期刊
ANTIVIRAL THERAPY
卷 16, 期 7, 页码 1021-1033出版社
INT MEDICAL PRESS LTD
DOI: 10.3851/IMP1894
关键词
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资金
- Tibotec Pharmaceuticals
- Schering-Plough (MSD)
- Roche
- Merck
- Bristol-Myers Squibb
- Vertex
- Astra/Arrow
- Novartis
- Human Genome Sciences
- Boehringer Ingelheim
- Valeant
- PRA International
- Vertex Pharmaceuticals
- Gilead
- Schering-Plough
- Gilead Sciences
- Pfizer
- Janssen-Cilag
Background: Antiviral activity of TMC435, an oral, once-daily, HCV NS3/4A protease inhibitor, was evaluated with pegylated interferon-alpha 2a/ribavirin (P/R) in HCV genotype-1 patients. Methods: Optimal Protease inhibitor Enhancement of Response to TherApy (OPERA-1; TMC435-C201; NCT00561353) is a Phase IIa, randomized, placebo-controlled study. Treatment-naive patients (n=74) received 25, 75 or 200 mg TMC435 once daily, or placebo for 7 days followed by 21 days of triple therapy with P/R, or triple therapy for 28 days. Treatment-experienced patients (n=37; 56.8% with cirrhosis) received 75, 150 or 200 mg TMC435 once daily, or placebo with P/R for 28 days. Patients continued P/R up to week 48. Results: Treatment-naive patients who received initial monotherapy had a rapid decline in HCV RNA by day 3. At day 7, HCV RNA reductions were greatest for the 75 and 200 mg doses (0.02, -2.63, -3.43 and -4.13 log(10) IU/ml for placebo, and TMC435 25, 75 and 200 mg, respectively). At day 28, all patients who received triple therapy with TMC435 75 or 200 mg had HCV RNA.:25 IU/ml versus 4/9 for placebo. In total, 18/28 treatment-experienced patients (9/9 prior relapsers, 9/19 non-responders) who received TMC435 had HCV RNA<25 IU/ml at day 28 versus 0/9 for placebo; similar results were observed for the 150 and 200 mg doses. Most adverse events were grade 1/2. No relevant changes in laboratory parameters occurred, except mild and reversible bilirubin elevations, mostly at the 200 mg dose. Conclusions: Once-daily TMC435 with P/R showed potent, dose-dependent antiviral activity over 28 days, and had a favourable tolerability profile.
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