A Study of Two Macitentan Formulations in Healthy Adult Participants

NCT05433675 | Completed Phase 1

• 3 other identifiers: CR10918567896062PAH10102022-000262-17
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (15)

• Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) 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

  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

  Predose up to 0 to 72 hours postdose (up to Day 4)

• Apparent Terminal Elimination Half-life (t1/2) of Macitentan and Aprocitentan

  Predose up to 216 hours postdose (up to Day 10)

• Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and Aprocitentan

  Predose up to 216 hours postdose (up to Day 10)

Study Arms (2)

Treatment Sequence AB

EXPERIMENTAL

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

Treatment Sequence BA

EXPERIMENTAL

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

Interventions

Macitentan DRUG

Macitentan dispersible and film-coated tablets will be administered orally as per assigned treatment sequence.

Also known as: Opsumit, ACT-064992, JNJ-67896062

Treatment Sequence AB; Treatment Sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

SGS Belgium NV

Edegem, 2650, Belgium

Location

MeSH Terms

Interventions

macitentan

Study Officials

• Actelion Clinical Trial

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: June 27, 2022
• Study Start: June 22, 2022
• Primary Completion: August 31, 2022
• Study Completion: October 3, 2022
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)