Clinical trial NCT04211272: A 2-part Study to Investigate the Effect of Macitentan in Healthy Male Participants
Official title: A Single-center, Open-label, Single-sequence, 2-part Study to Investigate the Effect of 75 mg Macitentan Once Daily at Steady State on the Pharmacokinetics of Riociguat, Sildenafil, Rosuvastatin and Tadalafil in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2019-12-26
Enrollment: 47
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the effect of macitentan at steady state on the pharmacokinetic (PK) of a single dose of riociguat and sildenafil (Part A); and rosuvastatin (Part B) when co-administered to healthy male participants under fasted conditions.


Eligibility criteria: Inclusion Criteria:

* Male (according to their reproductive organs and functions assigned by chromosomal complement)
* Healthy on the basis of physical examination, medical history, and 12 lead electrocardiogram (ECG) performed at screening. This determination must be recorded in the participant's source documents and initialed by the investigator
* Body mass index (BMI; weight per height\^2) between 18.0 and 30.0 kilogram (kg)/meter square (m\^2) (inclusive), and body weight not less than 50.0 kg at screening and on Day -5
* Blood pressure (after the participant is supine for 5 minutes) between 100 and 140 millimeters of mercury (mmHg) systolic blood pressure (SBP), inclusive, and between 60 and 90 mmHg Diastolic blood pressure (DBP), inclusive, at screening and on Day -5. If blood pressure is out of range, up to 2 repeated assessments are permitted
* Heart rate between 45 and 90 beats per minute (bpm, inclusive) at screening and on Day -5

Exclusion Criteria:

* History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
* Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) within 14 days before the first dose of the study drug is scheduled until completion of the study
* A participant who has been on a known cytochrome P450 (CYP) inhibitor or inducer or transport inhibitor or inducer should be excluded from the study based upon the duration of the inhibitor or inductive effect and also at least 5 terminal half-lives of the drug, vitamin or herbal supplements
* Orthostatic hypotension (greater than \[\>\] 20 mmHg decrease in SBP or \>10 mmHg decrease in DBP after 2 minutes of standing compared to supine blood pressure)
* One or more of the following lab abnormalities at screening, defined as grade 1 or more by the World Health Organisation (WHO) Toxicity Grading Scale for Determining the Severity of Adverse Events, February 2003: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to (\>=) 1.25 \* upper limit of normal (ULN), total bilirubin \>=1.25 \* ULN, and Hemoglobin less than or equal to (\<=) 10.5 gram per deciliter (g/dL)

Primary outcomes:
measure: Part A and Part B: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Sildenafil, Riociguat, Rosuvastatin
timeFrame: Up to 25 days
measure: Part A and Part B: Maximum Observed Plasma Analyte Concentration (Cmax) of Sildenafil, Riociguat, Rosuvastatin
timeFrame: Up to 25 days
Secondary outcomes:
measure: Part A: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Desmethyl-sildenafil, M1 (Metabolite of Riociguat) and ACT-132577 (Metabolite of Macitentan)
timeFrame: Up to 25 days
measure: Part A: Maximum Observed Plasma Analyte Concentration (Cmax) of Desmethyl-sildenafil, M1 and ACT-132577
timeFrame: Up to 25 days
measure: Part A and Part B: Area Under the Plasma Analyte Concentration-time Curve from 0 to Time t of the Last Measured Concentration (AUC[0-t]) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin
timeFrame: Up to 25 days
measure: Part A and Part B: Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin
timeFrame: Up to 25 days
measure: Part A and Part B: Apparent Elimination Half-life (t1/2) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin
timeFrame: Up to 25 days
measure: Part A and Part B: Trough Plasma Concentration (Ctrough) of Macitentan and ACT-132577
timeFrame: Up to 25 days
measure: Part B: Number of Participants with Adverse Event as a Measure of Safety and Tolerability
timeFrame: Up to Day 45
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Actelion
name: Actelion Clinical Trial
role: STUDY_DIRECTOR
References: