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

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TitleAntiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease
AuthorsYuen, MF3
Han, KH4
Um, SH5
Yoon, SK1
Kim, HR2
Kim, J2
Kim, CR2
Lai, CL3
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
CitationHepatology, 2010, v. 51 n. 3, p. 767-776 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.23462
AbstractWe 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. Copyright © 2010 by the American Association for the Study of Liver Diseases.
ISSN0270-9139
2011 Impact Factor: 11.665
2011 SCImago Journal Rankings: 1.278
DOIhttp://dx.doi.org/10.1002/hep.23462
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYuen, MF
dc.contributor.authorHan, KH
dc.contributor.authorUm, SH
dc.contributor.authorYoon, SK
dc.contributor.authorKim, HR
dc.contributor.authorKim, J
dc.contributor.authorKim, CR
dc.contributor.authorLai, CL
dc.date.accessioned2012-09-05T05:29:50Z
dc.date.available2012-09-05T05:29:50Z
dc.date.issued2010
dc.description.abstractWe 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. Copyright © 2010 by the American Association for the Study of Liver Diseases.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationHepatology, 2010, v. 51 n. 3, p. 767-776 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.23462
dc.identifier.doihttp://dx.doi.org/10.1002/hep.23462
dc.identifier.epage776
dc.identifier.issn0270-9139
2011 Impact Factor: 11.665
2011 SCImago Journal Rankings: 1.278
dc.identifier.issue3
dc.identifier.pmid20091678
dc.identifier.scopuseid_2-s2.0-77950606642
dc.identifier.spage767
dc.identifier.urihttp://hdl.handle.net/10722/163301
dc.identifier.volume51
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
dc.publisher.placeUnited States
dc.relation.ispartofHepatology
dc.relation.referencesReferences in Scopus
dc.subject.meshAdult
dc.subject.meshDna, Viral - Blood
dc.subject.meshDrug Resistance, Viral
dc.subject.meshFemale
dc.subject.meshGuanine - Adverse Effects - Analogs & Derivatives - Therapeutic Use
dc.subject.meshHepatitis B E Antigens - Blood
dc.subject.meshHepatitis B Virus - Genetics
dc.subject.meshHepatitis B, Chronic - Blood - Drug Therapy - Immunology
dc.subject.meshHumans
dc.subject.meshLamivudine - Therapeutic Use
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPhosphonic Acids - Adverse Effects - Therapeutic Use
dc.subject.meshReverse Transcriptase Inhibitors - Therapeutic Use
dc.subject.meshYoung Adult
dc.titleAntiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease
dc.typeArticle
Author Affiliations
  1. The Catholic University of Korea
  2. LG
  3. The University of Hong Kong
  4. Yonsei University College of Medicine
  5. Korea University