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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: BMS-929075; Drug: BMS-929075; Drug: BMS-929075; Drug: BMS-929075; Drug: Placebo matching BMS-929075; Drug: Placebo matching BMS-929075

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: BMS-929075 (≤ 25 mg) OR Placebo matching BMS-929075	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 2: BMS-929075 (≤ 100 mg) OR Placebo matching BMS-929075	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 3: BMS-929075 (≤ 400 mg) OR Placebo matching BMS-929075	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 4: BMS-929075 (≤ 800 mg) OR Placebo matching BMS-929075	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HCV RNA level on Day 4	Within 4 days after the first dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum decrease from baseline in plasma HCV RNA levels during the period from Day 1 to Day 28	Days 1-28
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)
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)
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): February 1, 2013
• Study Completion (Anticipated): February 1, 2013

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: January 31, 2012
• First Posted (Estimate): February 2, 2012

Study Record Updates

• Last Update Posted (Estimate): June 21, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: AI457-002