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


METHODS
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.
Schwartz
Jill L
JL
CONRAD, Eastern Virginia Medical School, Arlington, Virginia 22209, USA. jschwartz@conrad.org
Kovalevsky
George
G
Lai
Jaim-Jou
JJ
Ballagh
Susan A
SA
McCormick
Timothy
T
Douville
Karen
K
Mauck
Christine K
CK
Callahan
Marianne M
MM
D000282:Administration, Intravaginal; D000328:Adult; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D003127:Colposcopy; D005260:Female; D005663:Furans / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections; D006801:Humans; D008875:Middle Aged; D017060:Patient Satisfaction; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013854:Thioamides; D016896:Treatment Outcome; D014566:Urogenital System / Q000187:drug effects*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage
D000813:Anilides; D005663:Furans; D018894:Reverse Transcriptase Inhibitors; D013854:Thioamides; D014622:Vaginal Creams, Foams, and Jellies; C100668:UC-781