[A study of the dosage and efficacy of entecavir for treating hepatitis B virus].

ABSTRACT

OBJECTIVE: To evaluate the antiviral activity and safety of entecavir in patients with chronic HBV infection as a preliminarily step in selecting 0.1 mg or 0.5 mg as a better dosage for a further large scale clinical trial. METHODS: This was a randomized, double-blinded, placebo-controlled and dose-ranging trial of entecavir usage in 212 patients with chronic HBV infection. The patients were randomly assigned to 3 groups 0.1 mg entecavir (69), 0.5 mg entecavir (72) and, placebo (71) groups and treated for 28 days. The patients were then followed for 56 days without treatment. RESULTS: The proportion of subjects who achieved the primary endpoint at day 28, with their HBV DNA level decreased >2 log or undetectable, was significantly greater in the entecavir 0.1 mg and 0.5 mg dose groups compared with the placebo group (P < 0.01 for both comparisons). The mean change from baseline in HBV DNA levels at day 28 was greater for entecavir 0.1mg and 0.5 mg groups compared with the placebo group (both P < 0.01). The mean change from baseline in HBV DNA levels at day 28 for entecavir 0.5 mg group was greater than that of the entecavir 0.1 mg group (P < 0.01). During the 56-day post-dosing follow-up phase, the entecavir 0.5 mg group was associated with greater and more sustained suppression of viral replication than the entecavir 0.1 mg group (P < 0.01). There were no clinically meaningful differences in the incidence of any adverse events between the entecavir dosing and the placebo groups. CONCLUSION: Entecavir at both 0.1 mg and 0.5 mg doses demonstrated superior antiviral activity compared with a placebo. Since the entecavir 0.5 mg dose appears to have greater antiviral activity than the 0.1 mg dose and with a comparable safety and tolerability profile, the 0.5 mg entecavir dose could be used in further trials.