Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial

• Published in: Antiviral therapy 2011-01, Vol.16 (7), p.1021-1033
• Main Authors: MANNS, Michael, REESINK, Henk, SEKAR, Vanitha, SIMMEN, Kenneth, VERLOES, Rene, BERG, Thomas, DUSHEIKO, Geoffrey, FLISIAK, Robert, MARCELLIN, Patrick, MORENO, Christophe, LENZ, Oliver, MEYVISCH, Paul, PEETERS, Monika
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Bilirubin - analysis; Biological and medical sciences; Double-Blind Method; Drug Therapy, Combination; Female; Genotype; Hepacivirus - drug effects; Hepatitis C - drug therapy; Hepatitis C - virology; Heterocyclic Compounds, 3-Ring - administration & dosage; Heterocyclic Compounds, 3-Ring - adverse effects; Heterocyclic Compounds, 3-Ring - therapeutic use; Human viral diseases; Humans; Infectious diseases; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - therapeutic use; Protease Inhibitors - administration & dosage; Protease Inhibitors - adverse effects; Protease Inhibitors - therapeutic use; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Ribavirin - administration & dosage; Ribavirin - pharmacology; Ribavirin - therapeutic use; RNA, Viral - blood; Simeprevir; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Viral diseases; Viral hepatitis; Viral Load
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP1894

Antiviral activity of TMC435, an oral, once-daily, HCV NS3/4A protease inhibitor, was evaluated with pegylated interferon-α2a/ribavirin (P/R) in HCV genotype-1 patients. 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. 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