HealthyPhase 1NCT02050802
Study to Assess the Effect of Macitentan on the Electrocardiogram (ECG) in Healthy Male and Female Subjects
A Phase 1 study testing Moxifloxacin 400 mg, Macitentan 10 mg and Macitentan 30 mg in people with Healthy, run by Actelion.
Trial summary
The study is intended to demonstrate that macitentan does not have an effect on cardiac repolarization exceeding the threshold of regulatory concern after repeated administration of daily oral doses of 10 and 30 mg to healthy male and female subjects. 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?
- Moxifloxacin 400 mg, Macitentan 10 mg and Macitentan 30 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- No sites listed yet
- Study dates
- Aug 2011to Nov 2011
- 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
- Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
- Males and females aged ≥ 18 and ≤ 55 years at screening.
- Women of childbearing potential must have had a negative pre-treatment serum pregnancy test and used consistently and correctly 2 methods of contraception at the same time from screening and up to 30 days after study treatment discontinuation. Abstinence was not considered a reliable method of contraception.
- Healthy on the basis of medical history and the assessments performed at screening.
- Physical examination without clinically relevant abnormalities at screening.
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- Body mass index (BMI) ≥ 18.0 and ≤ 28.0 kg/m^2 at screening. Body weight at least 50.0 kg.
- Negative results from urine drug screen and alcohol test at screening.
- Willing and able to refrain from alcohol consumption from study start to the end of the study.
- Negative human immunodeficiency virus (HIV) serology and hepatitis serology at screening.
- Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and heart rate (HR) 45-90 bpm (all inclusive), measured on the dominant arm (dominant arm = writing arm).
- 12-lead ECG without clinically relevant abnormalities at screening and on Day 1 prior to drug administration.
- Hematology, blood chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening and on Day 1 prior to drug administration.
Who cannot join
- Known hypersensitivity to any excipients of the drug formulations.
- Treatment with macitentan or another investigational drug in the 3 months prior to screening.
- History or clinical evidence of any disease and/or the existence of any surgical or medical condition, which might have interfered with the absorption, distribution, metabolism, or excretion of macitentan and moxifloxacin (except appendectomy and herniotomy).
- History or clinical evidence of drug abuse, alcoholism, or psychiatric disease within the 3 year period prior to screening.
- Caffeine consumption ≥ 800 mg per day at screening.
- History of fainting, collapse, syncope, blackouts, orthostatic hypotension, or vasovagal reactions.
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- Chronic or relevant acute infections.
- History of relevant allergy/hypersensitivity.
- Previous treatment with any prescribed or over-the-counter medications or herbal remedies (including herbal medicines such as St John's Wort) within 2 weeks prior to first dosing or during the trial.
- Smoking and use of tobacco substitutes or nicotine substitutes.
- Loss of 250 mL or more blood in the 3 months prior to dosing (including blood donation).
- Positive results from the hepatitis serology at screening, except for vaccinated subjects.
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the upper limit of normal prior to randomization.
- Excessive physical activities within 1 week prior to randomization.
- Any cardiac condition (including ECG abnormalities) or illness with a potential to increase the cardiac risk of the subject or that might affect the corrected QT analysis (QTc).
- QTc > 450 ms or > 470 ms (using the ECG machine heart rate-correction method) before randomization for male or female subjects, respectively.
- Subjects with personal or family history of long-QT syndrome or hypokalemia.
- Legal incapacity or limited legal capacity at screening.
- Veins unsuitable for intravenous (i.v.) 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).
- Vulnerable subjects (e.g., persons kept in detention).
- Employee of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, Four-way Crossover Phase 1 Study Including an Open-label Positive Control (Moxifloxacin) to Assess the Effect of Repeated Daily Doses of 10 mg and 30 mg Macitentan on the QT/QTc Interval of the ECG in Healthy Male and Female Subjects
The study is intended to demonstrate that macitentan does not have an effect on cardiac repolarization exceeding the threshold of regulatory concern after repeated administration of daily oral doses of 10 and 30 mg to healthy male and female subjects.
- Conditions
- Healthy
- Being tested
- Moxifloxacin 400 mg, Macitentan 10 mg, Macitentan 30 mg, Placebo
- Keywords
- Macitentan, Pharmacokinetics, Pharmacodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moxifloxacin 400 mgDrug
Macitentan 10 mgDrug
Also called Opsumit
Macitentan 30 mgDrug
Also called Opsumit
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Treatment sequence BCAD | Experimental | Subjects received study medication in the sequence BCAD. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence ABDC | Experimental | Subjects received study medication in the sequence ABDC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence DACB | Experimental | Subjects received study medication in the sequence DACB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence CDBA | Experimental | Subjects received study medication in the sequence CDBA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence DBAC | Experimental | Subjects received study medication in the sequence DBAC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence ADCB | Experimental | Subjects received study medication in the sequence ADCB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence CABD | Experimental | Subjects received study medication in the sequence CABD . Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
| Treatment sequence BCDA | Experimental | Subjects received study medication in the sequence BCDA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. Receives: Drug: Moxifloxacin 400 mg; Drug: Macitentan 10 mg; Drug: Macitentan 30 mg; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline-adjusted placebo-corrected QT interval according to Fridericia's correction (QTcF)
The QTcF interval was obtained directly from the Holter ECG monitoring.Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose). The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate)
Measured: Day 8
Secondary outcomes (15)
Placebo corrected change from baseline in heart rate on Day 8
Heart rate was obtained directly from the Holter ECG monitoring. Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose).
