Antiviral Activity and Safety of Lb80380 in Hepatitis B E Antigen–Positive Chronic Hepatitis B Patients With Lamivudine-Resistant Disease

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Abstract
We aimed to determine the antiviral activity and safety of a new nucleotide analogue, LB80380, in chronic hepatitis B (CHB) patients with lamivudine-resistant virus. Sixty-five patients with lamivudine-resistant virus were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg) of LB80380. LB80380 was given together with lamivudine for the first 4 weeks, followed by 8 weeks of LB80380 monotherapy. This was then followed by 24 weeks of adefovir. Hepatitis B virus (HBV) DNA levels, serology, liver biochemistry, and safety were monitored. The extent of the HBV DNA reduction at week 12 was dose-dependent. The mean reduction from baseline was 2.81, 3.21, 3.92, 4.16, and 4.00 log10 copies/mL for the five ascending dose groups. The dose-proportionate effect was statistically significant ( P < 0.001) with a decrease of HBV DNA levels by an average of 1.54 log10 copies/mL for every 1-unit increase in log10 dose of LB80380. In 93.4% of patients, HBV DNA decreased by >2 log10 copies/mL, and 11.5% of patients had undetectable HBV DNA levels ( Conclusion: LB80380 at doses of up to 240 mg is safe, well tolerated, and effective at reducing viral load in CHB patients with lamivudine-resistant virus for a period of 12 weeks. (Hepatology 2010.)