A dose-ranging phase I study of dextrin sulphate, a vaginal microbicide, in HIV-negative and HIV-positive female volunteers.
METHODS
This phase I dose-ranging study of 2 weeks of twice-daily dextrin sulphate (DS), a sulphated polymer with in vitro activity against HIV, was designed in 2 parts. Part A was a randomized, placebo-controlled, double-blind, 3-arm trial (DS4%, DS1%, placebo) in HIV-negative women. In part B, HIV-positive women received DS4% and HIV-negative women were randomized to DS4% or no gel.


RESULTS
One hundred women were enrolled from 2 sites (London and Antwerp): DS4% (n = 50, 20 of whom were HIV-positive), DS1% (n = 20), placebo (n = 10) and no gel (n = 20). There were no withdrawals related to adverse events and no cases of epithelial disruption. Spotting was reported by 24 women and numbers were significantly higher in all the gel groups (23 of 80), including placebo, compared with no gel (one of 20) (Fisher exact test P = 0.037). There was no evidence of a dose effect. Safety tests showed no evidence of systemic absorption.


CONCLUSIONS
Although there was no clear explanation for the spotting, DS4% was well tolerated. It was decided to proceed with DS4% in an expanded safety study in Africa but to restrict entry to low-risk HIV-negative women, include a no-gel group, and monitor intermenstrual bleeding closely.
McCormack
Sheena
S
Medical Research Council Clinical Trials Unit, London, UK. smccormack@ctu.mrc.ac.uk
Jespers
Vicky
V
Low-Beer
Naomi
N
Gabe
Rhian
R
Kaganson
Nicola
N
Chapman
Alan
A
Nunn
Andrew
A
Lacey
Charles
C
Van Damme
Lut
L
D000282:Administration, Intravaginal; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007560:Cote d'Ivoire; D003912:Dextrins / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects; D006678:HIV; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D012725:Sexual Behavior; D016896:Treatment Outcome; D014454:Uganda
D000890:Anti-Infective Agents; D003912:Dextrins; D005782:Gels; C091377:dextrin 2-sulfate