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

ClinicalTrials.gov processed this record on October 23, 2014