Healthy Subjects
Conditions
Keywords
pharmacokinetics, macitentan, riociguat
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.
Interventions
Riociguat film-coated tablets for oral administration at a strength of 1 mg
DRUGMacitentan (Opsumit)
Macitentan film-coated tablets for oral administration at a strength of 10 mg
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
All the subjects included in the study will be included in a single group and will receive the drugs according to the same sequence
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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) |
| 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. |
Countries
Germany
Outcome results
None listed