Drug-drug Interaction Study Between Orally Administered Rifampicin and Vilaprisan

Study Overview
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Brief Summary
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This study will be conducted in a single center, open-label study with a single group fixed sequence design to evaluate the effect of repeated oral administration of 600 mg RIF(Rifampicin) given once daily over 11 days on the single oral dose pharmacokinetics of VPR(Vilaprisan) and on MDZ(Midazolam) as a reference (probe) substance.

Official Title
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Non-randomized, Non-blinded, Non-placebo-controlled Study to Investigate the Influence of Repeated Daily Administration of 600 mg Rifampicin Given Once Daily Over 11 Days on the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of 4 mg Vilaprisan in Healthy Postmenopausal Women.

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Rifampicin
* Drug: Midazolam
* Drug: BAY1002670_Vilaprisan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female postmenopausal subjects Age: 45 to 65 years (inclusive) Body mass index (BMI) : ≥20 and ≤32 kg/m² Race: White Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Relevant diseases within the last 4 weeks prior to the first drug administration Existing chronic diseases requiring medication Known or suspected malignant tumors (including history of malignant tumors, with a status after treatment), known or suspected benign tumors of the liver and pituitary (including after treatment) Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal Regular use of medicines Repeated use of drugs during 1 week before first study drug administration which might affect absorption (e.g. laxatives, loperamide, metoclopramide, antacids, H2-receptor antagonists)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treatment A (Period 1): a single oral dose of 4 mg Vilaprisan and 1 mg Midazolam Treatment B (Period 2): 600 mg Rifampicin once daily (qd) for 7 days followed by administration of a single oral dose of 4 mg Vilaprisan and 1 mg Midazolam followed by 600 mg Rifampicin 12 hours after Vilaprisan and Midazolam administration and continued dosing of 600 mg Rifampicin once daily for 3 days | Drug: Rifampicin<br>* 11 single oral doses of 600 mg Rifampicin resulting in a total dose of 6600 mg Rifampicin.<br>Drug: Midazolam<br>* 2 single oral doses of 1 mg Midazolam resulting in a total dose of 2 mg Midazolam<br>Drug: BAY1002670_Vilaprisan<br>* 2 single oral doses of 4 mg Vilaprisan resulting in a total dose of 8 mg Vilaprisan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of Vilaprisan in plasma with co-medication Rifampicin |  | blood sampling for pharmacokinetics of Vilaprisan (LC-MS/MS) at the following time points post administration of Vilaprisan and Midazolam: 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,15 hour, thereafter daily sampling up to 14 days | 
| Cmax of Vilaprisan in plasma with co-medication Rifampicin |  | blood sampling for pharmacokinetics of Vilaprisan (LC-MS/MS) at the following time points post administration of Vilaprisan and Midazolam: 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,15 hour, thereafter daily sampling up to 14 days | 
| AUC of Vilaprisan in plasma without co-medication Rifampicin |  | blood sampling for pharmacokinetics of Vilaprisan (LC-MS/MS) at the following time points post administration of Vilaprisan and Midazolam: 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,15 hour, thereafter daily sampling up to 14 days | 
| Cmax of Vilaprisan in plasma without co-medication Rifampicin |  | blood sampling for pharmacokinetics of Vilaprisan (LC-MS/MS) at the following time points post administration of Vilaprisan and Midazolam: 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,15 hour, thereafter daily sampling up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vilaprisan, PK, rifampicin, midazolam,, CYP3A4 induction, drug-drug interaction