{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T23:49:30Z","timestamp":1772063370364,"version":"3.50.1"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4079,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Current 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 <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. 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 \u00d7 10<jats:sup>6<\/jats:sup> 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 log<jats:sub>10<\/jats:sub> copies\/mL. After 28 days, the median HBV DNA log<jats:sub>10<\/jats:sub> change from baseline was \u22122.5, \u22122.7, \u22123.0, and \u22122.6 log<jats:sub>10<\/jats:sub>. Six months after dosing, median changes from baseline were \u22121.2, \u22121.4, \u22122.7 and \u22121.7 log<jats:sub>10<\/jats:sub> 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. <jats:underline>In conclusion,<\/jats:underline> these results demonstrate the tolerability and potent activity of clevudine in HBV-infected patients and support further clinical study. 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