Phase I clinical trial of repeat dose terameprocol vaginal ointment in healthy female volunteers.
OBJECTIVE
This safety study of terameprocol (also called M4N, EM-1421) daily vaginal application in healthy women explores its potential application as a microbicide in interrupting human immunodeficiency virus sexual transmission and additional interruption of human papillomavirus and herpes simplex virus transmission.


METHODS
A double-blind placebo controlled phase I repeat dose tolerability and pharmacokinetic, crossover study of 90 mg terameprocol (2% w/w ointment) administered intravaginally for 7 consecutive days in healthy female subjects. The pharmacokinetics after administration was examined on days 1 and 7 of dosing. Subjects underwent vaginal examination following the 6-hour pharmacokinetic sample on day 7 of each study period.


RESULTS
Recruitment started January 2006 and ended May 2006, and 14 subjects completed the study. Median age was 24 years. No treatment-related serious adverse events were reported, and there were a total of 17 treatment-emergent adverse events (AE) reported by 11 participants. The most common AE was headache. Terameprocol was not detectable in serum in pharmacokinetic samples.


CONCLUSIONS
Terameprocol was well tolerated at a 90 mg dose (2% wt/wt) administered vaginally daily for 7 days. No serious adverse events occurred and any AEs were mild. The excellent safety profile supports future clinical trial to evaluate the application of intravaginal terameprocol in women.
Khanna
Niharika
N
Department of Family and Community Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. nkhanna@umaryland.edu
Dalby
Richard
R
Connor
Alyson
A
Church
Ann
A
Stern
Jennifer
J
Frazer
Neil
N
D000282:Administration, Intravaginal; D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009637:Masoprocol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009824:Ointments; D011817:Rabbits; D015229:Sexually Transmitted Diseases, Viral / Q000517:prevention & control; D016896:Treatment Outcome; D014621:Vagina / Q000737:chemistry
D000998:Antiviral Agents; D009824:Ointments; C076852:terameprocol; D009637:Masoprocol