Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics
- Conditions
- Healthy Subjects
- Interventions
- Registration Number
- NCT03389321
- Lead Sponsor
- Actelion
- Brief Summary
Both macitentan and riociguat are indicated in the treatment of pulmonary arterial hypertension (PAH) and may be administered concomitantly. The primary objective of this study is to evaluate the effect of macitentan administered for 11 days on the pharmacokinetics (PK) (i.e., amount and time of presence in the blood of riociguat) of a single dose of riociguat in healthy male subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
- Male subjects aged between 18 and 45 years (inclusive) at screening who signed informed consent prior to any study-mandated procedure;
- Healthy on the basis of physical examination, cardiac evaluations (12-lead ECG) and laboratory tests performed at screening;
- Body mass index of 18 to 30 Kg/m2 (inclusive) at screening;
- Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 beats per minute (inclusive).
Key
- Known allergic reactions or hypersensitivity to macitentan, riociguat, any drug of the same classes, or any of their excipients;
- Any contraindication for riociguat treatment;
- Known hypersensitivity or allergy to natural rubber latex;
- Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions;
- History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatments;
- Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks prior to first study treatment administration;
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Other protocol defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment A-B Macitentan (Opsumit) All subjects will receive treatment A followed by treatment B. Treatment A consists of a single oral dose (1 mg) of riociguat (Adempas) on Day 1. Treatment B consists of a loading oral dose of 30 mg macitentan (Opsumit) (3 tablets of 10 mg) on Day 5, then 10 mg of macitentan once daily from Day 6 to Day 15, with a concomitant administration of riociguat (1 mg) on Day 10. Treatment A-B Riociguat (Adempas) All subjects will receive treatment A followed by treatment B. Treatment A consists of a single oral dose (1 mg) of riociguat (Adempas) on Day 1. Treatment B consists of a loading oral dose of 30 mg macitentan (Opsumit) (3 tablets of 10 mg) on Day 5, then 10 mg of macitentan once daily from Day 6 to Day 15, with a concomitant administration of riociguat (1 mg) on Day 10.
- Primary Outcome Measures
Name Time Method Area under the plasma concentration-time curve (AUC) from zero to infinity [AUC(0-inf)] of riociguat Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) AUC(0-inf) of riociguat will be assessed following administration of riociguat alone or concomitantly with macitentan.
Maximum plasma concentration (Cmax) of riociguat Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) The maximum observed plasma concentration of riociguat will be assessed following administration of riociguat alone or concomitantly with macitentan.
- Secondary Outcome Measures
Name Time Method AUC(0-inf) of riociguat metabolite M1 Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) AUC(0-inf) of M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Time to reach Cmax (tmax) of riociguat and its metabolite M1 Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) The maximum observed time to reach Cmax of riociguat and M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Maximum plasma concentration (Cmax) of riociguat metabolite M1 Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) The maximum observed plasma concentration of M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
Elimination half life (t1/2) of riociguat and its metabolite M1 Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) t1/2 of riociguat and M1 will be assessed following administration of riociguat alone or concomitantly with macitentan.
AUC(0-t) of riociguat and its metabolite M1 Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose) AUC(0-t) is the area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification. It will be determined for both riociguat and its metabolite M1 following administration of riociguat alone or concomitantly with macitentan.
Trough concentration (Ctrough) of macitentan and its metabolite ACT-132577 Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16 Ctrough of macitentan and its metabolite ACT-132577 will be assessed during the treatment period with macitentan (Day 10 to Day 15)
Trial Locations
- Locations (1)
CRS Clinical Research Services Mannheim
🇩🇪Mannheim, Germany