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

This study is not yet open for participant recruitment.
Verified January 2012 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01525212
First received: January 31, 2012
Last updated: April 30, 2012
Last verified: January 2012
History of Changes
  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:

U.S. FDA Resources

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 ]

Estimated Enrollment: 40
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01525212

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
Australia, Queensland
Local Institution Not yet recruiting
Herston, Queensland, Australia, 4006
Contact: Site 003            
Australia, South Australia
Local Institution Not yet recruiting
Adelaide, South Australia, Australia, 5000
Contact: Site 002            
Australia, Victoria
Local Institution Not yet recruiting
Melbourne, Victoria, Australia, 3004
Contact: Site 004            
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

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: April 30, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
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 May 19, 2013