A phase I randomized safety study of a single-size silicone rubber diaphragm used with or without a lactic-acid-containing diaphragm gel.

OBJECTIVES: To evaluate a lactic-acid-containing diaphragm gel (Contragel®) approved outside the United States for use with a silicone rubber diaphragm (Caya®). The study gel is being evaluated as a safer alternative to nonoxynol-9 (N-9) gel, which has been associated with risk of increasing susceptibility to human immunodeficiency virus (HIV). STUDY DESIGN: This was a Phase I randomized, parallel study evaluating the safety of the novel diaphragm gel versus hydroxyethylcellulose (HEC) universal placebo gel delivered by the study diaphragm for two 7-day test cycles of daily use, without and with intercourse. The primary clinical safety endpoint was treatment emergent adverse events. Mucosal safety endpoints included colposcopic findings, anti-Escherichia coli activity of endocervical and vaginal fluid, immune mediators, Nugent score and ectocervical immune cell density. Endpoints were assessed prior to each test cycle and at day 7 of each test cycle. We compared the two independent groups and also evaluated paired changes from baseline in each gel cohort. RESULTS: Twenty-three participants used the study diaphragm with the novel gel (n=11) or with HEC (n=12). Use of either gel resulted in few genital AEs and no colposcopic findings. There were no differences in ectocervical histology and lymphocyte density or phenotype between the two cohorts at baseline or after each test cycle. We found no clinically important differences in the anti-microbial (anti Escherichia coli) activity of endocervical or vaginal fluid or concentrations of genital immune mediators (e.g. anti-inflammatory secretory leukocyte protease inhibitor (SLPI) or pro-inflammatory mediator RANTES) between the two gel cohorts at any visit. There were no important paired changes from baseline among participants using either gel in Nugent score, ectocervical histology or anti-microbial activity of genital secretions. CONCLUSIONS: We found no clinically significant differences in clinical and mucosal safety endpoints between the two cohorts. The mucosal safety profiles of the study gel and HEC placebo gel were similar. IMPLICATIONS: Our data demonstrate no clinically important differences between the safety profiles of the lactic-acid-containing diaphragm gel versus HEC placebo gel when used with the study diaphragm. N-9 can no longer be used with contraceptive diaphragms in high HIV prevalence regions. Although larger studies are needed, the novel gel appears safe for use with the study diaphragm, which is the first over-the-counter, non-hormonal, diaphragm.

A phase I randomized postcoital testing and safety study of the Caya diaphragm used with 3% Nonoxynol-9 gel, ContraGel or no gel.

OBJECTIVES: The Caya® Diaphragm is a newly approved single-size, nonlatex diaphragm. Contragel® is a personal lubricant containing lactic acid approved in Europe and other countries for use with vaginal barrier devices. This study assessed the effectiveness in preventing sperm from penetrating midcycle cervical mucus of Caya with Contragel, Caya with 3% nonoxynol-9 (N-9) and Caya alone. STUDY DESIGN: Phase I multicenter, single-blind, randomized, crossover, nonsignificant risk study at two sites: Eastern Virginia Medical School, Norfolk, VA, USA, and Profamilia, Santo Domingo, Dominican Republic. Healthy, sexually active women 18-45years old, not at risk for pregnancy due to tubal occlusion, were eligible. Each participant was seen in nine visits, completing a baseline cycle (without product use) followed by three test cycles (sequence determined by randomization), each consisting of a cervical mucus check visit and a postcoital test visit. To proceed to test cycles, the baseline postcoital test had to show adequate cervical mucus and >5 progressively motile sperm per high power field (PMS/HPF). RESULTS: All women had an average of <5 PMS/HPF during the test cycle of each study arm, the primary endpoint. Caya with ContraGel and Caya with N-9 reduced the average number of PMS/HPF from 22.5 to 0. Caya alone reduced the average number of PMS/HPF from 22.5 to 0.4. There were two possibly product-related mild adverse events. CONCLUSION: This study supports that Caya with ContraGel is safe and functions as well as Caya with N-9 in preventing PMS from reaching midcycle cervical mucus. IMPLICATIONS: A single-size diaphragm used with a personal lubricant gel containing lactic acid appears to be safe and to function as well as the same diaphragm used with N-9 in preventing PMS from reaching midcycle cervical mucus.