Expanded Phase I safety and acceptability study of 6% cellulose sulfate vaginal gel
ABSTRACT An expanded Phase I trial was performed to assess the safety and acceptability of 6% cellulose sulfate gel (CS) in comparison with K-Y Jelly.
Sexually abstinent (cohort I) and sexually active (cohort II) women in India, Nigeria and Uganda applied 3.5 ml of either 6% CS gel or K-Y Jelly for seven consecutive days. Safety was assessed by symptoms and signs (including colposcopy) of genital irritation, review of adverse events, and by changes in vaginal health as assessed by microscopy.
One hundred and eighty women (90 on CS and 90 on K-Y Jelly) were enrolled. Baseline characteristics of women in both gel groups were similar. In cohort I, six (14%) women on CS and 12 (27%) on K-Y Jelly reported genital symptoms, two (in K-Y Jelly group) of whom withdrew from the study. New colposcopy findings or findings showing deterioration were detected in four (9%) women on CS and nine (21%) women on K-Y Jelly in cohort I. Two women on CS and three on K-Y Jelly in cohort II reported genital symptoms. Five women (11%) in each gel group in cohort II had new colposcopy findings or findings showing deterioration. The differences between the gel groups were not statistically significant. The majority of women had no problem with their assigned product.
A vaginal application of 6% cellulose sulfate twice daily for seven consecutive days is as safe and well tolerated as a similar regimen of K-Y Jelly. Further development of 6% CS for prevention of HIV and pregnancy is recommended.
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ABSTRACT: Worldwide, HIV disproportionately affects women who are often unable to negotiate traditional HIV preventive strategies such as condoms. In the absence of an effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated alternative. Topical microbicides have been investigated as one such option. The first generation topical microbicides were non-specific, broad-spectrum antimicrobial agents, including surfactants, polyanions, and acid buffering gels, that generally exhibited contraceptive properties. After extensive clinical study, none prevented HIV infection, and their development was abandoned. Second generation topical microbicides include agents with selective mechanisms of antiviral activity. Most are currently being used for, or have previously been explored as, drugs for treatment of HIV. The most advanced of these is tenofovir 1% gel: the first topical agent shown to significantly reduce HIV infection by 39% compared to placebo. This review summarizes the evolution of topical microbicides for HIV chemoprophylaxis, highlights important concepts learned, and offers current and future considerations for this area of research.The Journal of Clinical Pharmacology 06/2014; 54(6). DOI:10.1002/jcph.292 · 2.47 Impact Factor
European Neuropsychopharmacology 08/2010; 20. DOI:10.1016/S0924-977X(10)70662-3 · 5.40 Impact Factor
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ABSTRACT: Background Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. Methods In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Results Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3+ and CD45+ cells increased in biopsies after CS use. Increases in IL-8, IL-1, IL-1RA and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have higher prevalence of intermediate Nugent score, E. coli and Enterococcus and fewer Gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. Conclusions While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45+ and CD3+ cells and subclinical microflora shifts were associated with CS use and may better predict clinical failure of non-surfactant microbicides.AIDS research and human retroviruses 07/2013; DOI:10.1089/AID.2012.0345 · 2.18 Impact Factor