Effect of the Novel Selective Progesterone Receptor Modulator Vilaprisan on Ovarian Activity in Healthy Women

Abstract

This randomized, double‐blind, parallel‐group study in healthy young women investigated the effect of treatment with vilaprisan (0.5, 1, 2, or 4 mg/day for 12 weeks) on ovarian function by assessing the Hoogland score, which is based on the size of follicle‐like structures as determined by transvaginal ultrasound and on estradiol and progesterone serum concentrations. Ovulation inhibition (ie, Hoogland score <6 in treatment weeks 1‐4 and 8‐12) was observed in >80% of the subjects receiving vilaprisan ≥1 mg/day. The effect was dose dependent. With a Bayesian approach, the percentage of subjects with ovulation inhibition was estimated to increase from 37% in subjects receiving 0.5 mg/day vilaprisan to 76%, 86%, and 88% in subjects receiving 1, 2, and 4 mg/day, respectively. Follicle growth was not suppressed during treatment. The majority of subjects receiving ≥1 mg/day had a Hoogland score of 4 (active follicle‐like structures, ie, follicle diameter >13 mm, estradiol >27.2 pg/mL, no progesterone increase) both at beginning and end of treatment. Mean average estradiol as well as mean maximum progesterone concentrations were noticeably decreased during treatment with vilaprisan ≥1 mg/day compared to pretreatment, but estradiol concentrations remained >80 pg/mL. Both hormones returned to pretreatment levels after the end of treatment, indicating a rapid resumption of normal ovarian activity. Amenorrhea occurred in the majority of subjects during treatment at dosages ≥1 mg/day. The adverse events observed in this study confirm the known safety profile of vilaprisan. All in all, the results of this study support the development of vilaprisan for the long‐term treatment of uterine fibroids.

Effect of hepatic impairment on the pharmacokinetics of vilaprisan: An open‐label, single‐dose, parallel‐group study

“…Safety findings in this study were comparable with observations from previous phase 1 and phase 2 studies in which vilaprisan was well tolerated, with no drug‐related serious AEs even at the maximal daily doses used in females . Here, the most frequently observed TEAEs were headache and nausea, which were also among the most common drug‐related AEs reported alongside ovarian and cervical cyst (identified at ultrasound), fatigue, abdominal or pelvic pain, other gastrointestinal disorders (flatulence, constipation), hot flushes, and dizziness in previous studies …”

CYP3A4‐mediated effects of rifampicin on the pharmacokinetics of vilaprisan and its UGT1A1‐mediated effects on bilirubin glucuronidation in humans

“…Vilaprisan (VPR) is a selective progesterone receptor modulator (SPRM) [4][5][6][7], which is currently being tested in phase III clinical trials for the long-term treatment of patients with uterine fibroids. The pharmacokinetic (PK) properties of VPR have been well characterized, as described by Schultze-Mosgau et al [8,9].…”

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies

“…This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Phase I clinical trials (Schütt et al 2016(Schütt et al , 2018 Vilaprisan 0.5-5 mg/day for 12 weeks 1. Maximal non-bleeding rates achieved at dose of 2 mg or higher per day.…”