Vaginal ring delivery of selective progesterone receptor modulators for contraception

Abstract

Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) is under development to address the limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing and therefore might improve the effectiveness of contraception. The principal contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate (UPA) is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1 and 2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6-7 ng/mL.

Fig. 1

Design of a prototype contraceptive vaginal ring (CVR) releasing ulipristal acetate (UPA). a. Vaginal ring dimensions. b. Cross-sectional view of the CVR. The outer area contains UPA in a silicone matrix, and the inner core is an inert silicone core. [International patent application number PCT/US2005/024474 to Sitruk-Ware and Tsong, for “Sustained Release Compositions Containing Progesterone Receptor Modulators” filed July 8, 2005]

Fig. 2

Mean UPA levels at each site during the 12 weeks of treatment. Reproduced from Brache et al, 2012 [21] by permission.