Healthy SubjectsPhase 1NCT03215966
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
A Phase 1 study testing Macitentan / tadalafil FDC, Macitentan (Opsumit®) and Tadalafil (Adcirca®) in people with Healthy Subjects, run by Actelion at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- Macitentan / tadalafil FDC, Macitentan (Opsumit®) and Tadalafil (Adcirca®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteGermany
- Study dates
- 7 Aug 2017to 24 Sep 2017
- 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
- 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)
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
- Conditions
- Healthy Subjects
- Being tested
- Macitentan / tadalafil FDC, Macitentan (Opsumit®), Tadalafil (Adcirca®)
- Keywords
- bioequivalence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan / tadalafil FDCCombination product
Tablets for oral administration containing 10 mg of macitentan and 40 mg of tadalafil
Macitentan (Opsumit®)Drug
Also called ACT-064992
Film-coated tablets for oral administration formulated at a strength of 10 mg
Tadalafil (Adcirca®)Drug
Film-coated tablets for oral administration formulated at a strength of 20 mg
| Study group | Role | What they receive |
|---|---|---|
| Sequence A/B | Experimental | 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 Receives: Combination Product: Macitentan / tadalafil FDC; Drug: Macitentan (Opsumit®); Drug: Tadalafil (Adcirca®) |
| Sequence B/A | Experimental | 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 Receives: Combination Product: Macitentan / tadalafil FDC; Drug: Macitentan (Opsumit®); Drug: Tadalafil (Adcirca®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of macitentan and tadalafil
The measured individual plasma concentrations of macitentan and tadalafil are used to directly obtain Cmax
Measured: 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
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
Measured: 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
AUC(0-inf) is the area calculated from the concentration-time profile of macitentan and tadalafil, from time 0 to extrapolated infinite time
Measured: 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 outcomes (3)
maximal plasma concentration (Cmax) of ACT-132577
Cmax of the active metabolite of macitentan, ACT-132577, is measured directly from the plasma concentrations of ACT-132577
Measured: 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
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
Measured: 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
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
Measured: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study start7 Aug 2017
- Primary completion24 Sep 2017
- Study completion24 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- JP Jones, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03215966
- Sponsor's protocol ID
- AC-077-103
- Status last verified
- Jun 2025
- First submitted
- 11 Jul 2017
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03215966
- Acronym / sponsor ID
- AC-077-103
- Conditions
- Healthy Subjects
- Keywords
- bioequivalence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 24 Sep 2017 (actual)
- Study completion
- 24 Sep 2017 (actual)
- First posted
- 12 Jul 2017 (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 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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A/B | Experimental | Combination Product: Macitentan / tadalafil FDC, Drug: Macitentan (Opsumit®), Drug: Tadalafil (Adcirca®)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 |
| Sequence B/A | Experimental | Combination Product: Macitentan / tadalafil FDC, Drug: Macitentan (Opsumit®), Drug: Tadalafil (Adcirca®)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 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Macitentan / tadalafil FDCTablets for oral administration containing 10 mg of macitentan and 40 mg of tadalafil | Combination product | Sequence A/B, Sequence B/A |
| Macitentan (Opsumit®)Also: ACT-064992Film-coated tablets for oral administration formulated at a strength of 10 mg | Drug | Sequence A/B, Sequence B/A |
| Tadalafil (Adcirca®)Film-coated tablets for oral administration formulated at a strength of 20 mg | Drug | Sequence A/B, Sequence B/A |
Primary outcome
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
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
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
3 secondary outcomes
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
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
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
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 22 Jun 2025.
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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.
JP Jones study director
Actelion
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 Macitentan / tadalafil FDC, Macitentan (Opsumit®) and Tadalafil (Adcirca®) in people with Healthy Subjects, run by Actelion at 1 site in Germany.
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 6 inclusion and 12 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 22 Jun 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 Germany. 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 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 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 22 Jun 2025.