Current therapy for chronic hepatitis B is suboptimal as a result of limited d urable response rates, cumulative viral resistance, and/or poor tolerability. Te lbivudine has potent antiviral activity against hepatitis B virus (HBV) in vitro and in the woodchuck model and has a promising preclinical safety profile. In t his first clinical study of telbivudine, safety, antiviral activity, and pharmac ok inetics were assessed in 43 adults with hepatitis B e antigen-positive chron ic hepatitis B. This placebocontrolled dose-escalation trial investigated 6 tel bivudine daily dosing levels (25, 50, 100, 200, 400, and 800 mg/d); treatment wa s given for 4 weeks, with 12 weeks’follow-up. Serum HBV DNA levels were monito red via quantitative polymerase chain reaction. The results indicate that telbiv udine was well tolerated at all dosing levels, with no dose-related or treatmen t-related clinical or laboratory adverse events. telbivudine plasma pharmacokin etics were dose-proportional within the studied dose range. Marked dose-relate d antiviral activity was evident, with a maximum at telbivudine doses of 400 mg/ d or more. In the 800mg/d cohort, the mean HBV DNA reduction was 3.75 log10 copi es/mL at week 4, comprising a 99.98%reduction in serum viral load. Correspondin gly, posttreatment return of viral load was slowest in the high-dose groups. Vi ral dynamic analyses suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helped refine selection of the optimal dose. In c onclusion, these results support expanded clinical studies of this new agent for the treatment of hepatitis B. Current therapy for chronic hepatitis B is suboptimal as a result of limited d urable response rates, cumulative viral resistance, and / or poor tolerability. Te lbivudine has potent antiviral activity against hepatitis B virus (HBV) in vitro and in the woodchuck model and has a promising preclinical safety profile. In t his first clinical study of telbivudine, safety, antiviral activity, and pharmac ok inetics were assessed in 43 adults with hepatitis B e antigen-positive chron ic hepatitis B. This placebocontrolled dose-escalation trial investigated 6 tel bivudine daily dosing levels (25, 50, 100, 200, 400, and 800 mg / d); treatment wa s given for 4 weeks with 12 weeks’follow-up. Serum HBV DNA levels were monito red via quantitative polymerase chain reaction . The results indicate that telbiv udine was well tolerated at all dosing levels, with no dose-related or treatmen t-related clinical or laboratory adverse events. Telbivudine plasma pharmacokin etics were dose-proportional within t Marked dose-relate d antiviral activity was evident, with a maximum at telbivudine doses of 400 mg / d or more. In the 800 mg / d cohort, the mean HBV DNA reduction was 3.75 log10 copi es / mL at week 4, comprising a 99.98% reduction in serum viral load. Correspondin gly, posttreatment return of viral load was slowest in the high-dose groups. Vi ral dynamic analyzes suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helps refine selection of the optimal dose. In c onclusion, these results support expanded clinical studies of this new agent for the treatment of hepatitis B