Measured: Day 8
Placebo corrected change from baseline in RR interval (the interval from the onset of one QRS complex to the onset of the next QRS complex) on Day 8
The RR interval was obtained directly from the Holter ECG monitoring. Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose).
Measured: Day 8
Placebo corrected change from baseline in PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) on Day 8
The PR interval was obtained directly from the Holter ECG monitoring. Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose).
Measured: Day 8
Placebo corrected change from baseline in QRS interval (time interval from the beginning of the Q wave to the end of the S wave) on Day 8
The QRS interval was obtained directly from the Holter ECG monitoring. Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose).
Measured: Day 8
Number of participants with treatment emergent ECG abnormalities
ECG were obtained from continuous 12-lead Holter ECG recordings. Morphological analyses were performed with regard to the ECG waveform interpretation for the following abnormalities: second degree heart block, third degree heart block, complete right bundle branch block, complete left bundle branch block, ST-segment change (elevation and depression separately), T-wave abnormalities (negative T waves only), and myocardial infarction pattern, and any new abnormal U waves.
Measured: 8 Days
Maximum plasma concentration (Cmax) of macitentan on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. Cmax was calculated on the basis of the blood sampling time points.
Measured: Day 8
Maximum plasma concentration (Cmax) of the macitentan metabolite ACT-132577 on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. Cmax was calculated on the basis of the blood sampling time points.
Measured: Day 8
Time to reach maximum plasma concentration (tmax) of macitentan on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. tmax was calculated on the basis of the blood sampling time points.
Measured: Day 8
Time to reach maximum plasma concentration (tmax) of the macitentan metabolite ACT-132577 on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. tmax was calculated on the basis of the blood sampling time points.
Measured: Day 8
Area under the plasma concentration-time curve over a dosing interval (AUCτ) of macitentan on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. AUCτ was calculated using the linear trapezoidal rule using the measured concentration-time values above the limit of quantification from time 0 to 24 hours after drug administration.
Measured: Day 8
Area under the plasma concentration-time curve over a dosing interval (AUCτ) of the macitentan metabolite ACT-132577 on Day 8
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with macitentan, and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, and 24 hours after dosing. AUCτ was calculated using the linear trapezoidal rule using the measured concentration-time values above the limit of quantification from time 0 to 24 hours after drug administration.
Measured: Day 8
Change from baseline to Day 8 in systolic blood pressure (SBP)
SBP was measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements were taken from the subject in a supine position after having rested for a 10-minute period.
Measured: 8 days
Change from baseline to Day 8 in diastolic blood pressure (DBP)
DBP was measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements were taken from the subject in a supine position after having rested for a 10-minute period.
Measured: 8 days
Change from baseline to Day 8 in heart rate
Heart rate was measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements were taken from the subject in a supine position after having rested for a 10-minute period.
Measured: 8 days
Change from baseline to Day 8 in body weight
Body weight was measured using the same weighing scale for all subjects and throughout the study. The weighing scale had a precision of at least 0.5 kg.
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2014 (estimated)
- Study startAug 2011
- Primary completionNov 2011
- Study completionNov 2011
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.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicolas Lindegger, PhD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02050802
- Sponsor's protocol ID
- AC-055-114
- Status last verified
- Jan 2025
- First submitted
- 29 Jan 2014
- Last updated
- 3 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, Four-way Crossover Phase 1 Study Including an Open-label Positive Control (Moxifloxacin) to Assess the Effect of Repeated Daily Doses of 10 mg and 30 mg Macitentan on the QT/QTc Interval of the ECG in Healthy Male and Female Subjects
- ClinicalTrials.gov ID
- NCT02050802
- Acronym / sponsor ID
- AC-055-114
- Conditions
- Healthy
- Keywords
- Macitentan, Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 31 Jan 2014 (estimated)
- 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 study is intended to demonstrate that macitentan does not have an effect on cardiac repolarization exceeding the threshold of regulatory concern after repeated administration of daily oral doses of 10 and 30 mg to healthy male and female subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Treatment sequence BCAD | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence BCAD. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence ABDC | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence ABDC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence DACB | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence DACB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence CDBA | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence CDBA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence DBAC | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence DBAC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence ADCB | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence ADCB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence CABD | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence CABD . Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence BCDA | Experimental | Drug: Moxifloxacin 400 mg, Drug: Macitentan 10 mg, Drug: Macitentan 30 mg, Other: PlaceboSubjects received study medication in the sequence BCDA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.
