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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
Author(s) -
LIM S. G.,
LEUNG N.,
HANN H. W. L.,
LAU G. K. K.,
TREPO C.,
MOMMEJAMARIN H.,
MOXHAM C.,
SORBEL J.,
SNOW A.,
BLUM M. R.,
ROUSSEAU F.,
MARCELLIN P.
Publication year - 2008
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2008.03686.x
Subject(s) - medicine , pharmacokinetics , viral load , pharmacodynamics , adverse effect , gastroenterology , chronic hepatitis , virology , pharmacology , virus
Summary 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.