Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study

Schwartz, Jill L.; Mauck, Christine; Lai, Jaim Jou; Creinin, Mitchell D.; Brache, Vivian; Ballagh, Susan A.; Weiner, Donald A.; Hillier, Sharon L.; Fichorova, Raina N.; Callahan, Marianne M.

doi:10.1016/j.contraception.2006.02.008

Cited by 82 publications

(60 citation statements)

References 17 publications

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“…12 In the present study, CS use was associated with increases in E. coli and Enterococcus. The reduction of SLPI and MPO after CS use may explain the relative overgrowth of E. coli and Enterococcus.…”

Section: Vaginal Safety Of Cs Hec Placebo and N-9mentioning

confidence: 70%

“…12 However, CS was associated with a decrease in the protective factor SLPI, a parameter not assessed in earlier CS studies. A similar effect was seen in early trials of other microbicide candidates later found in Phase III trials not to be effective.…”

Section: Vaginal Safety Of Cs Hec Placebo and N-9mentioning

confidence: 94%

“…1 Several microbicide candidates looked promising during preclinical evaluation but failed in efficacy trials: nonoxynol-9 (N-9), [2][3][4][5][6][7] Carraguard, 8 BufferGel, 9 PRO 2000, 10 and cellulose sulfate (CS). [11][12][13][14][15][16][17][18][19] CS did not prevent, and, when frequently used, may have increased the risk of HIV acquisition. 20,21 N-9, also when used frequently, raised the risk of HIV infection.…”

mentioning

confidence: 99%

“…12 Vaginal biopsies and endocervical cytobrush specimens were obtained at Visits 2 (baseline) and 5 as previously described. 25 Adverse events were assessed throughout follow-up.…”

mentioning

confidence: 99%

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Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure

Mauck

Lai

Weiner

et al. 2013

AIDS Research and Human Retroviruses

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TitleToward early safety alert endpoints: exploring biomarkers suggestive of microbicide failure. 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. 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. 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 interleukin (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 a higher prevalence of intermediate Nugent score, Escherichia 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. 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 help to explain the clinical failure of nonsurfactant microbicides.

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Section: Vaginal Safety Of Cs Hec Placebo and N-9mentioning

confidence: 70%

Section: Vaginal Safety Of Cs Hec Placebo and N-9mentioning

confidence: 94%

mentioning

confidence: 99%

“…12 Vaginal biopsies and endocervical cytobrush specimens were obtained at Visits 2 (baseline) and 5 as previously described. 25 Adverse events were assessed throughout follow-up.…”

mentioning

confidence: 99%

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Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure

Mauck

Lai

Weiner

et al. 2013

AIDS Research and Human Retroviruses

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“…In another CS gel study, 44% of the women in the sexually abstinent group and 18% in the CS sexually active group reported that leakage would prevent them from using the gel in the future (101). In a separate study, the author noted that reformulating the gel to reduce leakage could lead to increased irritation (102).…”

Section: Semisolids-hydrogelsmentioning

confidence: 99%

Vaginal Drug Delivery Systems for HIV Prevention

Rohan

Sassi

2009

AAPS J

140

130

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Abstract. Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.

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Topical microbicides and HIV prevention in the female genital tract

Cottrell

Kashuba

2014

The Journal of Clinical Pharma

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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.

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Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study

Cited by 82 publications

References 17 publications

Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure

Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure

Vaginal Drug Delivery Systems for HIV Prevention

Topical microbicides and HIV prevention in the female genital tract

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