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Completed

NCT Number: NCT04211272

A 2-part Study to Investigate the Effect of Macitentan in Healthy Male Participants

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.

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Macitentan

Drug

Macitentan will be administrated as film-coated tablet in Part A and Part B.

Other names: JNJ-67896062-AAA

Sildenafil

Drug

Sildenafil will be administrated as film-coated tablet in Part A.

Other names: Revatio

Riociguat

Drug

Riociguat will be administrated as film-coated tablet in Part A.

Other names: Adempas

Rosuvastatin

Drug

Rosuvastatin will be administrated as film-coated tablet in Part B.

Other names: Crestor

Primary outcomes

  1. 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

    Time frame: Up to 25 days

    AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve from time 0 to infinite time.

  2. Part A and Part B: Maximum Observed Plasma Analyte Concentration (Cmax) of Sildenafil, Riociguat, Rosuvastatin

    Time frame: Up to 25 days

    Cmax is defined as the maximum observed plasma analyte concentration.

Secondary outcomes

  1. 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)

    Time frame: Up to 25 days

    AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve from time 0 to infinite time.

  2. Part A: Maximum Observed Plasma Analyte Concentration (Cmax) of Desmethyl-sildenafil, M1 and ACT-132577

    Time frame: Up to 25 days

    Cmax is defined as the maximum observed plasma analyte concentration.

  3. 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

    Time frame: Up to 25 days

    AUC(0-t) is defined as area under the plasma analyte concentration-time curve from time 0 to time t of the last measured concentration above the lower limit of quantification (LLOQ), calculated according to the linear trapezoidal rule, using the measured concentration-time values above the LLOQ.

  4. Part A and Part B: Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin

    Time frame: Up to 25 days

    Tmax is defined as actual sampling time to reach maximum observed plasma analyte concentration.

  5. Part A and Part B: Apparent Elimination Half-life (t1/2) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin

    Time frame: Up to 25 days

    t1/2 is defined as the time measured for the plasma concentration to decrease by 1 half of its original concentration. It is associated with the terminal slope of the semilogarithmic drug concentration-time curve, calculated as t1/2=0.693/ lambda(z).

  6. Part A and Part B: Trough Plasma Concentration (Ctrough) of Macitentan and ACT-132577

    Time frame: Up to 25 days

    Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.

  7. Part B: Number of Participants with Adverse Event as a Measure of Safety and Tolerability

    Time frame: Up to Day 45

    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Sponsors and collaborators

Lead sponsor

Actelion

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Dec 26, 2019
Registry last updated
Mar 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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