A Study of Two Macitentan Formulations in Healthy Adult Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Macitentan

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • SGS Belgium NV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence AB; Participants will receive single oral dose of macitentan formulated as dispersible final market image (FMI) in fasted conditions (test) (Treatment A) in Intervention Period 1 followed by a single oral dose of film-coated opsumit tablet in fasted conditions (reference) (Treatment B) in Intervention Period 2 on Day 1. There will be washout period of at least 10 days between two period.	Drug: Macitentan; Macitentan dispersible and film-coated tablets will be administered orally as per assigned treatment sequence.; Other Names: Opsumit; ACT-064992; JNJ-67896062
Experimental: Treatment Sequence BA; Participants will receive Treatment B in Intervention Period 1 followed Treatment A in Intervention Period 2 on Day 1. There will be washout period of at least 10 days between two period.	Drug: Macitentan; Macitentan dispersible and film-coated tablets will be administered orally as per assigned treatment sequence.; Other Names: Opsumit; ACT-064992; JNJ-67896062

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan	Cmax is defined as maximum observed plasma analyte concentration of macitentan.	Predose up to 216 hours postdose (up to Day 10)
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	AUC (0-last) is defined as area under the plasma analyte concentration versus time curve from time 0 to time of the last quantifiable (non-BQL) concentration of macitentan.	Predose up to 216 hours postdose (up to Day 10)
Area Under the Plasma Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Macitentan	AUC (0-infinity) is defined as the area under the plasma analyte concentration-time curve from time 0 to infinite time of macitentan, calculated as the summation of AUC(0-last) and C(last)/lambda(z); where AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) plasma analyte concentration, and lambda(z) is apparent terminal elimination rate constant.	Predose up to 216 hours postdose (up to Day 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and Aprocitentan	Tmax is defined as actual sampling time to reach the maximum observed plasma analyte concentration of macitentan and aprocitentan.	Predose up to 216 hours postdose (up to Day 10)
Last Observed Measurable (Non-BQL) Plasma Analyte Concentration (Clast) of Macitentan and Aprocitentan	Clast is defined as last observed measurable (non-BQL) plasma analyte concentration of macitentan and aprocitentan.	Predose up to 216 hours postdose (up to Day 10)
Area Under the Plasma Analyte Concentration-time Curve from Time Zero to 72 Hours Postdose (AUC [0-72 Hours]) of Macitentan and Aprocitentan	AUC (0-72 hours) is defined as area under the plasma analyte concentration-time curve from time 0 to 72 hours postdose of macitentan and aprocitentan calculated by linear-linear trapezoidal summation.	Predose up to 0 to 72 hours postdose (up to Day 4)
Apparent Terminal Elimination Half-life (t1/2) of Macitentan and Aprocitentan	t1/2 is defined as apparent terminal elimination half-life of macitentan and aprocitentan, calculated as 0.693/lambda(z); where lambda(z) is apparent terminal elimination rate constant.	Predose up to 216 hours postdose (up to Day 10)
Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and Aprocitentan	Lambda(z) is defined as apparent terminal elimination rate constant of macitentan and aprocitentan, estimated by linear regression using the terminal log-linear phase of the log transformed concentration versus time curve.	Predose up to 216 hours postdose (up to Day 10)
Total Apparent Oral Clearance (CL/F) of Macitentan	CL/F is defined as total apparent oral clearance of macitentan, calculated as dose/AUC (0-infinity).	Predose up to 216 hours postdose (up to Day 10)
Apparent Volume of Distribution (Vdz/F) of Macitentan	Vdz/F of macitentan is defined as apparent volume of distribution of macitentan, calculated as dose/(Lambda[z]*AUC [0-infinity]).	Predose up to 216 hours postdose (up to Day 10)
Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan	Cmax is defined as maximum observed plasma analyte concentration of aprocitentan.	Predose up to 216 hours postdose (up to Day 10)
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	AUC (0-last) is defined as area under the plasma analyte concentration versus time curve from time 0 to time of the last quantifiable (non-BQL) concentration of aprocitentan.	Predose up to 216 hours postdose (up to Day 10)
Area Under the Plasma Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Aprocitentan	AUC (0-infinity) is defined as the area under the plasma analyte concentration-time curve from time 0 to infinite time of aprocitentan, calculated as the summation of AUC(0-last) and C(last)/lambda(z); where AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) plasma analyte concentration, and lambda(z) is apparent terminal elimination rate constant.	Predose up to 216 hours postdose (up to Day 10)
Number of Participants with Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event. An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product.	From screening to the last follow-up visit (up to 10 weeks)
Number of Participants with Abnormalities in Physical Examination	Number of participants with abnormalities in physical examination (including height and body weight) will be reported.	Up to Day 10
Number of Participants with Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs (including blood pressure, pulse/heart rate and oral temperature) will be reported.	Up to Day 10
Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	Up to Day 10
Number of Participants with Abnormalities in Clinical Laboratory Tests	Number of participants with abnormalities in clinical laboratory tests (including hematology, serum chemistry, coagulation, serology and urinalysis) will be reported.	Up to Day 10

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Actelion Clinical Trial, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): October 3, 2022

Study Registration Dates

• First Submitted: June 22, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Endothelin A Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: CR109185; 67896062PAH1010 (Other Identifier: Actelion); 2022-000262-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No