TY - JOUR
T1 - Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease
AU - Yuen, Man Fung
AU - Han, Kwang Hyub
AU - Um, Soon Ho
AU - Yoon, Seung Kew
AU - Kim, Hye Ryon
AU - Kim, John
AU - Kim, Chung Ryeol
AU - Lai, Ching Lung
PY - 2010/3
Y1 - 2010/3
N2 - 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 (<300 copies/mL) by week 12. HBV DNA suppression was maintained during the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and normalization of alanine aminotransferase were seen in 14.6% and 24.6% of patients, respectively, at week 12; 44.6% of patients experienced mild and self-limiting adverse events, none of which were attributed to the study drug. 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.
AB - 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 (<300 copies/mL) by week 12. HBV DNA suppression was maintained during the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and normalization of alanine aminotransferase were seen in 14.6% and 24.6% of patients, respectively, at week 12; 44.6% of patients experienced mild and self-limiting adverse events, none of which were attributed to the study drug. 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.
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U2 - 10.1002/hep.23462
DO - 10.1002/hep.23462
M3 - Article
C2 - 20091678
AN - SCOPUS:77950606642
VL - 51
SP - 767
EP - 776
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 3
ER -