Microgynon Riociguat Drug Interaction Study in Healthy Postmenopausal Women

Study Overview
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Brief Summary
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Physicians might be concerned that Adempas may have a metabolic interaction with oral contraceptives (OC) that could decrease the contraceptive efficacy of the OC. The information regarding lack of potential pharmacokinetic interaction has been communicated; there is a need for more re-assurance and further data that there is no interaction between Adempas and OCs. A drug-drug interaction study of riociguat with an OC such as Microgynon in the least vulnerable population for these purposes, i.e. healthy postmenopausal women, is considered adequate to inform about safe use of Adempas with OCs.

Official Title
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Microgynon Riociguat Drug Interaction Study to Investigate the Effect of Riociguat 2.5 mg 3 Times Daily Multiple-dose Treatment on the Plasma Concentrations of / Exposure to Levonorgestrel and Ethinyl Estradiol in Healthy Postmenopausal Women in a 2-fold Crossover Design

Conditions
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Drug Interactions

Intervention / Treatment
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* Drug: Microgynon
* Drug: Riociguat (Adempas,BAY63-2521)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female subject Non-smokers of at least 3 month before screening Age: 52 to 65 years (inclusive) at the first screening examination Ethnicity: white Body mass index (BMI)>=20 and <=32 kg/m2 Postmenopausal state, defined as Medical history, if applicable (natural menopause at least 12 months before the first study drug administration and hormone analyses in serum Age<60 years: follicle-stimulating hormone (FSH) >40 IU/L in plasma Age <60 years: estradiol (E2) <20 ng/L (<73 pmol/L) in plasma Exclusion Criteria: History of coronary artery disease, Symptomatic postural hypotension, History of bronchial asthma, known hypersensitivity to the study, relevant diseases within 4 weeks before study drug administration, Presence or a history of venous or arterial thrombotic / thromboembolic events or cerebrovascular accident, a high risk for venous or arterial thrombosis, Use of systemic or topical medicines or substances which oppose the study objectives, smoking, use of sex hormones in any forms Clinically relevant findings in the ECG, systolic blood pressure below 110 or above 145 mmHg, heart rate below 50 or above 95 beats per minute Clinically relevant findings in the gynecological examination, Participation in another clinical study

Ages Eligible for Study
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Minimum Age: 52 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1<br>single oral tablet dose of Microgynon (0.03 mg EE and 0.15 mg LNG, fasted) | Drug: Microgynon<br>* single oral tablet dose of Microgynon (0.03 mg EE and 0.15 mg LNG, fasted)<br>|
| Experimental: Arm2<br>multiple oral tablet doses of 2.5 mg riociguat TID over 12 days and, on the seventh day of this treatment, a single oral tablet dose of Microgynon (0.03 mg EE and 0.15 mg LNG, fasted) | Drug: Microgynon<br>* single oral tablet dose of Microgynon (0.03 mg EE and 0.15 mg LNG, fasted)<br>Drug: Riociguat (Adempas,BAY63-2521)<br>* multiple oral tablet doses of 2.5 mg riociguat TID over 12 days and, on the seventh day of this treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration time curve (AUC) of Ethinylestradiol (EE) | Plasma concentrations Ethinyl estradiol (EE) and levonorgestrel (LNG) | Up to 4 months | 
| Area under the plasma concentration time curve (AUC) of Levonorgestrel (LNG) |  | Up to 4 months | 
| Maximal concentration (Cmax) of Ethinylestradiol (EE) |  | Up to 4 months | 
| Maximal concentration (Cmax) of Levonorgestrel (LNG) |  | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 4 months |