Clinical trial NCT03389321: Clinical Study to Investigate Effect of Macitentan on Riociguat Pharmacokinetics
Official title: A Single-center, Open-label, One-sequence, Two-treatment Study to Investigate the Effect of Macitentan at Steady State on the Pharmacokinetics of Riociguat in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: pharmacokinetics
macitentan
riociguat
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2018-01-03
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: OTHER

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.


Eligibility 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 exclusion criteria may apply.

Primary outcomes:
measure: Area under the plasma concentration-time curve (AUC) from zero to infinity [AUC(0-inf)] of riociguat
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: Maximum plasma concentration (Cmax) of riociguat
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
Secondary outcomes:
measure: Time to reach Cmax (tmax) of riociguat and its metabolite M1
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: Elimination half life (t1/2) of riociguat and its metabolite M1
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: AUC(0-t) of riociguat and its metabolite M1
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: AUC(0-inf) of riociguat metabolite M1
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: Maximum plasma concentration (Cmax) of riociguat metabolite M1
timeFrame: Day 1 (pre-dose to 96 hours post-dose ), Day 10 (pre-dose to 144 hours post-dose)
measure: Trough concentration (Ctrough) of macitentan and its metabolite ACT-132577
timeFrame: Day 10 to Day 15 (before macitentan administration) and in the morning of Day 16
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim
Study officials:
affiliation: Actelion
name: Shirin Bruderer, PhD
role: STUDY_DIRECTOR
References: