A Study of Two Different Test Formulations Compared to the Reference Formulation of Macitentan in Healthy Adult Participants

NCT05392530 | Completed Phase 1

• 3 other identifiers: CR1092022022-000275-3967896062PAH1012
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

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 336 hours post dose (up to Day 15)

• Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Time of the Last Quantifiable Concentration of Macitentan (AUC[0-last])

  AUC(0-last) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to time of the last quantifiable (non-below quantification limit \[BQL\]) concentration.

  Predose, up to 336 hours post dose (up to Day 15)

• 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 area under the plasma analyte concentration-time curve of macitentan from time zero to infinite time.

  Predose, up to 336 hours post dose (up to Day 15)

Secondary Outcomes (16)

• Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite Aprocitentan

  Predose, up to 336 hours post dose (up to Day 15)

• Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite Aprocitentan

  Predose, up to 336 hours post dose (up to Day 15)

• 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])

  Predose, up to 336 hours post dose (up to Day 15)

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

  Predose, up to 336 hours post dose (up to Day 15)

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

  Predose, up to 336 hours post dose (up to Day 15)

Study Arms (6)

Treatment Sequence ABC

EXPERIMENTAL

Participants will receive single oral dose of final marketing image (FMI) candidate #1 of macitentan (Treatment A \[test\]) under fed condition in Treatment Period 1, followed by single oral dose of FMI candidate #2 of macitentan (Treatment B \[test\]) under fed conditions in Treatment Period 2, and then single oral dose of the reference formulation of macitentan (Treatment C) under fed conditions in Treatment Period 3. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Treatment Sequence BCA

EXPERIMENTAL

Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Treatment Sequence CAB

EXPERIMENTAL

Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Treatment Sequence ACB

EXPERIMENTAL

Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Treatment Sequence CBA

EXPERIMENTAL

Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Treatment Sequence BAC

EXPERIMENTAL

Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in treatment period 2, and then Treatment C in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.

Drug: Macitentan

Interventions

Macitentan DRUG

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

Also known as: Opsumit

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

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 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

You may not qualify if:

• 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

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: May 23, 2022
• First Posted: May 26, 2022
• Study Start: May 25, 2022
• Primary Completion: August 30, 2022
• Study Completion: September 14, 2022
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)