A Study to Compare the Macitentan-tadalafil Fixed Dose Combination Tablet Relative to the Concomitant Administration of the Reference Tablets of Macitentan and Tadalafil in Healthy Subjects

June 20, 2025 updated by: Actelion

Single-center, Open-label, Single-dose, Two-period, Randomized, Crossover, Phase I Study to Demonstrate Bioequivalence Between a Fixed Dose Combination Product Formulation of Macitentan/Tadalafil (10 mg/40 mg) and the Free Combination of 10 mg Macitentan (Opsumit®) and 40 mg Tadalafil (Adcirca®) in Healthy Male and Female Subjects

The primary objective of this study is to demonstrate that macitentan and tadalafil administered as a fixed combination is bioequivalent to both compounds given as separate tablets given at the same doses as in the fixed combination (i.e. whether the amounts of macitentan and tadalfil which reach the blood are comparable).

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.

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.
38

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

14 years to 51 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Key Inclusion Criteria:

  • Signed informed consent
  • Male and female subjects aged between 18 and 55 years (inclusive) at screening
  • Healthy on the basis of the physical examination, vital signs, 12-lead ECG, and laboratory tests performed at screening
  • Women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day-1 or must be of non-childbearing potential.
  • Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at screening
  • Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive)

Key Exclusion Criteria:

  • Known hypersensitivity to any active substance or drugs of the same class, or any excipients of the drug formulation(s)
  • 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)
  • Values of hepatic aminotransferase (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) > 3 X upper limit of normal at screening
  • Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy
  • Known hereditary degenerative retinal disorders, including retinitis pigmentosa
  • Priapism and anatomical deformation of the penis
  • Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
  • Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening
  • Excessive caffeine consumption, defined as > or = 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; washout period included)
  • Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications 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.

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: Randomized
  • Interventional Model: Crossover 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 A/B
Subjects receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 1, then after a washout period of at least 7 days they receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 2
Combination product: Macitentan / tadalafil FDC
Tablets for oral administration containing 10 mg of macitentan and 40 mg of tadalafil
Drug: Macitentan (Opsumit®)
Film-coated tablets for oral administration formulated at a strength of 10 mg
Other Names:
  • ACT-064992
Drug: Tadalafil (Adcirca®)
Film-coated tablets for oral administration formulated at a strength of 20 mg
Experimental: Sequence B/A
Subjects receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 1, then after a washout period of at least 7 days, they receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 2
Combination product: Macitentan / tadalafil FDC
Tablets for oral administration containing 10 mg of macitentan and 40 mg of tadalafil
Drug: Macitentan (Opsumit®)
Film-coated tablets for oral administration formulated at a strength of 10 mg
Other Names:
  • ACT-064992
Drug: Tadalafil (Adcirca®)
Film-coated tablets for oral administration formulated at a strength of 20 mg

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
Maximum plasma concentration (Cmax) of macitentan and tadalafil
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
The measured individual plasma concentrations of macitentan and tadalafil are used to directly obtain Cmax
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of macitentan and tadalafil
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-t) is the area calculated from the concentration-time profile of macitentan and tadalafil, from time 0 to to time t of the last measured concentration above the limit of quantification
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Area under the plasma concentration-time curve to infinitiy [AUC(0-inf)] of macitentan and tadalafil
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-inf) is the area calculated from the concentration-time profile of macitentan and tadalafil, from time 0 to extrapolated infinite time
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period

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
maximal plasma concentration (Cmax) of ACT-132577
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Cmax of the active metabolite of macitentan, ACT-132577, is measured directly from the plasma concentrations of ACT-132577
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of ACT-132577
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-t) of the active metabolite of macitentan, ACT-132577, is calculated from the concentration-time profile of ACT-132577 from time 0 to time t of the last measured concentration above the limit of quantification
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Area under the plasma concentration-time curve to infinity [AUC(0-inf)] of ACT-132577
Time Frame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-inf) of the active metabolite of macitentan, ACT-132577, is calculated from the concentration-time profile of ACT-132577 from time 0 to extrapolated infinite time
Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period

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: JP Jones, 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.
August 7, 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.
September 24, 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.
September 24, 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).
July 11, 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.
July 11, 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.
July 12, 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-077-103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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