Clinical trial NCT04963439: A Study of Two Macitentan Pediatric Formulations in Healthy Adult Participants
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 Two Macitentan Pediatric Formulations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2021-07-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the rate and extent of absorption of macitentan following administration of a single oral dose of macitentan formulated as final market image (FMI) (test), compared to macitentan as the clinical service formulation (CSF) under fasted conditions in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of physical examination, medical and surgical history collected 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) 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
* Body weight not less than 50.0 kilograms (kg) and body mass index (BMI) between 18.5 and 30.0 kilograms per meter square (kg/m\^2) (inclusive)
* All women must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta- hCG\]) pregnancy test at screening and must have a negative urine pregnancy test on Day -1 of each intervention period

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to macitentan or drugs of the same class, or any excipients of the drug formulations
* Taken any disallowed therapies, concomitant therapy within 14 days (or longer, based on elimination half-life) before administration of study intervention in the first intervention period
* Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days or 10 half-lives (whichever is longer) before study intervention intake in the first intervention period, or received a biological product within 3 months or 10 half-lives (whichever is longer) before study intervention intake in the first intervention period, or is currently enrolled in an investigational study
* Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (\>) 1.5 \* upper limit of normal at screening
* Positive results from the human immunodeficiency virus (HIV) (type 1 and 2) serology at screening

Primary outcomes:
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve of Macitentan from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last])
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve of Macitentan from Time Zero to Infinity (AUC [0-infinity])
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
Secondary outcomes:
measure: Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve of Macitentan and its Metabolite ACT-132577 from Time Zero to 72 Hours (AUC [0-72 Hours]) Postdose
timeFrame: Predose up to 72 hours post dose
measure: Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and its Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Total Apparent Oral Clearance (CL/F) of Macitentan and its Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Apparent Volume of Distribution (Vdz/F) of Macitentan and its Metabolite
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Metabolite ACT-132577
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Area Under the Plasma Analyte Concentration-Time Curve of Metabolite ACT-132577 from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last])
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Area Under the Plasma Analyte Concentration-Time Curve of Metabolite ACT-132577 from Time Zero to Infinity (AUC [0-infinity])
timeFrame: Predose and up to 216 hours post dose (Up to Day 10)
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 10
measure: Number of Participants with Abnormalities in Physical Examination
timeFrame: Up to Day 10 of each treatment period (Up to 7 weeks)
measure: Number of Participants with Abnormalities in Vital Signs
timeFrame: Up to Day 10 of each treatment period (Up to 7 weeks)
measure: Number of Participants with Abnormalities in Electrocardiograms (ECGs)
timeFrame: Up to Day 10 of each treatment period (Up to 7 weeks)
measure: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to Day 10 of each treatment period (Up to 7 weeks)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Actelion
name: Actelion Clinical Trial
role: STUDY_DIRECTOR
References: