Abstract
BACKGROUND: Vilaprisan is a selective progesterone receptor modulator with demonstrated efficacy in the management of uterine fibroids (UFs). OBJECTIVES: To evaluate the safety and efficacy of vilaprisan in Japanese women with UFs and heavy menstrual bleeding (HMB). DESIGN: Open-label, parallel-group, Phase 3 randomized clinical trial. METHODS: Japanese women with UFs and HMB were randomly assigned 1:1 to receive vilaprisan (2 mg/day) for either four treatment periods (TPs) of 12 weeks each separated by one bleeding period (Arm A1) or two TPs of 24 weeks each separated by two bleeding periods (Arm A2). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). RESULTS: Of 179 women enrolled, 151 were included in the full analysis set and 148 in the safety analysis set. TEAEs occurred in 79.1% of women, with the majority being mild; events were evenly distributed across both treatment arms. Study drug-related TEAEs were observed in 44.6% of women, and serious TEAEs were reported in 3.4% of women. During the treatment phase, the mean (standard deviation) number of bleeding days per 28 days decreased to 1.40 (1.34) days in Arm A1 and 1.42 (0.82) days in Arm A2 from respective baseline values of 5.1 (2.3) and 5.2 (2.0) days. Median time to onset of amenorrhea was 4 days in TP1 in both arms, and 4 days in TP2 in Arm A1. Absence of bleeding for the last 28 days was more common in TP1 (Arm A1: 91.89%, Arm A2: 89.19%) than TP2 (Arm A1: 80.85%, Arm A2: 85.71%). CONCLUSION: In this study, vilaprisan 2 mg/day was found to be well tolerated and efficacious in Japanese women with UFs and HMB. However, the study sponsor later terminated the overall clinical development of vilaprisan due to potential safety concerns from long-term rodent studies. REGISTRATION: The ASTEROID 8 study was registered at https://clinicaltrials.gov/ (registration number: NCT03476928).