Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study

Mauck, Christine; Weiner, Donald A.; Ballagh, Susan A.; Creinin, Mitchell D.; Archer, David F.; Schwartz, Jill L.; Pymar, Helen; Lai, Jaim Jou; Callahan, Marianne M.

doi:10.1016/s0010-7824(01)00271-2

Cited by 81 publications

(37 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that resolution of findings occurred rapidly in the presence of the products. This pattern of colposcopic findings was also seen in a previous safety study of similar design involving cellulose sulfate [18]. This was our second study to attempt to correlate subjective leakage of a vaginal product with an objective measure of it.…”

Section: Discussionsupporting

confidence: 73%

“…This was our second study to attempt to correlate subjective leakage of a vaginal product with an objective measure of it. As in the previous study [18], agreement between the objective and subjective measures of leakage was poor. This may stem from a true lack of agreement, from problems with the instruments used to obtain the data, or both.…”

Section: Discussionsupporting

confidence: 52%

See 1 more Smart Citation

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

et al. 2004

Self Cite

View full text Add to dashboard Cite

Objectives-To evaluate symptoms and signs of genital irritation, vaginal leakage and acceptability of polystyrene sulfonate (PSS), which is being studied as a vaginal contraceptive and microbicide.Methods-Forty-nine women applied 2.5 mL of either 5% PSS, 10% PSS, PSS vehicle, or Conceptrol ® (a marketed spermicidal product containing 4% nonoxynol-9) for 6 consecutive days.Results-All women completed the study except one in the Conceptrol group who experienced vaginal symptoms after her first use and was discontinued. After both the first use and after all uses, irritation was seen among more women in the Conceptrol group than in the PSS groups, reaching statistical significance with regard to any evidence of irritation, signs of irritation and product-related irritation. There were no adverse events that were serious, unexpected and related to product use in any group. The 5% concentration of PSS may be preferable in terms of leakage and acceptability. Conclusion-The results suggest that PSS has a safety profile comparable to that of the marketed nonoxynol-9 product, Conceptrol, and appears to be associated with less genital irritation.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 52%

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…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: 94%

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

Mauck

Lai

Weiner

et al. 2013

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…A 6-day study conducted on women in the United States suggested that 6% CS was as safe and acceptable as the control, K-Y Jelly [6]. Similarly, CS was found to be safe when applied to the penis for seven consecutive days [7].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

Self Cite

View full text Add to dashboard Cite

TitleFourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study Abstract Background: Topical microbicides against the human immunodeficiency virus (HIV) 1 that are nonirritating to the female genital epithelium are urgently needed to slow the heterosexual spread of HIV infection. Products that are also effective contraceptives provide additional benefits. Cellulose sulfate (CS) is a noncytotoxic antifertility agent that exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV. Methods: We performed a multicenter, Phase I, placebo-controlled, randomized study to evaluate the genital toxicity of CS. Two cohorts of healthy women used 3.5 ml of 6% CS gel or 3.5 ml of K-Y Jelly, vaginally, bid, for 14 days. The first cohort was sexually abstinent, and the second cohort was sexually active. Results: CS was associated with only a slightly higher odds ratio (OR) of symptoms of minor urogenital irritation compared to the inactive lubricant K-Y Jelly (OR = 2.02, 95% confidence interval = 0.90-4.53). In addition, there were minor shifts in some genital flora, but there was no evidence of greater inflammation as evidenced by few colposcopic findings, decreased influx of polymorphonuclear cells and minimal changes in proinflammatory cytokines. Moreover, both products appeared acceptable to most women. Product leakage was identified as more of a problem in sexually abstinent women, but less so in women using the product for sexual intercourse, as would be the case in actual practice. Conclusion: CS was safe for twice-daily use for 14 days. CS is appropriate for future studies in effectiveness trials. D

show abstract

Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study

Cited by 81 publications

References 16 publications

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

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

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

Contact Info

Product

Resources

About