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Abstract Details
Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C
Fred Poordad, M.D., Eric Lawitz, M.D., Kris V. Kowdley, M.D., Daniel E. Cohen, M.D., Thomas Podsadecki, M.D., Sara Siggelkow, R.N., Michele Heckaman, M.S., Lois Larsen, Ph.D., Rajeev Menon, Ph.D., Gennadiy Koev, Ph.D., Rakesh Tripathi, M.S., Tami Pilot-Matias, Ph.D., and Barry Bernstein, M.D. N Engl J Med 2013; 368:45-53January 3, 2013DOI: 10.1056/NEJMoa120880
SOURCE INFORMATION
From the University of Texas Health Science Center, San Antonio (F.P., E.L.); the Digestive Disease Institute, Virginia Mason Medical Center, Seattle (K.V.K.); and Abbott, Abbott Park, IL (D.E.C., T.P., S.S., M.H., L.L., R.M., G.K., R.T., T.P.-M., B.B.).
BACKGROUND
There is a need for interferon-free treatment regimens for hepatitis C virus (HCV) infection. The goal of this study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor, combined with low-dose ritonavir (ABT-450/r), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and ribavirin, for the treatment of HCV infection.
METHODS
We conducted a 12-week, phase 2a, open-label study involving patients who had HCV genotype 1 infection without cirrhosis. All patients received ABT-333 (400 mg twice daily) and ribavirin (1000 to 1200 mg per day) and one of two daily doses of ABT-450/r. Groups 1 and 2 included previously untreated patients; group 1 received 250 mg of ABT-450 and 100 mg of ritonavir, and group 2 received 150 mg and 100 mg, respectively. Group 3, which included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin, received daily doses of 150 mg of ABT-450 and 100 mg of ritonavir. The primary end point was an undetectable level of HCV RNA from week 4 through week 12 (extended rapid virologic response).
RESULTS
A total of 17 of the 19 patients in group 1 (89%) and 11 of the 14 in group 2 (79%) had an extended rapid virologic response; a sustained virologic response 12 weeks after the end of treatment was achieved in 95% and 93% of the patients, respectively. In group 3, 10 of 17 patients (59%) had an extended rapid virologic response, and 8 (47%) had a sustained virologic response 12 weeks after therapy; 6 patients had virologic breakthrough, and 3 had a relapse. Adverse events included abnormalities in liver-function tests, fatigue, nausea, headache, dizziness, insomnia, pruritus, rash, and vomiting.
CONCLUSIONS
This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin may be effective for treatment of HCV genotype 1 infection. (Funded by Abbott; ClinicalTrials.gov number, NCT01306617.)