کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3314415 1211197 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phase 2 study of the combination of merimepodib with peginterferon-α2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Phase 2 study of the combination of merimepodib with peginterferon-α2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C
چکیده انگلیسی

Background/AimsWhile combination of peginterferon-α (PEG-IFN) and ribavirin (RBV) therapy is the current standard of care for chronic hepatitis C (CHC), only 44–51% of genotype-1 patients achieve a sustained virological response (SVR), and both agents produce treatment-limiting toxicities. In the hepatitis C virus (HCV) replicon system, merimepodib (MMPD), a novel, selective inhibitor of inosine monophosphate dehydrogenase, has shown potent antiviral effects.MethodsThis randomized, placebo-controlled, double-blind study evaluated the safety and antiviral activity of PEG-IFN-α2b and RBV combined with either placebo, 25 mg MMPD every 12 h (q12h), or 50 mg MMPD q12h in interferon-α (IFN) and RBV nonresponders. After 24 weeks of treatment, subjects with undetectable HCV RNA were proposed to continue assigned treatment for up to 24 additional weeks.ResultsThe PEG-IFN-α, RBV, and MMPD combination was well tolerated at both doses. After 24 weeks, the proportion of HCV RNA undetectable subjects was 8/11 (73%) in the 50-mg MMPD group, 2/10 (20%) in the 25-mg MMPD group, and 3/10 (30%) in the placebo group (P = 0.02, Jonckheere-Terpstra test for increasing dose response). Ten subjects entered and completed an extension study, at Week 48, 2 of 2 (100%) of the 25-mg and 3 of 5 (60%) of the 50-mg subjects remained HCV RNA undetectable, compared with 3 of 3 (100%) of the placebo subjects. At Follow-up Week 24, 2 (100%) of the 25-mg , and 1 (25%) of the 50-mg subjects remained undetectable, compared with 1 (33%) of the placebo subjects. Pharmacokinetic and pharmacodynamic analyses showed a correlation between MMPD exposure and early virological response at week 12, but not with hemoglobin decreases often associated with RBV.ConclusionsIn conclusion, PEG-IFN-α2b and RBV combined with 50 mg MMPD q12h was well tolerated and induced virological response with undetectable HCV RNA in IFN-α and RBV nonresponders.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 47, Issue 4, October 2007, Pages 476–483
نویسندگان
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