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


METHODS
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 20mg in single or divided doses for 28 days and were followed up for approximately 12 weeks after cessation of treatment.


RESULTS
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 (5mg BID vs 10mg QD, 10mg BID vs 20mg 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.


CONCLUSIONS
Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety profile.
Soon
Danny K W
DK
Lilly-NUS Centre for Clinical Pharmacology, Level 6 Clinical Research Centre (MD11), National University of Singapore, 10 Medical Drive, Singapore, Singapore 117597.
Lowe
Stephen L
SL
Teng
Choo Hua
CH
Yeo
Kwee Poo
KP
McGill
James
J
Wise
Stephen D
SD
D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
C461207:2-amino-6-(4-methoxyphenylthio)-9-(2-(phosphonomethoxy)ethyl)purine bis(2,2,2-trifluoroethyl) ester; D000998:Antiviral Agents; D011687:Purines