First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor.
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.
Academic Medical Center, Amsterdam, The Netherlands.
J
J
de Bruijne
J
J
van de Wetering de Rooij
A A
AA
van Vliet
X J
XJ
Zhou
M F
MF
Temam
J
J
Molles
J
J
Chen
K
K
Pietropaolo
J Z
JZ
Sullivan-Bólyai
D
D
Mayers
H W
HW
Reesink
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007769:Lactams / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C578225:IDX375; D007769:Lactams; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D012324:RNA-Dependent RNA Polymerase