Clinical Study to Investigate the Effect of Macitentan on the Concentrations of Rosuvastatin in the Blood of Healthy Male Subjects

June 20, 2025 updated by: Actelion

A Single-center, Open-label, One-sequence, Two-treatment Study to Investigate the Effect of Macitentan at Steady State on the Pharmacokinetics of Rosuvastatin in Healthy Male Subjects.

The aim of this Phase 1 trial is to study a potential drug-drug interaction between macitentan and rosuvastatin, a model substrate of various transporter proteins (e.g. in the gut).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Rosuvastatin is a substrate of various transporter proteins including breast cancer resistance protein (BCRP) and organic anion-transporting polypeptides (OATP). It is unknown to which extent macitentan has an effect, if any, on BCRP transporters, especially intestinal BCRP. The primary purpose of this Phase 1 study is to investigate the effect of macitentan on the pharmacokinetics of rosuvastatin, a model BCRP substrate.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Mannheim, Germany, 68167
        • CRS Clinical Research Services Mannheim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Principal Inclusion Criteria:

  • Signed informed consent in the local language prior to any study-mandated procedure.
  • Healthy male subjects aged between 18 and 55 years (inclusive) at screening.
  • No clinically significant findings on the physical examination at screening.
  • Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at screening.
  • Systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg, and pulse rate 50-90 beats per minute (inclusive), measured on the dominant arm, after 5 min in the supine position at screening.
  • 12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
  • Hematology and clinical chemistry test results not deviating from the normal range to a clinically relevant extent at screening.
  • Negative results from urine drug screen and alcohol breath test at screening and Day -1.
  • Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Principal Exclusion Criteria:

  • Known allergic reactions or hypersensitivity to macitentan, rosuvastatin, any drug of the same classes, or any of their excipients.
  • Any contraindication for rosuvastatin treatment.
  • History or clinical evidence of myopathy.
  • Subjects of Asian race.
  • Known hypersensitivity or allergy to natural rubber latex.
  • Values of hepatic aminotransferase (alanine aminotransferase and aspartate aminotransferase) outside of the normal range at screening.
  • Hemoglobin or hematocrit outside of the normal range at screening.
  • 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 treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
  • Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
  • Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
  • Previous exposure to macitentan.
  • Previous exposure to rosuvastatin.
  • Treatment with another investigational drug within 3 months prior to screening or participation in more than 3 investigational drug studies within 1 year prior to screening.
  • History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
  • Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
  • Nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum or electronic cigarettes) within 3 months prior to screening and inability to refrain from nicotine intake from screening until End-Of-Study (EOS).
  • 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.
  • Loss of 250 mL or more of blood within 3 months prior to screening.
  • Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
  • Positive results from the HIV serology at screening.
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
  • Legal incapacity or limited legal capacity at screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sequence AB
Subjects participate in two study periods: During the first period (treatment A), they receive a single oral dose of rosuvastatin on Day 1. During the second period (treatment B), they receive a single oral loading dose of macitentan on Day 5 and oral doses of macitentan from Day 6 to Day 16 (i.e., 11 doses). Subjects receive a single oral dose of 10 mg rosuvastatin concomitantly with macitentan in the morning of Day 10.
Drug: Rosuvastatin
Single oral dose of 10 mg rosuvastatin (film-coated tablet) on Day 1 and Day 10
Drug: Macitentan
Single oral dose of 30 mg macitentan (film-coated tablet) on Day 5 and 10 mg macitentan administered orally from Day 6 to Day 16
Other Names:
  • ACT-064992

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
AUC(0-inf) of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)
Time Frame: From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
AUC(0-inf) is the area under the plasma concentration-time curves of rosuvastatin, calculated from time zero to the extrapolated infinite time
From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
Cmax of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)
Time Frame: From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of rosuvastatin
From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
tmax of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)
Time Frame: From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
The time to reach maximum plasma concentration (tmax) of rosuvastatin
From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
t½ of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)
Time Frame: From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
t½ is the terminal half-life of rosuvastatin and corresponds to the period of time required for the concentration levels of rosuvastatin to be reduced by one-half
From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
AUC(0-t) of rosuvastatin following administration of rosuvastatin alone (treatment A) and in combination with macitentan (treatment B)
Time Frame: From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
AUC(0-t) is the area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification of rosuvastatin
From Day1 to Day17 (treatment A: from Day1-Day5 and treatment B: from Day10-Day17)
Trough plasma concentrations of macitentan and its metabolite ACT-132577
Time Frame: From Day5 to Day17
Trough concentrations of macitentan and ACT-132577 are measured before oral administration of macitentan
From Day5 to Day17
Change from baseline in supine blood pressure
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change from baseline to each time point of measurement during study period
From Day1 to end-of-study visit (Day 26-28)
Change from baseline in pulse rate
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change from baseline to each time point of measurement during study period
From Day1 to end-of-study visit (Day 26-28)
Change from baseline in heart rate (HR)
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change from baseline to each time point of measurement during study period
From Day1 to end-of-study visit (Day 26-28)
Change from baseline in ECG variables
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change from baseline to each time point of measurement during study period in ECG variables: PR, QRS, QT, RR, and QT corrected for Bazett's and Fridericia's formulae (QTcB and QTcF, respectively)
From Day1 to end-of-study visit (Day 26-28)
Change from baseline to end-of-study (EOS) in body weight
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change in body weight measured in kg during study period
From Day1 to end-of-study visit (Day 26-28)
Change from baseline in clinical laboratory tests
Time Frame: From Day1 to end-of-study visit (Day 26-28)
Change from baseline to each time point of measurement during study period for clinical laboratory tests (hematology, clinical chemistry, serology)
From Day1 to end-of-study visit (Day 26-28)
Incidence rate of treatment-emergent treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
Time Frame: From Day1 to follow-up period (Day46-48)
Incidence rates of treatment-emergent AEs including abnormalities in ECG variables during each treatment as well as AEs leading to the discontinuation of study treatment. A treatment-emergent AE is any AE temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
From Day1 to follow-up period (Day46-48)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Actelion

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Shirin Bruderer, PhD, Actelion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 3, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 4, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 4, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 27, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC-055-122

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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