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
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Clinical Trial
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Randomized Controlled Trial
MeSH terms
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Adult
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Antiviral Agents / adverse effects
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Antiviral Agents / pharmacokinetics*
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Antiviral Agents / pharmacology*
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Antiviral Agents / therapeutic use
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Enzyme Inhibitors / adverse effects
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Female
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Hepatitis C / drug therapy
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Hepatitis C / virology*
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Humans
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Lactams / adverse effects
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Lactams / pharmacokinetics*
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Lactams / pharmacology*
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Lactams / therapeutic use
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Male
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Middle Aged
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Organophosphorus Compounds / adverse effects
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Organophosphorus Compounds / pharmacokinetics*
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Organophosphorus Compounds / pharmacology*
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Organophosphorus Compounds / therapeutic use
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RNA, Viral / blood
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Viral Load / drug effects
Substances
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Antiviral Agents
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Enzyme Inhibitors
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IDX375
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Lactams
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Organophosphorus Compounds
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RNA, Viral
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RNA-Dependent RNA Polymerase