First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor

Antimicrob Agents Chemother. 2012 Aug;56(8):4525-8. doi: 10.1128/AAC.00451-12. Epub 2012 Jun 4.

Abstract

IDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy volunteers, as well as its antiviral activity in HCV-infected patients. IDX375, as a choline salt, was administered for 1 day to 40 healthy male volunteers (25- to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID] dose) and three patients chronically infected with HCV genotype 1 (200 mg BID only). IDX375 was well absorbed and well tolerated by all of the study participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV activity with maximal 0.5 to 1.1 log(10) reductions in plasma HCV RNA. These observations support further clinical investigations of IDX375.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy
  • Hepatitis C / virology*
  • Humans
  • Lactams / adverse effects
  • Lactams / pharmacokinetics*
  • Lactams / pharmacology*
  • Lactams / therapeutic use
  • Male
  • Middle Aged
  • Organophosphorus Compounds / adverse effects
  • Organophosphorus Compounds / pharmacokinetics*
  • Organophosphorus Compounds / pharmacology*
  • Organophosphorus Compounds / therapeutic use
  • RNA, Viral / blood
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • IDX375
  • Lactams
  • Organophosphorus Compounds
  • RNA, Viral
  • RNA-Dependent RNA Polymerase