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HealthyPhase 1NCT04211272

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

A Phase 1 study testing Macitentan, Sildenafil and Riociguat in people with Healthy, run by Actelion at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Macitentan, Sildenafil and Riociguat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteBelgium
Study dates
14 Jan 2020to 19 Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Clinical Pharmacology Unit

    Merksem, 2170

Other trials in Belgium

About this study

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

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.

Conditions
Healthy
Being tested
Macitentan, Sildenafil, Riociguat, Rosuvastatin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MacitentanDrug

    Also called JNJ-67896062-AAA

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

  • SildenafilDrug

    Also called Revatio

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

  • RiociguatDrug

    Also called Adempas

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

  • RosuvastatinDrug

    Also called Crestor

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

Study groups in NCT04211272
Study groupRoleWhat they receive
Part A: Macitentan + Substrate Drug (Sildenafil/Riociguat)ExperimentalParticipants will receive a single dose of film-coated tablet of sildenafil under fasted condition (Treatment A1), then riociguat under fasted condition (Treatment A2) followed by macitentan under fed condition (Treatment B1), then riociguat along with macitentan under fasted conditions followed by macitentan under fed conditions (Treatment B2) and then sildenafil along with macitentan under fasted condition (Treatment B3). Macitentan will be administered in an up-titration regimen.
Receives: Drug: Macitentan; Drug: Sildenafil; Drug: Riociguat
Part B: Macitentan + Substrate Drug (Rosuvastatin)ExperimentalParticipants will receive a single dose of film-coated tablet of rosuvastatin under fasted condition (Treatment A1), then macitentan under fed condition (Treatment B1) followed by rosuvastatin along with macitentan under fasted condition followed by macitentan under fed condition (Treatment B2). Macitentan will be administered in an up-titration regimen. Part B of the study will be conducted depending on the results of Part A and feedback from Health Authorities.
Receives: Drug: Macitentan; Drug: Rosuvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

    Measured: Up to 25 days

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

    Cmax is defined as the maximum observed plasma analyte concentration.

    Measured: Up to 25 days

Secondary outcomes (7)

  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)

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

    Measured: Up to 25 days

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

    Cmax is defined as the maximum observed plasma analyte concentration.

    Measured: Up to 25 days

  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

    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.

    Measured: Up to 25 days

  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

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

    Measured: Up to 25 days

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

    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).

    Measured: Up to 25 days

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

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

    Measured: Up to 25 days

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

    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.

    Measured: Up to Day 45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2019
  2. Study start14 Jan 2020
  3. Primary completion19 Apr 2021
  4. Study completion19 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04211272
Sponsor's protocol ID
CR108727
Other IDs
2019-004001-27, 67896062PAH1003, 2019
Status last verified
Mar 2025
First submitted
23 Dec 2019
Last updated
30 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Publications

  • Csonka D, Gargano C, Goyal N, De Meulder M, Yartsev V, Ruixo JJP. Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants. J Clin Pharmacol. 2026 Apr;66(4):e70185. doi: 10.1002/jcph.70185.

    PubMed 42023995

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Macitentan, Sildenafil and Riociguat in people with Healthy, run by Actelion at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Up to 25 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04211272, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.

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