Multiple Ascending Dose Study of BMS-929075 in Hepatitis C Virus (HCV) Infected Patients

• Maximum decrease from baseline in plasma HCV RNA levels during the period from Day 1 to Day 28 [ Time Frame: Days 1-28 ] [ Designated as safety issue: No ]
• Time course of the change from baseline in plasma HCV RNA levels and the time of maximum decrease during the period of Day 1 through Day 28 [ Time Frame: Days 1-28 ] [ Designated as safety issue: No ]
• Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests [ Time Frame: Days 1-28 (with SAE from screening to Day 30) ] [ Designated as safety issue: Yes ]
• Maximum observed plasma concentration (Cmax) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Minimum observed plasma concentration (Cmin) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Trough observed plasma concentration (Ctrough) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Time of maximum observed plasma concentration (Tmax) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Plasma half-life (T-HALF) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• Protein Binding (PB) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 3 (0h and 2h) ] [ Designated as safety issue: No ]
• Fraction of free drug in plasma (fu) of BMS-929075 derived from plasma concentration versus time [ Time Frame: Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h) ] [ Designated as safety issue: No ]
• The relationship between antiviral activity and measures of exposure to BMS-929075 [ Time Frame: Days 1-6 ] [ Designated as safety issue: No ]

The purpose of this study is to determine the change from baseline in HCV Ribonucleic acid (RNA) on Day 4 following three days of dosing with BMS-929075 in chronically genotype subtype 1a and 1b HCV infected subjects

• Drug: BMS-929075
  Oral Suspension, ≤ 25 mg, Once daily, 3 days
• Drug: BMS-929075
  Oral Suspension, ≤ 100 mg, Once daily, 3 days
• Drug: BMS-929075
  Oral Suspension, ≤ 400 mg, Once daily, 3 days
• Drug: BMS-929075
  Oral Suspension, (≤ 800 mg, Once daily) OR (≤ 400 mg, Twice daily), 3 days
• Drug: Placebo matching BMS-929075
  Oral Suspension, 0 mg, Once daily, 3 days
• Drug: Placebo matching BMS-929075
  Oral Suspension, 0 mg, (Once daily for ≤ 800 mg group) OR (Twice daily for ≤ 400 mg group), 3 days

• Experimental: Arm 1: BMS-929075 (≤ 25 mg) OR Placebo matching BMS-929075
  Interventions:

  • Drug: BMS-929075
  • Drug: Placebo matching BMS-929075
• Experimental: Arm 2: BMS-929075 (≤ 100 mg) OR Placebo matching BMS-929075
  Interventions:

  • Drug: BMS-929075
  • Drug: Placebo matching BMS-929075
• Experimental: Arm 3: BMS-929075 (≤ 400 mg) OR Placebo matching BMS-929075
  Interventions:

  • Drug: BMS-929075
  • Drug: Placebo matching BMS-929075
• Experimental: Arm 4: BMS-929075 (≤ 800 mg) OR Placebo matching BMS-929075
  Interventions:

  • Drug: BMS-929075
  • Drug: Placebo matching BMS-929075

Inclusion Criteria:

• Men and women, ages 18 to 65 years, inclusive
• Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy
• HCV genotype 1a or 1b only
• HCV RNA viral load of ≥ 100,000 IU/mL
• Have one of the following: i) Documented Fibrotest score of ≤ 0.72 and AST to platelet ratio index (APRI) ≤ 2; or ii) Documented liver biopsy within 12 months preceding Day 1 showing absence of cirrhosis
• Body Mass Index (BMI) of 18.0 to 35.0 kg/m2, inclusive

Exclusion Criteria:

• Any significant acute or chronic medical illness
• History of adrenal gland disease, including but not limited to adrenal insufficiency or Cushing's syndrome
• Current or recent (within 3 months of study drug administration) gastrointestinal disease
• Any major surgery within 4 weeks of study drug administration
• Any gastrointestinal surgery that could impact upon the absorption of study drug
• Positive for hepatitis B surface antigen (HBsAg)
• Positive for Human Immunodeficiency Virus (HIV) -1 and/or -2 antibodies
• Smoking > 10 cigarettes per day
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 5x upper limit of normal (ULN)
• Total Bilirubin ≥ 1.5x ULN
• Hemoglobin < 10 g/dL
• Platelets < 75,000 cell/μL
• ALC (absolute lymphocyte count) < 1000 cell/μL
• Creatinine clearance (as estimated by method of Cockcroft and Gault) less than 60 mL/min