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

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 With Incomplete Response to Current Lamivudine Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01037166
• Other study ID #: AI463-052
• Status: Completed
• Phase: Phase 2
• First received: December 17, 2009
• Last updated: January 24, 2011
• Start date: December 2002
• 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 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• 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. 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:

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., 0.5 mg or 1mg, once daily, 52 weeks

Locations

Country	Name	City	State
Japan	Local Institution	Aichi-Gun	Aichi
Japan	Local Institution	Akashi-Shi	Hyogo
Japan	Local Institution	Asahikawa-Shi	Hokkaido
Japan	Local Institution	Chiba-Shi	Chiba
Japan	Local Institution	Kurume	Fukuoka
Japan	Local Institution	Kyoto
Japan	Local Institution	Minato-Ku	Tokyo
Japan	Local Institution	Morioka-Shi	Iwate
Japan	Local Institution	Musashino-Shi	Tokyo
Japan	Local Institution	Nagoya	Aichi
Japan	Local Institution	Nagoya-Shi	Aichi
Japan	Local Institution	Ogaki-Shi	Gifu
Japan	Local Institution	Okayama-Shi	Okayama
Japan	Local Institution	Sapporo-Shi	Hokkaido
Japan	Local Institution	Sendai	Miyagi
Japan	Local Institution	Shinjuku-Ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Suzuki F, Toyoda J, Katano Y, Sata M, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Kumada H. Efficacy and safety of entecavir in lamivudine-refractory patients with chronic hepatitis B: randomized controlled trial in Japanese patients. J Gastroenterol Hepatol. 2008 Sep;23(9):1320-6. doi: 10.1111/j.1440-1746.2008.05455.x. Epub 2008 Jun 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the safety (the incidence of clinical adverse events and discontinuations due to adverse events)		Week 52 (end of dosing) plus 5 days	Yes
Primary	To assess the proportion of subjects with reduction in HBV DNA by = 2 log10 or to undetectable level (< 400 copies/mL)		at Week 48	No
Secondary	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		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 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 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