Study in Japan of the Safety And Antiviral Activity in Adults With Chronic Hepatitis B Current Lamivudine Therapy

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01037166
First received: December 17, 2009
Last updated: January 24, 2011
Last verified: June 2010
  Purpose

The objectives are to demonstrate that entecavir has antiviral activity undetectable HBV DNA measured, the Roche AmplicorTM PCR at Week 48, and to assess the safety and the pharmacokinetic of entecavir in Japanese patients with hepatitis B who have an incomplete response to current lamivudine therapy


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 With Incomplete Response to Current Lamivudine Therapy

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • To assess the safety (the incidence of clinical adverse events and discontinuations due to adverse events) [ Time Frame: Week 52 (end of dosing) plus 5 days ] [ Designated as safety issue: Yes ]
  • To assess the proportion of subjects with reduction in HBV DNA by ≥ 2 log10 or to undetectable level (< 400 copies/mL) [ Time Frame: at Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change from baseline in the log*10* 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 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 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 ]

Enrollment: 84
Study Start Date: December 2002
Study Completion Date: February 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entecavir (0.5 mg) Drug: Entecavir
Tablet, P.O., 0.5 mg or 1mg, once daily, 52 weeks
Other Names:
  • Baraclude
  • BMS-200475
Experimental: Entecavir (1mg) Drug: Entecavir
Tablet, P.O., 0.5 mg or 1mg, 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. Patient who have received lamivudine therapy for 24 weeks or more, or patient who have documented YMDD mutation or other lamivudine-resistant mutation while on lamivudine
    3. Documented HBV Viremia ≥ 10*5: copies/mL
  • ALT in the range of 1.3 to 10 x ULN
  • Subjects must have well-compensated liver disease a) value

Exclusion Criteria:

-

  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: NCT01037166

Locations
Japan
Local Institution
Aichi-Gun, Aichi, Japan, 480-1195
Local Institution
Nagoya, Aichi, Japan, 466-8550
Local Institution
Nagoya-Shi, Aichi, Japan, 467-8602
Local Institution
Chiba-Shi, Chiba, Japan
Local Institution
Kurume, Fukuoka, Japan
Local Institution
Ogaki-Shi, Gifu, Japan, 503-8502
Local Institution
Asahikawa-Shi, Hokkaido, Japan, 070-0054
Local Institution
Sapporo-Shi, Hokkaido, Japan, 060-0033
Local Institution
Akashi-Shi, Hyogo, Japan, 673-0848
Local Institution
Morioka-Shi, Iwate, Japan, 020-8505
Local Institution
Sendai, Miyagi, Japan
Local Institution
Okayama-Shi, Okayama, Japan, 700-0082
Local Institution
Minato-Ku, Tokyo, Japan, 105-0001
Local Institution
Musashino-Shi, Tokyo, Japan, 180-0023
Local Institution
Shinjuku-Ku, Tokyo, Japan, 162-8666
Local Institution
Kyoto, Japan
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01037166     History of Changes
Other Study ID Numbers: AI463-052
Study First Received: December 17, 2009
Last Updated: January 24, 2011
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
Lamivudine
Entecavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 31, 2014