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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
28
Macitentan dispersible and film-coated tablets will be administered orally as per assigned treatment sequence.
SGS Belgium NV
Edegem, Belgium
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
Cmax is defined as maximum observed plasma analyte concentration of macitentan.
Time frame: 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.
Time frame: 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.
Time frame: Predose up to 216 hours postdose (up to Day 10)
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.
Time frame: Predose up to 216 hours postdose (up to Day 10)
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.
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Time frame: 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
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.
Time frame: Predose up to 0 to 72 hours postdose (up to Day 4)
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.
Time frame: Predose up to 216 hours postdose (up to Day 10)
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.
Time frame: Predose up to 216 hours postdose (up to Day 10)
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).
Time frame: Predose up to 216 hours postdose (up to Day 10)
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 \[0-infinity\]).
Time frame: Predose up to 216 hours postdose (up to Day 10)
Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan
Cmax is defined as maximum observed plasma analyte concentration of aprocitentan.
Time frame: 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-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.
Time frame: 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 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.
Time frame: Predose up to 216 hours postdose (up to Day 10)
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.
Time frame: From screening to the last follow-up visit (up to 10 weeks)
Number of Participants with Abnormalities in Physical Examination
Number of participants with abnormalities in physical examination (including height and body weight) will be reported.
Time frame: Up to Day 10
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.
Time frame: Up to Day 10
Number of Participants with Abnormalities in Electrocardiogram (ECG)
Number of participants with abnormalities in ECG will be reported.
Time frame: Up to Day 10
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.
Time frame: Up to Day 10