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

Study Overview
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Brief Summary
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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

Official Title
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A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of chronic hepatitis B infection by ALL of the following: Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy Positive for HBeAg OR negative for HBeAg 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Entecavir (0.1 mg)<br> | Drug: Entecavir<br>* Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks<br>* Other names: BMS-200475;|
| Experimental: Entecavir (0.5 mg)<br> | Drug: Entecavir<br>* Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks<br>* Other names: BMS-200475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48 |  | Week 48 | 
| Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48 |  | Week 48 | 
| Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48 |  | Week 48 | 
| Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48 |  | Week 48 | 
| 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 | 
| 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 | 
| Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug |  | Week 72 | 
| 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 | 
| Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis |  | Week 52 | 
| 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) | 
| 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) | 
| Mutation of HBV DNA polymerase at Week 48 from baseline |  | Baseline, Week 48 | 
| 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 | 
| 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 |