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

Actelion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Macitentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT05392530

2022-000275-39 (EudraCT Number)

67896062PAH1012 (Other Identifier)

CR109202

Details and patient eligibility

About

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.

Enrollment: 23 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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23 participants in 6 patient groups

Treatment Sequence ABC

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Treatment Sequence BCA

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Treatment Sequence CAB

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Treatment Sequence ACB

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Treatment Sequence CBA

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Treatment Sequence BAC

Experimental group

Description:

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.

Treatment:

Drug: Macitentan