HealthyPhase 1NCT04540744
A Study of Macitentan/Tadalafil Combination Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of Macitentan and Tadalafil
A Phase 1 study testing FDC of macitentan/tadalafil (10 mg/20 mg), Macitentan 10 mg and Tadalafil 20 mg in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Belgium.
Trial summary
The purpose of this study is to assess the rate and extent of absorption of macitentan and tadalafil following administration of a single oral dose of a fixed-dose combination (FDC) of 10 milligram (mg)/20 mg macitentan/tadalafil (test), compared to the coadministration as a free combination (reference) of 10 mg… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- FDC of macitentan/tadalafil (10 mg/20 mg), Macitentan 10 mg and Tadalafil 20 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteBelgium
- Study dates
- 30 Apr 2021to 30 Aug 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study, before starting any screening activities
- Body mass index (BMI; weight [kg]/height^2 [m]^2) between 18.5 and 30.0 kilogram per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg at screening
- Healthy on the basis of physical examination, medical and surgical history, performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- Systolic blood pressure (SBP) between 100 and 145 millimeter of Mercury (mmHg) (inclusive) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
- Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
- During the study (from the day of first study drug intake onwards) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the last study drug intake, a male participant must agree: (a) to wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); (b) not to donate sperm for the purpose of reproduction.
- Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
Who cannot join
- Female participant who is breastfeeding at screening and/or plans to breastfeed throughout the study until 30 days after last study drug intake
- Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
- Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (>)1.5 * upper limit of normal at screening
- Any loss of vision (permanent or transient blindness in 1 or both eyes, including ophthalmic migraine, transient ischemic attack, retinal artery/vein thrombosis)
- Known hereditary degenerative retinal disorders, including retinitis pigmentosa
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label, Single-dose, Randomized, 2-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Relative Oral Bioavailability of the Combination of Macitentan/Tadalafil (10 mg/20 mg) Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of 10 mg Macitentan (Opsumit®) and 20 mg Tadalafil (Adcirca®)
The purpose of this study is to assess the rate and extent of absorption of macitentan and tadalafil following administration of a single oral dose of a fixed-dose combination (FDC) of 10 milligram (mg)/20 mg macitentan/tadalafil (test), compared to the coadministration as a free combination (reference) of 10 mg macitentan and 20 mg tadalafil under fasted conditions in healthy adult participants.
- Conditions
- Healthy
- Being tested
- FDC of macitentan/tadalafil (10 mg/20 mg), Macitentan 10 mg, Tadalafil 20 mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FDC of macitentan/tadalafil (10 mg/20 mg)Drug
Also called Opsumit, Adcirca
FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence.
Macitentan 10 mgDrug
Also called Opsumit
Macitentan 10 mg tablet will be administered orally as a free combination as per assigned treatment sequence.
Tadalafil 20 mgDrug
Also called Adcirca
Tadalafil 20 mg tablet will be administered orally as a free combination as per assigned treatment sequence.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence AB | Experimental | Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days. Receives: Drug: FDC of macitentan/tadalafil (10 mg/20 mg); Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg |
| Treatment Sequence BA | Experimental | Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days. Receives: Drug: FDC of macitentan/tadalafil (10 mg/20 mg); Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan, its Metabolite ACT-132577, and Tadalafil
Cmax is defined as maximum observed plasma analyte concentration.
Measured: Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
AUC(0-last) is the area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
Measured: Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
Measured: Predose and up to 216 hours post dose (Up to Day 10)
Secondary outcomes (1)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
An AE 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 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2020
- Study start30 Apr 2021
- Primary completion8 Aug 2021
- Study completion30 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04540744
- Sponsor's protocol ID
- CR108794
- Other IDs
- 2020-000566-42, 67896062PAH1001
- Status last verified
- Mar 2025
- First submitted
- 2 Sep 2020
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Single-dose, Randomized, 2-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Relative Oral Bioavailability of the Combination of Macitentan/Tadalafil (10 mg/20 mg) Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of 10 mg Macitentan (Opsumit®) and 20 mg Tadalafil (Adcirca®)
- ClinicalTrials.gov ID
- NCT04540744
- Acronym / sponsor ID
- CR108794
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2021 (actual)
- Primary completion
- 8 Aug 2021 (actual)
- Study completion
- 30 Aug 2021 (actual)
- First posted
- 7 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the rate and extent of absorption of macitentan and tadalafil following administration of a single oral dose of a fixed-dose combination (FDC) of 10 milligram (mg)/20 mg macitentan/tadalafil (test), compared to the coadministration as a free combination (reference) of 10 mg macitentan and 20 mg tadalafil under fasted conditions in healthy adult participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence AB | Experimental | Drug: FDC of macitentan/tadalafil (10 mg/20 mg), Drug: Macitentan 10 mg, Drug: Tadalafil 20 mgParticipants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days. |
| Treatment Sequence BA | Experimental | Drug: FDC of macitentan/tadalafil (10 mg/20 mg), Drug: Macitentan 10 mg, Drug: Tadalafil 20 mgParticipants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study, before starting any screening activities
- Body mass index (BMI; weight [kg]/height^2 [m]^2) between 18.5 and 30.0 kilogram per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg at screening
- Healthy on the basis of physical examination, medical and surgical history, performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- Systolic blood pressure (SBP) between 100 and 145 millimeter of Mercury (mmHg) (inclusive) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
- Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
Key exclusion criteria (5 listed)
- Female participant who is breastfeeding at screening and/or plans to breastfeed throughout the study until 30 days after last study drug intake
- Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
- Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (>)1.5 * upper limit of normal at screening
- Any loss of vision (permanent or transient blindness in 1 or both eyes, including ophthalmic migraine, transient ischemic attack, retinal artery/vein thrombosis)
- Known hereditary degenerative retinal disorders, including retinitis pigmentosa
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FDC of macitentan/tadalafil (10 mg/20 mg)Also: Opsumit, AdcircaFDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence. | Drug | Treatment Sequence AB, Treatment Sequence BA |
| Macitentan 10 mgAlso: OpsumitMacitentan 10 mg tablet will be administered orally as a free combination as per assigned treatment sequence. | Drug | Treatment Sequence AB, Treatment Sequence BA |
| Tadalafil 20 mgAlso: AdcircaTadalafil 20 mg tablet will be administered orally as a free combination as per assigned treatment sequence. | Drug | Treatment Sequence AB, Treatment Sequence BA |
Primary outcome
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan, its Metabolite ACT-132577, and Tadalafil
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Cmax is defined as maximum observed plasma analyte concentration.
Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
AUC(0-last) is the area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
1 secondary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Up to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FDC of macitentan/tadalafil (10 mg/20 mg), Macitentan 10 mg and Tadalafil 20 mg in people with Healthy, run by Janssen Research & Development, LLC 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 7 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?
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan, its Metabolite ACT-132577, and Tadalafil (time frame: Predose and up to 216 hours post dose (Up to Day 10)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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; AzTrials last refreshed its copy on 2 Nov 2026.