Safety and efficacy of alamifovir in patients with chronic hepatitis B virus infection

Abstract

Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. A randomised, placebo controlled, dose escalation study of oral alamifovir was conducted in 66 chronic hepatitis B infected patients who were selected based on stable HBV DNA (>10 5 copies/ml), with no significant liver pathology. They received either placebo or alamifovir at a total daily dose ranging from 2.5 to 20 mg in single or divided doses for 28 days and were followed up for approximately 12 weeks after cessation of treatment. All doses showed significant antiviral activity, with mean plasma viral load reductions ranging from 1.5 to 2.6 log 10 after 28 days of dosing. Once and twice daily regimen for the same daily dose (5 mg BID vs 10 mg QD, 10 mg BID vs 20 mg QD) showed no apparent difference in the rate and extent of viral decline, or viral reduction at day 28. Post-treatment viral suppression was dose dependent. There were no serious adverse events attributable to study drug, nor were significant dose related events identified. Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety profile. © 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.