BACKGROUND/AIMS: VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase with sub-micromolar IC(50) values versus genotype 1a/1b replicons. METHODS: The antiviral activity, pharmacokinetics and tolerability of VCH-759 administered as monotherapy for 10 days with a 14 day follow-up period were evaluated in 31 treatment-nai ve genotype 1 participants. Three cohorts received: 400mg thrice (t.i.d.), 800 mg twice (b.i.d.), 800 mg t.i.d or placebo. RESULTS: VCH-759 was well tolerated with the most frequent adverse event being gastrointestinal upset in both the active and placebo groups attributable, in part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma levels were at or above the IC(90) (non protein-adjusted) for all dosing regimens. The mean maximal decrease in HCV RNA log(10) (IU/mL) was 1.97, 2.30 and 2.46 for 400mg t.i.d., 800 mg b.i.d. and 800 mg t.i.d. doses. Viral polymerase genotypic sequencing revealed emergence of HCV variants in a majority of participants that coincided with on-treatment viral rebound. CONCLUSIONS: VCH-759 was well tolerated and achieved a> or =2 log(10) decline in HCV RNA with 800 mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was observed and associated with resistant variants. This data supports further evaluation of VCH-759 in combination with interferon-ribavirin treatment.
BACKGROUND/AIMS: VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase with sub-micromolar IC(50) values versus genotype 1a/1b replicons. METHODS: The antiviral activity, pharmacokinetics and tolerability of VCH-759 administered as monotherapy for 10 days with a 14 day follow-up period were evaluated in 31 treatment-nai ve genotype 1 participants. Three cohorts received: 400mg thrice (t.i.d.), 800 mg twice (b.i.d.), 800 mg t.i.d or placebo. RESULTS: VCH-759 was well tolerated with the most frequent adverse event being gastrointestinal upset in both the active and placebo groups attributable, in part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma levels were at or above the IC(90) (non protein-adjusted) for all dosing regimens. The mean maximal decrease in HCV RNA log(10) (IU/mL) was 1.97, 2.30 and 2.46 for 400mg t.i.d., 800 mg b.i.d. and 800 mg t.i.d. doses. Viral polymerase genotypic sequencing revealed emergence of HCV variants in a majority of participants that coincided with on-treatment viral rebound. CONCLUSIONS: VCH-759 was well tolerated and achieved a> or =2 log(10) decline in HCV RNA with 800 mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was observed and associated with resistant variants. This data supports further evaluation of VCH-759 in combination with interferon-ribavirin treatment.
Authors: Dominique Larrey; Ansgar W Lohse; Christian Trepo; Jean-Pierre Bronowicki; Keikawus Arastéh; Marc Bourlière; Jose Luis Calleja; Jerry O Stern; Gerhard Nehmiz; Nasri Abdallah; Kristi L Berger; Martin Marquis; Jürgen Steffgen; George Kukolj Journal: Antimicrob Agents Chemother Date: 2013-07-15 Impact factor: 5.191
Authors: Andrew S Bae; Karin S Ku; Michael D Miller; Hongmei Mo; Evguenia S Svarovskaia Journal: J Clin Microbiol Date: 2011-06-29 Impact factor: 5.948
Authors: Hadas Dvory-Sobol; Christian Voitenleitner; Eric Mabery; Taylor Skurnac; Eric J Lawitz; John McHutchison; Evguenia S Svarovskaia; William Delaney; Michael D Miller; Hongmei Mo Journal: Antimicrob Agents Chemother Date: 2014-08-25 Impact factor: 5.191
Authors: Min Jiang; Eileen Z Zhang; Andrzej Ardzinski; Ann Tigges; Andrew Davis; James C Sullivan; Michelle Nelson; Joan Spanks; Jennifer Dorrian; Olivier Nicolas; Doug J Bartels; B Govinda Rao; Rene Rijnbrand; Tara L Kieffer Journal: Antimicrob Agents Chemother Date: 2014-06-30 Impact factor: 5.191