy (at least 1500 mg/day for at least 6 months) on a stable regimen for at least 2 months.
• Body Mass Index (BMI) of 18.5 to 40 kg/m2.
• Fasting glucose in the range of 125-275 mg/dL.
• Hemoglobin A1c (HbA1c) in the range of 7.0% -11.0%.
• Fasting C-peptide > 1 ng/mL.

Exclusion Criteria:

• Clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations, and any significant acute or chronic medical illness other than stable and well controlled hypertension, microalbuminuria, dyslipidemia, depression, or hypothyroidism.
• History of diabetic ketoacidosis, hyperosmolar nonketotic syndrome, lactic acidosis, hypoglycemia (i.e., ≥ 1 self-reported episodes of hypoglycemia within the last 3 months or ≥ 2 self-reported episodes of hypoglycemia within the last 6 months), or hypoglycemia unawareness.
• Any major surgery within 4 weeks of study drug administration.
• Any gastrointestinal surgery that could impact upon the absorption of study drug.
• Smoking more than 10 cigarettes per day.
• Recent drug or alcohol abuse.
• Women who are pregnant or breastfeeding.
• Positive urine screen for drugs of abuse.
• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV)-1, -2 antibody.