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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
Time frame: 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
Time frame: 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
Time frame: Week 48
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
Time frame: Baseline, Week 48
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
Time frame: Week 48
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48
Time frame: 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
Time frame: Week 48
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
Time frame: Week 48
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
Time frame: 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
Time frame: Baseline, Week 48
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Time frame: Week 52
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
Time frame: 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.
Time frame: Week 48, or at end of dosing (up to Week 52)
Mutation of HBV DNA polymerase at Week 48 from baseline
Time frame: Baseline, Week 48
Plasma concentrations of entecavir at selected time points during the treatment period
Time frame: 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
Time frame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36