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Article: A phase II dose-escalating trial of clevudine in patients with chronic hepatitis B

TitleA phase II dose-escalating trial of clevudine in patients with chronic hepatitis B
Authors
Issue Date2004
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2004, v. 40 n. 1, p. 140-148 How to Cite?
AbstractCurrent therapies available for the treatment of chronic hepatitis B are limited in their ability to result in a cure. Clevudine is a new pyrimidine analog with potent anti-hepatitis B virus (HBV) activity in vitro. A multicenter dose-escalation study evaluated clevudine at 10, 50, 100, and 200 mg once daily for 28 days. Eligible patients had HBV DNA levels of 3 × 106 copies/mL or more, had not undergone nucleoside treatment, and were without human immunodeficiency or hepatitis C virus coinfection. Thirty-two patients were enrolled (5, 10, 10, and 7 patients in the 10-, 50-, 100-, and 200-mg dose groups, respectively), 81% were male, 81% Asian, and 88% were hepatitis Be antigen (HBeAg) positive at baseline. Median pretreatment serum HBV DNA levels ranged from 7.3 to 8.8 log10 copies/mL. After 28 days, the median HBV DNA log10 change from baseline was −2.5, −2.7, −3.0, and −2.6 log10. Six months after dosing, median changes from baseline were −1.2, −1.4, −2.7 and −1.7 log10 in the 10-, 50-, 100-, and 200-mg cohorts, respectively. Six of 27 patients lost HBeAg, and 3 of 27 patients seroconverted to HBe antibody. Clevudine was well tolerated, with no dose-limiting toxicities. A transient increase in alanine aminotransferase of up to 7.8 times the upper limit of normal (increase ranged from 20 to 186 IU/L) was observed in six patients in the 100-mg cohort, without signs of liver failure. These increases were associated with improved viral suppression. The pharmacokinetic profile of clevudine was proportional to the dose. In conclusion, these results demonstrate the tolerability and potent activity of clevudine in HBV-infected patients and support further clinical study. (HEPATOLOGY 2004;40:140–148.)
Persistent Identifierhttp://hdl.handle.net/10722/224813
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752

 

DC FieldValueLanguage
dc.contributor.authorMarcellin, P-
dc.contributor.authorMommeja-Marin, H-
dc.contributor.authorSacks, SL-
dc.contributor.authorLau, GKK-
dc.contributor.authorSereni, D-
dc.contributor.authorBronowicki, JP-
dc.contributor.authorConway, B-
dc.contributor.authorTrepo, C-
dc.contributor.authorBlum, MR-
dc.contributor.authorYoo, BC-
dc.contributor.authorMondou, E-
dc.contributor.authorSorbel, Jeff-
dc.contributor.authorSnow, A-
dc.contributor.authorRousseau, F-
dc.contributor.authorLee, HS-
dc.date.accessioned2016-04-18T01:25:13Z-
dc.date.available2016-04-18T01:25:13Z-
dc.date.issued2004-
dc.identifier.citationHepatology, 2004, v. 40 n. 1, p. 140-148-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10722/224813-
dc.description.abstractCurrent therapies available for the treatment of chronic hepatitis B are limited in their ability to result in a cure. Clevudine is a new pyrimidine analog with potent anti-hepatitis B virus (HBV) activity in vitro. A multicenter dose-escalation study evaluated clevudine at 10, 50, 100, and 200 mg once daily for 28 days. Eligible patients had HBV DNA levels of 3 × 106 copies/mL or more, had not undergone nucleoside treatment, and were without human immunodeficiency or hepatitis C virus coinfection. Thirty-two patients were enrolled (5, 10, 10, and 7 patients in the 10-, 50-, 100-, and 200-mg dose groups, respectively), 81% were male, 81% Asian, and 88% were hepatitis Be antigen (HBeAg) positive at baseline. Median pretreatment serum HBV DNA levels ranged from 7.3 to 8.8 log10 copies/mL. After 28 days, the median HBV DNA log10 change from baseline was −2.5, −2.7, −3.0, and −2.6 log10. Six months after dosing, median changes from baseline were −1.2, −1.4, −2.7 and −1.7 log10 in the 10-, 50-, 100-, and 200-mg cohorts, respectively. Six of 27 patients lost HBeAg, and 3 of 27 patients seroconverted to HBe antibody. Clevudine was well tolerated, with no dose-limiting toxicities. A transient increase in alanine aminotransferase of up to 7.8 times the upper limit of normal (increase ranged from 20 to 186 IU/L) was observed in six patients in the 100-mg cohort, without signs of liver failure. These increases were associated with improved viral suppression. The pharmacokinetic profile of clevudine was proportional to the dose. In conclusion, these results demonstrate the tolerability and potent activity of clevudine in HBV-infected patients and support further clinical study. (HEPATOLOGY 2004;40:140–148.)-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatology-
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.subject.meshAlanine Transaminase blood-
dc.subject.meshAntibodies, Viral analysis-
dc.subject.meshAntiviral Agents - administration & dosage - adverse effects - pharmacokinetics-
dc.subject.meshArabinofuranosyluracil - administration & dosage - adverse effects - analogs & derivatives - pharmacokinetics-
dc.subject.meshHepatitis B, Chronic - blood - drug therapy - immunology - virology-
dc.titleA phase II dose-escalating trial of clevudine in patients with chronic hepatitis B-
dc.typeArticle-
dc.identifier.emailLau, GKK: gkklau@netvigator.com-
dc.identifier.doi10.1002/hep.20257-
dc.identifier.pmid15239097-
dc.identifier.hkuros100604-
dc.identifier.volume40-
dc.identifier.issue1-
dc.identifier.spage140-
dc.identifier.epage148-
dc.publisher.placeUnited States-

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