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

简要总结

主要结局

次要结局

• 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)