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GS‐9857 in patients with chronic hepatitis C virus genotype 1–4 infection: a randomized, double‐blind, dose‐ranging phase 1 study
Author(s) -
RodriguezTorres M.,
Glass S.,
Hill J.,
Freilich B.,
Hassman D.,
Di Bisceglie A. M.,
Taylor J. G.,
Kirby B. J.,
DvorySobol H.,
Yang J. C.,
An D.,
Stamm L. M.,
Brainard D. M.,
Kim S.,
Krefetz D.,
Smith W.,
Marbury T.,
Lawitz E.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12527
Subject(s) - tolerability , medicine , hepatitis c virus , gastroenterology , dosing , adverse effect , placebo , pharmacokinetics , genotype , dose ranging study , hepacivirus , hepatitis c , virus , immunology , biology , pathology , double blind , biochemistry , alternative medicine , gene
Summary 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 NS 3 resistance‐associated variants ( RAV s). 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 log 10 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 NS 3 RAV s. 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.