Chronic Hepatitis C
Conditions
Brief summary
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
Interventions
DRUGBMS-929075
Oral Suspension, ≤ 25 mg, Once daily, 3 days
DRUGPlacebo matching BMS-929075
Oral Suspension, 0 mg, Once daily, 3 days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HCV RNA level on Day 4 | Within 4 days after the first dose |
Secondary
| Measure | Time frame |
|---|---|
| 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 | Days 1-28 |
| 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 | Days 1-28 (with SAE from screening to Day 30) |
| Maximum observed plasma concentration (Cmax) of BMS-929075 derived from plasma concentration versus time | 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) |
| Minimum observed plasma concentration (Cmin) of BMS-929075 derived from plasma concentration versus time | 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) |
| Trough observed plasma concentration (Ctrough) of BMS-929075 derived from plasma concentration versus time | 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) |
| Maximum decrease from baseline in plasma HCV RNA levels during the period from Day 1 to Day 28 | Days 1-28 |
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-929075 derived from plasma concentration versus time | 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) |
| Plasma half-life (T-HALF) of BMS-929075 derived from plasma concentration versus time | 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) |
| Protein Binding (PB) of BMS-929075 derived from plasma concentration versus time | Day 3 (0h and 2h) |
| Fraction of free drug in plasma (fu) of BMS-929075 derived from plasma concentration versus time | 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) |
| The relationship between antiviral activity and measures of exposure to BMS-929075 | Days 1-6 |
| Time of maximum observed plasma concentration (Tmax) of BMS-929075 derived from plasma concentration versus time | 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) |
Countries
Australia
Outcome results
None listed