Microgynon Riociguat Drug Interaction Study in Healthy Postmenopausal Women

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

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.

Study Overview

• Status: Completed
• Conditions: Drug Interactions
• Intervention / Treatment: Drug: Microgynon; Drug: Riociguat (Adempas,BAY63-2521)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Mönchengladbach, Nordrhein-Westfalen, Germany, 41061

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 52 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Up to 4 months

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 6, 2014
• First Posted (Estimate): June 9, 2014

Study Record Updates

• Last Update Posted (Estimate): August 14, 2015
• Last Update Submitted That Met QC Criteria: August 13, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Enzyme Activators; Contraceptives, Postcoital, Hormonal; Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination; Riociguat
• Other Study ID Numbers: 17309; 2014-000829-20 (EudraCT Number)