- Males and females aged ≥ 18 and ≤ 55 years at screening.
- Women of childbearing potential must have had a negative pre-treatment serum pregnancy test and used consistently and correctly 2 methods of contraception at the same time from screening and up to 30 days after study treatment discontinuation. Abstinence was not considered a reliable method of contraception.
- Healthy on the basis of medical history and the assessments performed at screening.
Key exclusion criteria (21 listed)
- Known hypersensitivity to any excipients of the drug formulations.
- Treatment with macitentan or another investigational drug in the 3 months prior to screening.
- History or clinical evidence of any disease and/or the existence of any surgical or medical condition, which might have interfered with the absorption, distribution, metabolism, or excretion of macitentan and moxifloxacin (except appendectomy and herniotomy).
- History or clinical evidence of drug abuse, alcoholism, or psychiatric disease within the 3 year period prior to screening.
- Caffeine consumption ≥ 800 mg per day at screening.
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 |
|---|---|---|
| Moxifloxacin 400 mg | Drug | Treatment sequence ABDC, Treatment sequence ADCB, Treatment sequence BCAD, Treatment sequence BCDA, Treatment sequence CABD, Treatment sequence CDBA, Treatment sequence DACB, Treatment sequence DBAC |
| Macitentan 10 mgAlso: Opsumit | Drug | Treatment sequence ABDC, Treatment sequence ADCB, Treatment sequence BCAD, Treatment sequence BCDA, Treatment sequence CABD, Treatment sequence CDBA, Treatment sequence DACB, Treatment sequence DBAC |
| Macitentan 30 mgAlso: Opsumit | Drug | Treatment sequence ABDC, Treatment sequence ADCB, Treatment sequence BCAD, Treatment sequence BCDA, Treatment sequence CABD, Treatment sequence CDBA, Treatment sequence DACB, Treatment sequence DBAC |
| Placebo | Other | Treatment sequence ABDC, Treatment sequence ADCB, Treatment sequence BCAD, Treatment sequence BCDA, Treatment sequence CABD, Treatment sequence CDBA, Treatment sequence DACB, Treatment sequence DBAC |
Primary outcome
Baseline-adjusted placebo-corrected QT interval according to Fridericia's correction (QTcF)
Time frame: Day 8
The QTcF interval was obtained directly from the Holter ECG monitoring.Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose). The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate)
15 secondary outcomes
Placebo corrected change from baseline in heart rate on Day 8
Time frame: Day 8
Placebo corrected change from baseline in RR interval (the interval from the onset of one QRS complex to the onset of the next QRS complex) on Day 8
Time frame: Day 8
Placebo corrected change from baseline in PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) on Day 8
Time frame: Day 8
Placebo corrected change from baseline in QRS interval (time interval from the beginning of the Q wave to the end of the S wave) on Day 8
Time frame: Day 8
Number of participants with treatment emergent ECG abnormalities
Time frame: 8 Days
Maximum plasma concentration (Cmax) of macitentan on Day 8
Time frame: Day 8
Maximum plasma concentration (Cmax) of the macitentan metabolite ACT-132577 on Day 8
Time frame: Day 8
Time to reach maximum plasma concentration (tmax) of macitentan on Day 8
Time frame: Day 8
Time to reach maximum plasma concentration (tmax) of the macitentan metabolite ACT-132577 on Day 8
Time frame: Day 8
Area under the plasma concentration-time curve over a dosing interval (AUCτ) of macitentan on Day 8
Time frame: Day 8
Area under the plasma concentration-time curve over a dosing interval (AUCτ) of the macitentan metabolite ACT-132577 on Day 8
Time frame: Day 8
Change from baseline to Day 8 in systolic blood pressure (SBP)
Time frame: 8 days
Change from baseline to Day 8 in diastolic blood pressure (DBP)
Time frame: 8 days
Change from baseline to Day 8 in heart rate
Time frame: 8 days
Change from baseline to Day 8 in body weight
Time frame: 8 days
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 3 Feb 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.
Nicolas Lindegger, PhD study director
Actelion
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Moxifloxacin 400 mg, Macitentan 10 mg and Macitentan 30 mg in people with Healthy, run by Actelion.
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 13 inclusion and 21 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 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
Baseline-adjusted placebo-corrected QT interval according to Fridericia's correction (QTcF) (time frame: Day 8). 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 3 Feb 2025.