Contraceptive efficacy of 50 mg Mifepristone once-a-week: an open label, single-arm, multicenter clinical trial in Moldova

Introduction: Unmet needs for contraception persist partly due to side effects, dissatisfaction, and medical contraindications. Mechanistic and clinical data support the contraceptive potential of mifepristone, which may provide a non-estrogen contraceptive option, but evidence remains limited. The primary aim of this trial was to evaluate the contraceptive efficacy and safety of once-weekly 50 mg mifepristone. Method: We conducted an open-label, single-arm, multicenter trial in Moldova. Women aged 18-35 years used mifepristone as their sole contraceptive method for 13 cycles. The primary endpoint was pregnancy due to method failure, expressed as a Pearl Index (PI). Results: Of 170 women enrolled between August 2023 and May 2025, 146 initiated treatment. Two pregnancies occurred during 1,187 evaluable cycles, with a perfect-use at-risk PI of 1.55 (95% CI, 0.04-8.64). Increased endometrial thickness occurred in 8.9% (11/123) of participants and progesterone receptor modulator-associated endometrial changes in 10.6% (13/123), which normalized at follow up. No hyperplasia or cellular atypia was detected in any of the endometrial biopsies. Bleeding averaged one day per cycle, and 60% reported no bleeding or spotting at treatment end. Overall, 95.6% were satisfied or very satisfied with the method. Conclusions: Due to early discontinuation of the trial the study did not achieve the planned sample size. The subsequent imprecise estimated PI did not meet the prespecified efficacy criterion. However, the favorable safety profile, bleeding pattern, and high acceptability supports continued development of mifepristone as a contraceptive.