Clinical trial NCT05433675: A Study of Two Macitentan 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 Bioequivalence of the Dispersible Final Market Image (FMI) Macitentan Tablet (4 x 2.5 mg) and the Opsumit Tablet (10 mg) in Fasted Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2022-06-27
Enrollment: 28
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 evaluate the bioequivalence of macitentan on the primary pharmacokinetics (PK) parameters between the dispersible final market image (FMI) macitentan tablet and the opsumit tablet in healthy adult participants in fasted conditions.


Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of physical examination, medical and surgical history performed at screening. If there are any abnormalities, they must be considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
* Body weight not less than 50 kilograms (kg) and body mass index (BMI) within the range 18.5 - 30.0 kilogram 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 must have a negative urine pregnancy test on Day -1 of each intervention period
* A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after the last study intervention intake
* Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study, before starting any screening activities

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to macitentan, fructose or drugs of the same class, or any excipients of the drug formulations
* History or clinical evidence of any disease or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study intervention (appendectomy and herniotomy allowed, cholecystectomy not allowed)
* A history of repeated fainting due to cardiac cause, collapse, syncope, orthostatic hypotension, or vasovagal reactions
* Veins unsuitable for intravenous puncture on either arm (example, veins that are difficult to locate, access, or puncture, and veins with a tendency to rupture during or after puncture)
* Woman who is breastfeeding/pregnant at screening or plans to breastfeed/become pregnant throughout the study until 30 days after last study intervention intake

Primary outcomes:
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Area Under the Plasma Analyte Concentration Versus Time Curve From Time Zero To Time of the Last Quantifiable (Non-below Quantification Limit [Non-BQL]) Concentration (AUC [0-last]) of Macitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Macitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
Secondary outcomes:
measure: Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Last Observed Measurable (Non-BQL) Plasma Analyte Concentration (Clast) of Macitentan and Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to 72 Hours Postdose (AUC [0-72 Hours]) of Macitentan and Aprocitentan
timeFrame: Predose up to 0 to 72 hours postdose (up to Day 4)
measure: Apparent Terminal Elimination Half-life (t1/2) of Macitentan and Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Total Apparent Oral Clearance (CL/F) of Macitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Apparent Volume of Distribution (Vdz/F) of Macitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Area Under the Plasma Analyte Concentration Versus Time Curve From Time Zero To Time of the Last Quantifiable (Non-BQL) Concentration (AUC [0-last]) of Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Area Under the Plasma Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Aprocitentan
timeFrame: Predose up to 216 hours postdose (up to Day 10)
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: From screening to the last follow-up visit (up to 10 weeks)
measure: Number of Participants with Abnormalities in Physical Examination
timeFrame: Up to Day 10
measure: Number of Participants with Abnormalities in Vital Signs
timeFrame: Up to Day 10
measure: Number of Participants with Abnormalities in Electrocardiogram (ECG)
timeFrame: Up to Day 10
measure: Number of Participants with Abnormalities in Clinical Laboratory Tests
timeFrame: Up to Day 10
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: SGS Belgium NV
Study officials:
affiliation: Actelion
name: Actelion Clinical Trial
role: STUDY_DIRECTOR
References: