An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01037062
First received: December 17, 2009
Last updated: January 24, 2011
Last verified: December 2009
  Purpose

To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy


Condition Intervention Phase
Chronic Hepatitis B
Drug: Entecavir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Rollover Study of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection Who Have Completed Previous Phase II Studies in Japan But Who Require Further Treatment

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • To provide open-label entecavir to subjects who have completed previous blinded entecavir trials in Japan and are assessed by the investigator as likely to benefit from additional anti-hepatitis B therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of clinical adverse events and discontinuations due to adverse events of entecavir for each cohort [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing ] [ Designated as safety issue: Yes ]
  • Incidence of laboratory abnormalities of of entecavir for each cohort [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 post dosing ] [ Designated as safety issue: Yes ]
  • Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum [ Time Frame: Day 1, Week 12, Week 24 and every subsequent 24 week during dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) [ Time Frame: Day 1, Week 12, Week 24 and every subsequent 24 week during dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT at Week 48 [ Time Frame: Day 1, Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve HBV DNA levels by PCR assay less than the limit of quantification (LOQ) [ Time Frame: Day 1, Week 12, 24, and subsequent 24 week during dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects positive for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ, normal serum ALT, and seroconversion [ Time Frame: Week 8, 16, 24 post dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects negative for HBeAg at baseline who achieve HBV DNA levels by PCR assay less than LOQ and normal ALT and remain negative for HBeAg [ Time Frame: Day 1, Week 12, Week 24 and every subsequent 24 weeks during dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieved Complete Response during therapy, who have sustained Complete Response for 24 weeks after stopping drug [ Time Frame: 24 Week post dosing ] [ Designated as safety issue: No ]
  • Proportion of subjects with histological improvement in the liver at Wks 48 & 96 [improvement in necroinflammatory score and no worsening of fibrosis at Wks 48 & 96 liver biopsy compared to baseline & to baseline in previous study] [ Time Frame: Week 48, 96 ] [ Designated as safety issue: No ]
  • NChanges in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis [ Time Frame: Week 48 & Week 96 ] [ Designated as safety issue: No ]
  • Incidence of genotypic changes in HBV DNA polymerase conferring resistance to entecavir in subjects with confirmed ≥1 log10 increase in HBV DNA from nadir on treatment [ Time Frame: Week 2, 4, ± days, Week 8 every 4 weeks ± 7 days ] [ Designated as safety issue: No ]

Enrollment: 282
Study Start Date: December 2003
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entecavir Drug: Entecavir
Tablet, P.O. 0.5, 1 mg, once daily
Other Names:
  • Baraclude
  • BMS-200475

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who completed a previous entecavir Phase II studies (AI463047, 052 or 053);
  • ALT ≤ 10 x upper limit of normal;
  • Subjects must have well-compensated liver disease according to ALL of the following criteria;

    1. Prothrombin time ≤ 3 seconds prolonged compared to control value or INR ≤ 1.5
    2. Serum albumin ≥ 3 g/dL (≥ 30 g/L)
    3. Serum bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L)

Exclusion Criteria:

  • Sex and Reproductive Status Exceptions
  • Target Disease Exceptions
  • Medical History and Concurrent Diseases
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01037062

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
Nagoya-Shi, Aichi, Japan, 457-0866
Local Institution
Chiba-Shi, Chiba, Japan
Local Institution
Onsen-Gun, Ehime, Japan, 791-0204
Local Institution
Fukuoka-Shi, Fukuoka, Japan, 814-0180
Local Institution
Kurume, Fukuoka, Japan
Local Institution
Gifu-Shi, Gifu, Japan, 500-8513
Local Institution
Ogaki-Shi, Gifu, Japan, 503-8502
Local Institution
Fukuyama-Shi, Hiroshima, Japan, 721-0971
Local Institution
Hiroshima City, Hiroshima, Japan, 734-0037
Local Institution
Hiroshima-Shi, Hiroshima, Japan, 730-8518
Local Institution
Asahikawa-Shi, Hokkaido, Japan, 070-0054
Local Institution
Sapporo-Shi, Hokkaido, Japan, 006-0813
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
Mitoyo-Gun, Kagawa, Japan, 769-1601
Local Institution
Takamatsu-City, Kagawa, Japan
Local Institution
Kumamoto-Shi, Kumamoto, Japan, 860-8556
Local Institution
Sendai, Miyagi, Japan
Local Institution
Miyazaki-Gun, Miyazaki, Japan, 889-1692
Local Institution
Matsumoto City, Nagano, Japan, 390-0802
Local Institution
Nagasaki City, Nagasaki, Japan
Local Institution
Omura-Shi, Nagasaki, Japan, 856-0000
Local Institution
Oita-Gun, Oita, Japan, 879-5503
Local Institution
Kurashiki-Shi, Okayama, Japan, 710-8602
Local Institution
Okayama-Shi, Okayama, Japan, 700-8505
Local Institution
Okayama-Shi, Okayama, Japan, 700-0082
Local Institution
Okayama-Shi, Okayama, Japan, 700-8511
Local Institution
Tsuyama-Shi, Okayama, Japan, 708-0841
Local Institution
Kawachinagano-Shi, Osaka, Japan, 86-0008
Local Institution
Osaka-Shi, Osaka, Japan, 553-0003
Local Institution
Sakai-Shi, Osaka, Japan, 591-8025
Local Institution
Suita-Shi, Osaka, Japan
Local Institution
Iruma-Gun, Saitama, Japan, 350-0495
Local Institution
Minato-Ku, Tokyo, Japan, 105-0001
Local Institution
Musashino-Shi, Tokyo, Japan, 180-0023
Local Institution
Shinjuku-Ku, Tokyo, Japan, 160-8582
Local Institution
Shinjuku-Ku, Tokyo, Japan, 162-8655
Local Institution
Shinjuku-Ku, Tokyo, Japan, 162-8666
Local Institution
Ube-Shi, Yamaguchi, Japan, 755-0067
Local Institution
Nakakoma-Gun, Yamanashi, Japan, 409-3821
Local Institution
Kyoto, Japan
Local Institution
Niigata, Japan
Local Institution
Osaka, Japan
Local Institution
Tokyo, Japan, 173-8610
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: NCT01037062     History of Changes
Other Study ID Numbers: AI463-060
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
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014