A Study of Two Macitentan Pediatric Formulations in Healthy Adult Participants

NCT04963439 | Completed Phase 1

• 3 other identifiers: CR1090272021-001258-6767896062PAH1008
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the rate and extent of absorption of macitentan following administration of a single oral dose of macitentan formulated as final market image (FMI) (test), compared to macitentan as the clinical service formulation (CSF) under fasted 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 and up to 216 hours post dose (Up to Day 10)

• Area Under the Plasma Analyte Concentration-time Curve of Macitentan from Time Zero to Time of the Last Quantifiable Concentration (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, calculated by linear-linear trapezoidal summation.

  Predose and up to 216 hours post dose (Up to Day 10)

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

  AUC (0-infinity) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), where AUC (0-last) is area under the plasma analyte concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) plasma analyte concentration and lambda(z) is apparent terminal elimination rate constant.

  Predose and up to 216 hours post dose (Up to Day 10)

Secondary Outcomes (15)

• Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite ACT-132577

  Predose and up to 216 hours post dose (Up to Day 10)

• Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite ACT-132577

  Predose and up to 216 hours post dose (Up to Day 10)

• Area Under the Plasma Analyte Concentration-time Curve of Macitentan and its Metabolite ACT-132577 from Time Zero to 72 Hours (AUC [0-72 Hours]) Postdose

  Predose up to 72 hours post dose

• Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite ACT-132577

  Predose and up to 216 hours post dose (Up to Day 10)

• Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and its Metabolite ACT-132577

  Predose and up to 216 hours post dose (Up to Day 10)

Study Arms (2)

Treatment Sequence AB

EXPERIMENTAL

Participants will receive single oral dose of macitentan formulated as final market image (FMI) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of macitentan as the clinical service formulation (CSF) in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study intervention intake in subsequent intervention periods in an individual participant will be separated by a washout period of at least 10 days.

Drug: Macitentan

Treatment Sequence BA

EXPERIMENTAL

Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study intervention intake in subsequent intervention periods in an individual participant will be separated by a washout period of at least 10 days.

Drug: Macitentan

Interventions

Macitentan DRUG

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

Also known as: Opsumit, ACT-064992

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 collected 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) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
• Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and 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 50.0 kilograms (kg) and body mass index (BMI) between 18.5 and 30.0 kilograms per meter square (kg/m\^2) (inclusive)
• 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

You may not qualify if:

• Known allergies, hypersensitivity, or intolerance to macitentan or drugs of the same class, or any excipients of the drug formulations
• Taken any disallowed therapies, concomitant therapy within 14 days (or longer, based on elimination half-life) before administration of study intervention in the first intervention period
• Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days or 10 half-lives (whichever is longer) before study intervention intake in the first intervention period, or received a biological product within 3 months or 10 half-lives (whichever is longer) before study intervention intake in the first intervention period, or is currently enrolled in an investigational study
• Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (\>) 1.5 \* upper limit of normal at screening
• Positive results from the human immunodeficiency virus (HIV) (type 1 and 2) serology at screening

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, 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: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 15, 2021
• Study Start: July 8, 2021
• Primary Completion: September 12, 2021
• Study Completion: October 5, 2021
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)