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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020565
• Other study ID #: AI463-053
• Status: Completed
• Phase: Phase 2
• First received: November 24, 2009
• Last updated: August 4, 2010
• Start date: February 2003
• Est. completion date: February 2005

Study information

• Verified date: June 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2005
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Entecavir
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

References & Publications (1)

Kobashi H, Takaguchi K, Ikeda H, Yokosuka O, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Sakaguchi K, Shiratori Y. Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan. J Gastroenterol Hepatol. 2009 Feb;24(2):255-61. doi: 10.1111/j.1440-1746.2008.05593.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg		Week 52 (end of dosing) plus 5 days	Yes
Primary	Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks		Week 52 (end of dosing) plus 5 days	Yes
Primary	Proportion of subjects with reduction in HBV DNA by =2 log10 or to undetectable level (<400 copies/mL) by PCR assay		Week 48	No
Secondary	Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48		Baseline, Week 48	No
Secondary	Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48		Week 48	No
Secondary	Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48		Week 48	No
Secondary	Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48		Week 48	No
Secondary	Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48		Week 48	No
Secondary	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		Week 48	No
Secondary	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		Week 48	No
Secondary	Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug		Week 72	No
Secondary	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		Baseline, Week 48	No
Secondary	Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis		Week 52	No
Secondary	Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity		Week 48, or at end of dosing (up to Week 52)	No
Secondary	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.		Week 48, or at end of dosing (up to Week 52)	No
Secondary	Mutation of HBV DNA polymerase at Week 48 from baseline		Baseline, Week 48	No
Secondary	Plasma concentrations of entecavir at selected time points during the treatment period		pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36	No
Secondary	Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects		pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36	No

External Links

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