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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
16
Macitentan dispersible tablets will be administered orally as per assigned treatment sequence.
Clinical Pharmacology Unit
Merksem, Belgium
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
Cmax is defined as maximum observed plasma analyte concentration of Macitentan.
Time frame: 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.
Time frame: 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.
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite ACT-132577
Tmax is defined as actual sampling time to reach the maximum observed plasma analyte concentration of macitentan and its metabolite ACT-132577.
Time frame: 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
Clast is defined as last observed measurable BQL plasma analyte concentration of macitentan and its metabolite ACT-132577.
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Time frame: 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
AUC (0-72 hours) is defined as area under the plasma analyte concentration-time curve of macitentan and its metabolite ACT-132577 from time zero to 72 hours postdose, calculated by linear-linear trapezoidal summation.
Time frame: Predose up to 72 hours post dose
Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite ACT-132577
t1/2 of macitentan and its metabolite ACT-132577 is time measured for the plasma analyte concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: 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
Lambda(z) of macitentan and its metabolite ACT-132577 is defined as apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log transformed concentration versus time curve.
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Total Apparent Oral Clearance (CL/F) of Macitentan and its Metabolite ACT-132577
CL/F of macitentan and its metabolite ACT-132577 is defined as total apparent oral clearance, calculated as dose/AUC (0-infinity).
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Apparent Volume of Distribution (Vdz/F) of Macitentan and its Metabolite
Vdz/F of macitentan and its metabolite ACT-132577 is defined as apparent volume of distribution, calculated as dose/(Lambda\[z\]\*AUC \[0-infinity\]).
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Maximum Observed Plasma Analyte Concentration (Cmax) of Metabolite ACT-132577
Cmax is defined as maximum observed plasma analyte concentration of metabolite ACT-132577.
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Plasma Analyte Concentration-Time Curve of Metabolite ACT-132577 from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-last])
AUC (0-last) of metabolite ACT-132577 is defined as area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (BQL) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Area Under the Plasma Analyte Concentration-Time Curve of Metabolite ACT-132577 from Time Zero to Infinity (AUC [0-infinity])
AUC (0-infinity) is defined as area under the plasma analyte concentration-time curve of metabolite ACT-132577 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.
Time frame: Predose and up to 216 hours post dose (Up to Day 10)
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Up to Week 10
Number of Participants with Abnormalities in Physical Examination
Number of participants with abnormalities in physical examination (including general appearance, respiratory, neurological, eyes, ear/nose/throat, thyroid, cardiovascular, abdominal/gastrointestinal, hepatic, musculoskeletal, and dermatologic) will be reported.
Time frame: Up to Day 10 of each treatment period (Up to 7 weeks)
Number of Participants with Abnormalities in Vital Signs
Number of participants with abnormalities in vital signs (including temperature \[tympanic\], pulse rate, and blood pressure) will be reported.
Time frame: Up to Day 10 of each treatment period (Up to 7 weeks)
Number of Participants with Abnormalities in Electrocardiograms (ECGs)
Number of participants with abnormalities in ECGs will be reported.
Time frame: Up to Day 10 of each treatment period (Up to 7 weeks)
Number of Participants with Abnormalities in Clinical Laboratory Tests
Number of participants with abnormalities in clinical laboratory tests (such as serum chemistry, hematology, and urinalysis) will be reported.
Time frame: Up to Day 10 of each treatment period (Up to 7 weeks)