The effects of vilaprisan on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive-A randomized controlled trial

Aims The primary objective was to explore whether the suppression of ovarian activity induced by a combined oral contraceptive (COC) is influenced by the simultaneous intake of the selective progesterone receptor modulator (SPRM) vilaprisan (VPR). Methods In this exploratory randomized, double-blind, parallel-group study, 71 healthy premenopausal women were randomized (1:1) to receive either 2 mg/d VPR or placebo for 3 months. Concomitantly, a COC (0.15 mg levonorgestrel, 0.03 mg ethinyloestradiol) was administered in a cyclic regimen. Ovarian activity (Hoogland score based on follicle size and hormone concentrations), cervical function (Insler score), bleeding pattern and endometrial thickness/histology were assessed before treatment, in treatment cycle 3 and during follow-up. Results The known COC-driven suppression of ovarian activity was mildly affected by VPR. COC+VPR group: 22, 0 and 6% of the subjects had Hoogland scores of 4 (active follicle-like structures), 5 or 6 (ovulation). COC+placebo group: 14% of the subjects had a score of 4 and none a score of 5 or 6 (Bayesian analysis for Hoogland score = 4, median difference in response rate: 7.5%; 90% credible interval [-8.5; 23.5%]). COC effects on cervical function were moderately affected (mucus more sperm permeable under COC+VPR). COC withdrawal bleeding, in contrast, was absent in 81% of the subjects receiving COC+VPRvs0% receiving COC+placebo. Conclusion The SPRM VPR interfered with the pharmacodynamic effects of the COC. Therefore, full contraceptive effectiveness cannot be assumed without final judgement by a Pearl index study. Women on SPRMs should be advised to use nonhormonal contraception methods.