The distribution of a 3.5 mL (1.0%) C31G vaginal gel (SAVVY) using magnetic resonence imaging

Abstract

Objective: The objective of this study was to evaluate the distribution and retention of a 1.0% concentration (3.5ml) of Savvy vaginal gel in the human pelvis using Magnetic Resonance Imaging (MRI). Design: Open label phase I clinical trial Materials and Methods: Savvy was mixed with gadolinium at a concentration of 100:1. The mixture was placed in standard vaginal applicators to be self inserted in a normal clinical fashion. Six eligible subjects underwent a series of MRI scans. Baseline MRI was performed before insertion of the gel. MRI was performed, on separate visits, before and immediately after simulated intercourse with a synthetic phallic device within the first hour of insertion, 6 hours after insertion, and 24 hours after insertion of the gel. Results: Delivery of 3.5 ml of Savvy in the upper vagina with a standard applicator was easily accomplished and well tolerated. Coverage at 18 minutes was excellent with 92% linear coverage of the vagina and 75% surface contact coverage. The upper vagina was almost completely covered and gel was also noted in the lower vagina. Simulated intercourse after application of the gel resulted in relatively little change in overall distribution. There was a minimal increase in coverage, especially in the lateral aspects of the vagina. Simulated intercourse resulted in a decrease in the size and number of bare spots. Coverage six hours after application was substantially decreased from that of one hour. Overall coverage was approximately 60% of maximal linear coverage and 41% of surface contact. Simulated intercourse had little effect on distribution at these time periods. There was modest little coverage of the vaginal mucosa noted 24 hours after insertion. Gel covered the external os in all subjects after initial insertion at 18 minutes. Only half of the subjects had gel at the external cervical os 6 hours after administration. There was no coverage at the external os at 24 hours. Gel was noted in the endocervical canal in 4/6 subjects. The prevalence of gel in the endocervical canal was not increased after simulated intercourse. Gel was not visualized in the uterus at any time point. The applicator delivered the desired amount of gel. All women noted leakage of the product within one hour of insertion. There were few complaints of undesired symptoms and no serious adverse events. Conclusion: Savvy provided nearly complete coverage of the vaginal mucosa within one hour of insertion. Coverage was not greatly altered by simulated intercourse. Coverage diminished at 6 hours and 24 hours. Repeat administration may be necessary for coverage of this promising microbicide if it is not used with in the first few hours of application.