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A Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01020565
First received: November 24, 2009
Last updated: August 4, 2010
Last verified: June 2010
History of Changes
  Purpose

The objectives of this study are to demonstrate that entecavir has antiviral activity with undetectable at Week 48, and to assess the safety and the pharmacokinetic in Japanese patients given entecavir at each dose of 0.1 and 0.5 mg for 52 weeks


Condition Intervention Phase
Chronic Hepatitis B
 Drug: Entecavir
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

Resource links provided by NLM:

Drug Information available for: Entecavir
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg [ Time Frame: Week 52 (end of dosing) plus 5 days ] [ Designated as safety issue: Yes ]
  • Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks [ Time Frame: Week 52 (end of dosing) plus 5 days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects HBeAg-positive at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, negative for HBeAg and normal serum ALT] at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects HBeAg-negative at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, remain negative for HBeAg and normal serum ALT] at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of subjects w/ histological improvement in liver (improvement in necroinflammatory score (≥2 points decrease, Knodell HAI3 score) & no worsening of fibrosis (≥1 point increase, Knodell fibrosis score) at Wk 48 liver biopsy compared to baseline [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
  • Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  • Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity [ Time Frame: Week 48, or at end of dosing (up to Week 52) ] [ Designated as safety issue: No ]
  • Incidence of resistance mutations of HBV isolates in subjects who have a rise in HBV DNA (by ≥1 log above the nadir for that subject) while on study drug. [ Time Frame: Week 48, or at end of dosing (up to Week 52) ] [ Designated as safety issue: No ]
  • Mutation of HBV DNA polymerase at Week 48 from baseline [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
  • Plasma concentrations of entecavir at selected time points during the treatment period [ Time Frame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36 ] [ Designated as safety issue: No ]
  • Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects [ Time Frame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: February 2003
Study Completion Date: February 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entecavir (0.1 mg) Drug: Entecavir
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks
Other Names:
  • Baraclude
  • BMS-200475
Experimental: Entecavir (0.5 mg) Drug: Entecavir
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks
Other Names:
  • Baraclude
  • BMS-200475

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documentation of chronic hepatitis B infection by ALL of the following:

    1. Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy
    2. Positive for HBeAg OR negative for HBeAg
    3. Documented HBV Viremia on 2 or more occasions and at screening visit: Viremia on sample drawn AND HBV DNA of ≥ 10*5* copies/mL by PCR assay at the screening visit
  • ALT in the range of 1.3 to 10 x ULN
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01020565

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

Publications:

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01020565     History of Changes
Other Study ID Numbers: AI463-053
Study First Received: November 24, 2009
Last Updated: August 4, 2010
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
 Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antiviral Agents
Entecavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013