Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women

Schultze‐Mosgau, Marcus‐Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank S.; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

doi:10.5414/cp202756

Cited by 24 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maximum plasma concentrations and systemic exposure to VPR increased dose proportionally in the dose range of 0.5 to 4 mg. The pharmacokinetic data obtained in this study were in the range of values observed in prior studies with VPR and confirmed that treatment compliance was good.…”

Section: Resultssupporting

confidence: 84%

See 1 more Smart Citation

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

Schütt

Schultze‐Mosgau

Draeger

et al. 2017

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 84%

“…No new safety signals were detected. The adverse events observed in this study confirmed the known safety profile of VPR as determined in previous clinical studies . No treatment‐emergent serious adverse events occurred in this study.…”

Section: Discussionsupporting

confidence: 88%

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

Schütt

Schultze‐Mosgau

Draeger

et al. 2017

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, as expected, no relevant differences in the pharmacokinetics were seen between male and female subjects. Although vilaprisan is intended to be used for long‐term treatment, investigating a single dose of 2 mg in this study was justified considering that vilaprisan shows linear pharmacokinetics upon multiple dosing, thereby allowing us to extrapolate these results to a multiple dosing scenario …”

Section: Discussionmentioning

confidence: 58%

“…The expected vilaprisan exposure at steady state for participants with moderate hepatic impairment, given the anticipated accumulation due to the apparent slight prolongation of the terminal elimination half‐life, is within the ranges included in a previous multiple‐dose study . In this previously conducted study, no safety concerns were identified with vilaprisan at doses up to 30 mg day −1 over 28 days . No safety concerns are expected upon multiple daily dosing in patients with mild or moderate hepatic impairment, based on these pharmacokinetic observations.…”

Section: Discussionmentioning

confidence: 85%

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

Chattopadhyay

Riecke

Ligges

et al. 2019

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims The study objective was to evaluate the pharmacokinetics of the selective progesterone receptor modulator vilaprisan in participants with hepatic impairment. Additionally, the safety and tolerability of vilaprisan were investigated. Methods In this phase 1, open‐label, nonrandomised, parallel‐group, pharmacokinetic study, men and women with mild or moderate hepatic impairment (Child–Pugh grade A or B) and control participants with normal hepatic function matched by age, weight and sex received a single oral 2 mg dose of vilaprisan. Key pharmacokinetic parameters, relationships between parameters and safety outcomes were measured. Results Thirty‐six participants completed the study: 9 with mild hepatic impairment, 9 with moderate hepatic impairment and 18 matched control participants with normal hepatic function. Vilaprisan reached maximum plasma concentrations after 1–2 hours. Unbound vilaprisan exposure was 1.44‐fold higher for participants with mild hepatic impairment vs controls (90% confidence interval: 0.91–2.26), and 1.74‐fold higher for participants with moderate impairment vs controls (90% confidence interval: 1.09–2.78). The maximum observed unbound peak concentrations were similar for participants with hepatic impairment and matched controls. Vilaprisan 2 mg was well tolerated and the incidence of treatment‐emergent adverse events was similar across cohorts. Conclusion Only mild increases of <1.75‐fold in exposure were observed in participants with mild or moderate hepatic impairment compared with control participants. No safety concern was identified. These data, alongside the excellent safety profile observed in phase 1 and 2 studies, do not indicate that a dose adjustment would be required in patients with mild or moderate hepatic impairment.

show abstract

“…The pharmacokinetic (PK) properties of VPR have been well characterized, as described by Schultze‐Mosgau et al . . The dominant compound in the plasma after oral administration of the drug is unchanged VPR.…”

Section: Introductionmentioning

confidence: 99%

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

Chattopadhyay

Kanacher

Casjens

et al. 2018

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women

Abstract: Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range. .

Cited by 24 publications

References 0 publications

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

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

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

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

Contact Info

Product

Resources

About

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women

Abstract: Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range. .

Cited by 24 publications

References 0 publications

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

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

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

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

Contact Info

Product

Resources

About

Abstract: Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range. .