The study consisted of 7 days of monotherapy with TMC435 (200 mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from day 8 with a follow-up period up to days 37-42.
Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary end point at day 8, the mean (卤 standard error) change in plasma HCV ribonucleic acid (log10 IU/ml) from baseline was the greatest for genotypes 6 (鈭?.35 卤 0.29) and 4 (鈭?.52 卤 0.43), followed by genotypes 2 (鈭?.73 卤 0.71) and 5 (鈭?.19 卤 0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period.
The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated.