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 336 hours post dose (up to Day 15) |
|
Primary |
Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Time of the Last Quantifiable Concentration of Macitentan (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. |
Predose, up to 336 hours post dose (up to Day 15) |
|
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 area under the plasma analyte concentration-time curve of macitentan from time zero to infinite time. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite Aprocitentan |
Tmax is defined as actual sampling time to reach the maximum observed plasma analyte concentration of macitentan and its metabolite aprocitentan. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite Aprocitentan |
Clast is defined as last observed measurable plasma analyte concentration of macitentan and its metabolite aprocitentan. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Area Under the Plasma Analyte Concentration-time Curve of Macitentan and its Metabolite Aprocitentan from Time Zero to 72 Hours Post dose (AUC[0-72 Hours]) |
AUC(0-72 hours) is defined as area under the plasma analyte concentration-time curve of macitentan and its metabolite aprocitentan from time zero to 72 hours post dose, calculated by linear-linear trapezoidal summation. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite Aprocitentan |
t1/2 is defined as apparent terminal elimination half-life of macitentan and its metabolite aprocitentan. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and its Metabolite Aprocitentan |
Lambda(z) is defined as apparent terminal elimination rate constant of macitentan and its metabolite aprocitentan, estimated by linear regression using the terminal log-linear phase of the log transformed concentration versus time curve. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Total Apparent Oral Clearance (CL/F) of Macitentan |
CL/F of macitentan is defined as total apparent oral clearance, calculated as dose/AUC (0-infinity). |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Apparent Volume of Distribution (Vdz/F) of Macitentan |
Vdz/F of macitentan is defined as apparent volume of distribution, calculated as dose/(Lambda[z]*AUC [0-infinity]). |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan |
Cmax is defined as maximum observed plasma analyte concentration of metabolite aprocitentan. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Time of the Last Quantifiable Concentration of Aprocitentan (AUC[0-last]) |
AUC(0-last) of metabolite Aprocitentan 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. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Area Under the Plasma Analyte Concentration-Time Curve of Aprocitentan from Time Zero to Infinity (AUC[0-infinity]) |
AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve of metabolite aprocitentan from time zero to infinite time. |
Predose, up to 336 hours post dose (up to Day 15) |
|
Secondary |
Number of Participants with Serious Adverse Events (SAEs) |
Number of Participants with Serious Adverse Events (SAEs) will be reported 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. |
Up to 13 weeks |
|
Secondary |
Number of Participants with Adverse Events (AEs) |
Number of participants with AEs will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. |
Up to 13 weeks |
|
Secondary |
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. |
Up to Day 15 |
|
Secondary |
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. |
Up to Day 15 |
|
Secondary |
Number of Participants with Abnormalities in Electrocardiograms (ECGs) |
Number of participants with abnormalities in ECGs will be reported. |
Up to Day 15 |
|
Secondary |
Number of Participants with Abnormalities in Clinical Laboratory Tests |
Number of participants with abnormalities in clinical laboratory tests (including serum chemistry, hematology, and urinalysis) will be reported. |
Up to Day 15 |
|