Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti-viral activity of clevudine for 12 weeks in patients with chronic hepatitis B.

Abstract

BACKGROUND:

Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics.

AIM:

To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor.

METHODS:

A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off-treatment follow-up. Patients had chronic HBV infection, were nucleoside-naïve without co-infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method.

RESULTS:

A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was -3.2, -3.7 and -4.2 log(10) copies/mL (-0.64, -0.74 and -0.84 log(10) IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half-life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound.

CONCLUSION:

Clevudine appears to be a potent and tolerable (over 12 weeks) anti-viral and the optimal dosage appears to be 30 mg once daily.

• Authors: S G Lim, N Leung, H W L Hann, G K K Lau, C Trepo, H Mommeja-Marin, C Moxham, J Sorbel, A Snow, M R Blum, F Rousseau, P Marcellin
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 27 Issue 12 Pg. 1282-92 (Jun 2008) ISSN: 1365-2036 [Electronic] England
• PMID: 18363895 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Antiviral Agents
• Arabinofuranosyluracil
• clevudine

Topics

• Adolescent
• Adult
• Antibodies, Viral (drug effects)
• Antiviral Agents (administration & dosage, pharmacokinetics)
• Arabinofuranosyluracil (administration & dosage, analogs & derivatives, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Genotype
• Hepatitis B, Chronic (drug therapy)
• Humans
• Male
• Middle Aged
• Treatment Outcome