Pharmacokinetics and Safety of the Selective Progesterone Receptor Modulator Vilaprisan in Chinese Healthy Postmenopausal Women

Abstract

Vilaprisan is a novel selective progesterone receptor modulator for the long-term treatment of uterine fibroids and endometriosis. This study investigated the pharmacokinetics, safety, and tolerability of vilaprisan in healthy Chinese postmenopausal women. Twelve participants received multiple doses of vilaprisan once daily over 14 days as a 2-mg tablet. Plasma vilaprisan concentrations were determined using liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters of vilaprisan were assessed with noncompartmental analysis, including maximum observed concentration (C max ), systemic exposure (area under the plasma concentration-time curve), time to reach C max and terminal half-life. Safety assessments include the documentation of adverse events, measurement of clinical/anthropometric parameters and vital signs, electrocardiogram, and physical and gynecologic examination. The participants had a mean age of 53.3 (± 4.2) years and a body mass index of 23.8 ± 2.8 kg/m 2 . Median time to reach C max was 1.5 hours after both single and multiple vilaprisan administration. Mean C max values obtained after multiple dosing (23.3 μg/L [standard deviation (SD) = 6.73]) were 1.92-fold (SD = 0.554) higher compared to single dosing (12.5 μg/L [SD = 3.04]). Mean area under the plasma concentration-time curve in the dosing interval increased with an accumulation factor of 2.98 (SD = 0.767) between single (91.3 μg • h/L [SD = 20.4]) and multiple dosing (276 μg • h/L [SD = 109]). The mean terminal half-life of vilaprisan was 44.5 hours (SD = 10.3) after multiple dosing. Mild to moderate adverse events were observed similar to previous studies. Overall, daily oral administration of the therapeutic dose of 2 mg of vilaprisan over 14 days was safe and well tolerated by all participants.

Clinical Pharmacokinetics and Pharmacodynamics of the Selective Progesterone Receptor Modulator Vilaprisan: A Comprehensive Overview

“…All data presented in this section were collected in populations of healthy postmenopausal women, mainly Caucasians, unless otherwise stated. Vilaprisan was generally administered in the form of 2 or 5 mg immediate-release tablets, and the validated liquid chromatography-tandem mass spectrometry method described by Liu et al [10] was used to determine vilaprisan in plasma. A condensed overview of the absorption, distribution, and elimination characteristics of vilaprisan in humans is given in Fig.…”

“…No major impact of ethnicity or race on the PK of vilaprisan was detected. Furthermore, neither was 'racial category' identified as a significant covariate in the population PK analysis [23], and nor were there any major differences in vilaprisan exposure between the mainly Caucasian, Chinese, and Japanese populations studied in phase I studies of vilaprisan [10,12] (ESM 2). However, as mentioned above, the number and racial and ethnic diversity of the patients included in the phase I and II studies was limited.…”

Effect of Food Intake on the Pharmacokinetics of the Selective Progesterone Receptor Modulator Vilaprisan: A Randomized Clinical Study in Healthy Postmenopausal Women

“…To determine the concentration of vilaprisan in plasma samples, the same liquid chromatography-tandem mass spectrometry method was used as in previously published studies with vilaprisan. This method was described by Liu et al, 11 for example. An overview of the performance of the method in the present study is given in Supplement 2.…”