Clevudine is a
nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant
antiviral activity. The present study was conducted to assess the degree and durability of the
antiviral response to 12 weeks of
clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with
HBeAg-positive
chronic hepatitis B were randomized to placebo (n=32), 30-mg
clevudine (n=32), and 50-mg
clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-
therapy. Median serum hepatitis B virus
DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg
clevudine, and 50-mg
clevudine groups, respectively (P < .0001). Posttreatment
antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-
therapy and 2.28 and 1.40 log10 reductions at week 24 off-
therapies in the 30- and 50-mg
clevudine groups, respectively. Median serum
alanine aminotransferase (ALT) levels decreased markedly from baseline during
clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-
therapy in the two
clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion,
clevudine showed potent
antiviral activity during
therapy and induced a sustained posttreatment
antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels.