A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor

Sex Transm Dis. 2008 Apr;35(4):414-9. doi: 10.1097/OLQ.0b013e318162c4d8.

Abstract

Goal: This study evaluated the effect of a single dose and 5 additional consecutive daily doses of UC781 gel at concentrations of 0.1%, 0.25%, 1.0%, and 0% on urogenital irritation.

Study design: Forty-eight healthy sexually abstinent women were randomly assigned to 1 of 4 groups.

Methods: Urogenital irritation was assessed by pelvic examination, colposcopy, and reports of genital symptoms at baseline and after 1 and 6 doses. Vaginal health was assessed by wet mount and systemic safety by laboratory evaluation after 1 and 6 doses, and UC781 levels were assessed at baseline and after 6 doses.

Results: Some evidence of urogenital irritation was common in all treatment groups and was most often transient and mild. Colposcopic findings were infrequent in the placebo group (8%) and more common in the 3 treatment groups (24%-42%). Edema, which may indicate underlying inflammation, was observed in the vaginal fornix of 2 women exposed to UC781. There was no apparent increase in vaginal infection or clinically significant changes in laboratory values. Two of 12 participants randomized to 1% UC781 gel had detectable plasma levels that were less than the lower level of quantification.

Conclusions: UC781 was well tolerated in this initial dose ranging safety study when used once daily for 6 days in sexually abstinent women. Five safety/pharmacokinetic studies of UC781 are currently underway in women and men, all utilizing UC781 concentrations less than 1%, with twice-daily dosing in some studies, and all involving careful monitoring of exposed epithelium.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Adult
  • Anilides / administration & dosage*
  • Anilides / adverse effects
  • Colposcopy
  • Female
  • Furans / administration & dosage*
  • Furans / adverse effects
  • HIV Infections
  • Humans
  • Middle Aged
  • Patient Satisfaction
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / adverse effects
  • Thioamides
  • Treatment Outcome
  • Urogenital System / drug effects*
  • Vaginal Creams, Foams, and Jellies / administration & dosage

Substances

  • Anilides
  • Furans
  • Reverse Transcriptase Inhibitors
  • Thioamides
  • Vaginal Creams, Foams, and Jellies
  • UC-781