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Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders
Author(s) -
Rustgi Vinod K.,
Lee William M.,
Lawitz Eric,
Gordon Stuart C.,
Afdhal Nezam,
Poordad Fred,
Bonkovsky Herbert L.,
Bengtsson Leif,
Chandorkar Gurudatt,
Harding Matthew,
McNair Lindsay,
Aalyson Molly,
Alam John,
Kauffman Robert,
Gharakhanian Shahin,
McHutchison John G.
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23204
Subject(s) - ribavirin , medicine , tolerability , pegylated interferon , gastroenterology , placebo , adverse effect , hepatitis c , alpha interferon , hepatitis c virus , clinical endpoint , interferon alfa , randomized controlled trial , pharmacology , immunology , interferon , virus , pathology , alternative medicine
Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg‐IFN‐alfa‐2a) and ribavirin (RBV). We conducted a randomized, double‐blind, multicenter, phase 2b study to evaluate the antiviral activity, safety, and tolerability of MMPD in combination with Peg‐IFN‐alfa‐2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg‐IFN and RBV. Patients received 50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg‐IFN‐alfa‐2a and RBV, for 24 weeks. Patients with a 2‐log or more decrease from baseline or undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to continue Peg‐IFN‐alfa‐2a and RBV for a further 24 weeks, followed by 24 weeks of follow‐up. The primary efficacy endpoint was sustained virological response (SVR) rate at week 72 in all randomized patients who received at least one dose of study drug and had a history of nonresponse to standard therapy. A total of 354 patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to 100 mg MMPD), and 286 completed the core study. The proportion of patients who achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD, 4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo ( P = 0.8431). Adverse‐event profiles for the MMPD combination groups were similar to that for Peg‐IFN‐alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia were more common in patients taking MMPD. Conclusion: The addition of MMPD to Peg‐IFN‐alfa‐2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR. (H EPATOLOGY 2009.)