A Study of Two Macitentan Formulations in Healthy Adult Participants

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05433675
• Other study ID #: CR109185
• Secondary ID: 67896062PAH10102
• Status: Completed
• Phase: Phase 1
• Start date: June 22, 2022
• Est. completion date: October 3, 2022

Study information

• Verified date: October 2022
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 3, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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

Locations

Country	Name	City	State
Belgium	SGS Belgium NV	Edegem

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	Up to Day 10
Secondary	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