Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease

Man Fung Yuen, KwangHyub Han, Soon Ho Um, Seung Kew Yoon, Hye Ryon Kim, John Kim, Chung Ryeol Kim, Ching Lung Lai

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 (<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.

Original languageEnglish
Pages (from-to)767-776
Number of pages10
JournalHepatology
Volume51
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

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Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Antiviral Agents
Safety
Hepatitis B virus
DNA
Viruses
Serology
Viral Load
Alanine Transaminase
Biochemistry
Nucleotides
Liver
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Yuen, Man Fung ; Han, KwangHyub ; Um, Soon Ho ; Yoon, Seung Kew ; Kim, Hye Ryon ; Kim, John ; Kim, Chung Ryeol ; Lai, Ching Lung. / Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease. In: Hepatology. 2010 ; Vol. 51, No. 3. pp. 767-776.
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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 (<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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Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease. / Yuen, Man Fung; Han, KwangHyub; Um, Soon Ho; Yoon, Seung Kew; Kim, Hye Ryon; Kim, John; Kim, Chung Ryeol; Lai, Ching Lung.

In: Hepatology, Vol. 51, No. 3, 01.03.2010, p. 767-776.

Research output: Contribution to journalArticle

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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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