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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01525212
First received: January 31, 2012
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis C
Drug: BMS-929075
Drug: Placebo matching BMS-929075
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • HCV RNA level on Day 4 [ Time Frame: Within 4 days after the first dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 0
Study Start Date: April 2012
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: BMS-929075 (≤ 25 mg) OR Placebo matching BMS-929075 Drug: BMS-929075
Oral Suspension, ≤ 25 mg, Once daily, 3 days
Drug: Placebo matching BMS-929075
Oral Suspension, 0 mg, Once daily, 3 days
Experimental: Arm 2: BMS-929075 (≤ 100 mg) OR Placebo matching BMS-929075 Drug: BMS-929075
Oral Suspension, ≤ 100 mg, Once daily, 3 days
Drug: Placebo matching BMS-929075
Oral Suspension, 0 mg, Once daily, 3 days
Experimental: Arm 3: BMS-929075 (≤ 400 mg) OR Placebo matching BMS-929075 Drug: BMS-929075
Oral Suspension, ≤ 400 mg, Once daily, 3 days
Drug: Placebo matching BMS-929075
Oral Suspension, 0 mg, Once daily, 3 days
Experimental: Arm 4: BMS-929075 (≤ 800 mg) OR Placebo matching BMS-929075 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 for ≤ 800 mg group) OR (Twice daily for ≤ 400 mg group), 3 days

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525212

Locations
Australia, Queensland
Local Institution
Herston, Queensland, Australia, 4006
Australia, South Australia
Local Institution
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Local Institution
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01525212     History of Changes
Other Study ID Numbers: AI457-002
Study First Received: January 31, 2012
Last Updated: June 19, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on September 18, 2014