12 In an in vitro experiment, this drug has also been shown to be effective against HBV mutants click here resistant to lamivudine, adefovir, entecavir, and telbivudine.13 We report the results of an open-label, multicenter dose escalation study to assess the antiviral activity and safety of LB80380 for 12 weeks in CHB patients with lamivudine-resistant disease. AE, adverse event; ALT, alanine aminotransferase; CHB, chronic hepatitis B; CI, confidence interval; CrCl, creatinine clearance; DLT, dose-limiting

toxicity; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; NA, nucleoside/nucleotide analog; PP, per-protocol;

SD, standard deviation; ULN, upper limit of normal. This study was a phase II, open-label, multicenter, dose escalation study to evaluate the antiviral activity learn more and safety of LB80380 during a 12-week treatment period. This study was conducted at four centers in Hong Kong and Korea. Because the efficacy assessment was descriptive, the sample size calculation was based on the accuracy of the confidence interval (CI) for the primary efficacy parameter (mean reduction in HBV DNA at 12 weeks on the log10 scale). The accuracy was measured by the width of the 95% CI. The two-sided 95% CI for the mean was estimated with the assumption that the distribution of the reduction on the log scale is symmetric and normally

distributed. Assuming a potential dropout rate of at most 25% over the treatment period of 12 weeks, a minimum of twelve patients were to be enrolled into each dose group to ensure that at least nine would be evaluable. The treatment period was divided into two parts: an initial 4-week treatment period (part MCE公司 1) during which dose escalation was assessed, followed by an 8-week extension period (part 2). The treatment period was followed by a 24-week follow-up period. During the initial 4 weeks of the treatment period (part 1), patients received LB80380 together with lamivudine 100 mg once daily. The overlapping 4-week period of LB80380 and lamivudine was designed to minimize the risk of hepatitis flares that might occur if the therapy was switched directly to LB80380 monotherapy. Five doses of LB80380 were planned: 30 mg (group 1); 60 mg (group 2); 90 mg (group 3); 150 mg (group 4), and 240 mg (group 5). After completion of 4-week dosing at each level of LB80380 combined with lamivudine 100 mg in part 1, patients were given only LB80380 at the same dose for an additional 8 weeks in part 2, unless more than two patients in the group experienced dose-limiting toxicity (DLT) during part 1.