Clinical trial NCT01525212: Multiple Ascending Dose Study of BMS-929075 in Hepatitis C Virus (HCV) Infected Patients
Official title: Double-Blinded, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Antiviral Activity, Safety, Tolerability, and Pharmacokinetics of BMS-929075 in Treatment Naive Subjects Infected With Hepatitis C Virus Genotype 1
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Chronic Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-02-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: HCV RNA level on Day 4
timeFrame: Within 4 days after the first dose
Secondary outcomes:
measure: Maximum decrease from baseline in plasma HCV RNA levels during the period from Day 1 to Day 28
timeFrame: Days 1-28
measure: 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
timeFrame: Days 1-28
measure: 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
timeFrame: Days 1-28 (with SAE from screening to Day 30)
measure: Maximum observed plasma concentration (Cmax) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Minimum observed plasma concentration (Cmin) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Trough observed plasma concentration (Ctrough) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Time of maximum observed plasma concentration (Tmax) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Plasma half-life (T-HALF) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: Protein Binding (PB) of BMS-929075 derived from plasma concentration versus time
timeFrame: Day 3 (0h and 2h)
measure: Fraction of free drug in plasma (fu) of BMS-929075 derived from plasma concentration versus time
timeFrame: 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)
measure: The relationship between antiviral activity and measures of exposure to BMS-929075
timeFrame: Days 1-6
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: