Nonoxynol-9 100 mg gel: multi-site safety study from sub-Saharan Africa.
OBJECTIVE
To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study.


METHODS
HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days.


RESULTS
The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively).


CONCLUSIONS
N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.
Hoffman
Irving F
IF
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA. hoffmani@med.unc.edu
Taha
Taha E
TE
Padian
Nancy S
NS
Kelly
Clifton W
CW
Welch
Julia D
JD
Martinson
Francis E
FE
Kumwenda
Newton I
NI
Rosenberg
Zeda F
ZF
Chilongozi
David A
DA
Brown
Joelle M
JM
Chirenje
Michael
M
Richardson
Barbra A
BA
D000282:Administration, Intravaginal; D000328:Adult; D003906:Developing Countries; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008295:Malawi; D009092:Mucous Membrane / Q000187:drug effects; D017137:Nonoxynol / Q000009:adverse effects* / Q000627:therapeutic use; D013089:Spermatocidal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D014456:Ulcer / Q000139:chemically induced*; D014621:Vagina; D014623:Vaginal Diseases / Q000139:chemically induced*; D015030:Zimbabwe
D005782:Gels; D013089:Spermatocidal Agents; D017137:Nonoxynol