Abstract
GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A, demonstrates potent activity against HCV genotypes 1–6 and improved coverage against commonly encountered NS3 resistance-associated variants (RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1–4 infection. Patients with genotype 1–4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. GS-9857 was well tolerated; all reported adverse events (AEs) were mild or moderate in severity. Diarrhoea and headache were the most commonly reported AEs. Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated potent antiviral activity in patients with chronic HCV infection, achieving mean and median maximum reductions in HCV RNA of ≥3 log10 IU/mL following administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 infection. The antiviral activity of GS-9857 was unaffected by the presence of pretreatment NS3 RAVs. In patients with genotype 1–4 infection, GS-9857 exhibited linear PK and was associated with a median half-life of 29–42 h, supporting once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile of GS-9857 support its further evaluation for treatment of patients with chronic HCV infection.
Original language | English (US) |
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Pages (from-to) | 614-622 |
Number of pages | 9 |
Journal | Journal of Viral Hepatitis |
Volume | 23 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2016 |
Keywords
- GS-9857
- NS3/4A protease inhibitor
- hepatitis C virus
ASJC Scopus subject areas
- Infectious Diseases
- Virology
- Hepatology