Clinical trial NCT05392530: A Study of Two Different Test Formulations Compared to the Reference Formulation of Macitentan in Healthy Adult Participants
Official title: A Single-center, Open-label, Single-dose, Randomized, 3-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Relative Oral Bioavailability of Macitentan 75 mg as Two Different Test Formulations Compared to the Reference Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2022-05-26
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the rate and extent of absorption of a single oral dose of macitentan given as 2 test formulations compared to the reference formulation under fed conditions in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of physical examination and 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 millimeters of mercury (mmHg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive), within 3 minutes after standing up and after the participant is supine for at least 5 minutes, at screening
* Twelve-lead electrocardiogram (ECG) without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
* Body weight not less than 50 kilograms (Kg) and body mass index (BMI; weight/height\^2) within the range 18.5 -30 kg per meter square (kg/m\^2) (inclusive)at screening
* All women must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) pregnancy test at screening and a negative urine pregnancy test on Day -1 of the first treatment period

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient 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 intervention(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed)
* A history of repeated fainting due to cardiac cause, collapse, syncope, orthostatic hypotension, or vasovagal reactions
* Female participant who is breastfeeding at screening and plans to breastfeed throughout the study
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Primary outcomes:
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Time of the Last Quantifiable Concentration of Macitentan (AUC[0-last])
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Macitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
Secondary outcomes:
measure: Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite Aprocitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite Aprocitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Area Under the Plasma Analyte Concentration-time Curve of Macitentan and its Metabolite Aprocitentan from Time Zero to 72 Hours Post dose (AUC[0-72 Hours])
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite Aprocitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and its Metabolite Aprocitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Total Apparent Oral Clearance (CL/F) of Macitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Apparent Volume of Distribution (Vdz/F) of Macitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Time of the Last Quantifiable Concentration of Aprocitentan (AUC[0-last])
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Area Under the Plasma Analyte Concentration-Time Curve of Aprocitentan from Time Zero to Infinity (AUC[0-infinity])
timeFrame: Predose, up to 336 hours post dose (up to Day 15)
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 13 weeks
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 13 weeks
measure: Number of Participants with Abnormalities in Physical Examination
timeFrame: Up to Day 15
measure: Number of Participants with Abnormalities in Vital Signs
timeFrame: Up to Day 15
measure: Number of Participants with Abnormalities in Electrocardiograms (ECGs)
timeFrame: Up to Day 15
measure: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to Day 15
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: SGS Belgium NV
Study officials:
affiliation: Actelion
name: Actelion Clinical Trial
role: STUDY_DIRECTOR
References: