Dose-ranging phase 1 study of TMC120, a promising vaginal microbicide, in HIV-negative and HIV-positive female volunteers.
OBJECTIVE
To evaluate the short-term safety, tolerability, and systemic exposure of a vaginal microbicide gel containing the nonnucleoside reverse transcriptase inhibitor TMC120.


METHODS
Randomized, controlled, double-blind, phase 1 trial of a gel containing 3 different concentrations of TMC120 versus placebo.


METHODS
Of the 48 HIV-negative and 16 HIV-positive women enrolled, 52 women received active product. Participants applied the gel twice daily for 7 days and were assessed on 6 occasions. Colposcopic evaluation was performed before and after first gel application and on day 8. Laboratory safety assessments were carried out on all visits except day 7. Plasma levels of TMC120 were measured on days 1 and 7.


RESULTS
All TMC120 concentrations were well tolerated, and there were no apparent differences in safety parameters. Four women (6%) had treatment-emergent mild cervical findings (petechiae in 3 women and erythema in 1 woman) of <5 mm. Plasma levels of TMC120 were quantifiable on day 1 in 7 (13%) participants and on day 7 in 39 (75%) participants using TMC120 gel.


CONCLUSIONS
The TMC120 vaginal gel was well-tolerated in this short study by HIV-negative and HIV-positive women. The implications of the absorption of TMC120 should be studied further in expanded safety and effectiveness trials.
Jespers
Vicky A
VA
Institute of Tropical Medicine, Antwerp, Belgium. vjespers@itg.be
Van Roey
Jens M
JM
Beets
Greet I
GI
Buvé
Anne M
AM
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology; D003127:Colposcopy; D004311:Double-Blind Method; D004890:Erythema / Q000139:chemically induced; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D011693:Purpura / Q000139:chemically induced; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014622:Vaginal Creams, Foams, and Jellies
D019380:Anti-HIV Agents; D011743:Pyrimidines; D014622:Vaginal Creams, Foams, and Jellies; C481671:Dapivirine