Randomized, Placebo-Controlled, Double-Blind, Ascending Single and Multiple Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-963272 in Healthy Subjects

Randomized, Placebo-Controlled, Double-Blind, Ascending Single and Multiple Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-963272 in Healthy Subjects

The purpose of this study is to evaluate the safety profile, tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) following single and multiple oral doses of BMS-963272 in healthy subjects.

Study Classification: Safety, PK/PD

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs and clinical laboratory determinations
• Body Mass Index (BMI) of 27 to 40 kg/m2 inclusive. BMI = weight (kg)/ [height (m)]2
• Females (not of childbearing potential and males, ages 18 to 55 years, inclusive. Female subjects must have documented proof that they are not of childbearing potential
• Azoospermic males and women who are not of child-bearing potential (i.e. are postmenopausal or surgically sterile; see section 3.3.3 for the definition of WOCBP) are exempt from contraceptive requirements. However, women must still undergo pregnancy testing as described in this section

Exclusion Criteria:

• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population

• Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat.

  i)PR ≥ 210 msec ii)QRS ≥ 120 msec iii)QT ≥ 500 msec iv)QTcF ≥ 450 msec

• Positive urine screen for drugs of abuse

• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody

• Moderate anemia (hemoglobin < 11 g/dL for men and < 10 g/dL for women)

• aspartate aminotransferase (AST) > 1.3x ULN

• alanine aminotransferase (ALT) > 1.3x ULN

• Total bilirubin > 1.3x upper limit of normal (ULN)

• estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2 (calculated using CKD-EPI formula)

• HbA1c > 6.5%

• Fasting total cholesterol > 300 mg/dl

• Fasting triglycerides > 400 mg/dl

• Systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 95 mm Hg, confirmed by repeat measurement

• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

• History of lactose intolerance