The search for a candidate vaginal gel: an imaging trial of the distribution of four topical gel formulations in the human vagina

Abstract

There is urgent need for a vaginal microbicide, a product that women can self-administer and use to protect themselves against sexually transmitted diseases or undesired pregnancies. Recently some microbicides have failed to demonstrate clinical efficacy in phase II trials. Reasons for failure are unknown, but may include distribution of product. We compared distribution and acceptability of four different gel formulations to be used as a vehicle for a microbicide (nonionic gels [Gels A and B], and anionic gels [Gels B and C]). Randomized, double-blind comparative study. Six women inserted each of the four gels at two different time points and had a series of MRI scans taken. MRI scans were taken 10–15 minutes following intravaginal gel insertion and, at a separate visit, 4 hours following gel insertion. At each time point, scans were taken before and after simulated intercourse. All MRI scans were batch-read by a single radiologist blinded to gel allocation. Subjects reported gel leakage and other adverse events. Statistical analysis was performed using the Wilcoxon-signed-rank test for testing the continuous outcomes and the McNemar test for testing the discrete outcomes. Vaginal surface contact immediately after insertion ranged from 68% for Gel B to 92% for Gel A. Simulated intercourse increased surface contact for all gels (range 90%; Gel B: to 106%; Gel A). After four hours, surface contact was high for all four gels, (range 86% for Gel C to 102% for Gel D). Simulated intercourse at that time resulted in slightly decreased coverage for Gels C and D, and slightly increased coverage for Gels A and B (range 82% for Gel C to 99% for Gel A). All gels were noted to have some leakage within four hours of use with Gel D having the most leakage. One subject experienced mild itching/burning on two occasions using Gel D. Gel A had consistent excellent coverage of the vagina both immediately and four hours after insertion, increased coverage with simulated intercourse at both time points and the lowest standard deviation of disruption at all time points. MRI used in combination with qualitative assessments of acceptability, including leakage and adverse events, can be used to select optimal gels to be used as vehicles for potential spermicides or microbicides. We conclude that the optimal gel tested was a nonionic gel, Gel A consisting of 3% HPMC and 1.5% of Methyl Cellulose.