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 and up to 216 hours post dose (Up to Day 10) |
|
Primary |
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) |
|
Primary |
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 |
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. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Predose up to 72 hours post dose |
|
Secondary |
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). |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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). |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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]). |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
Maximum Observed Plasma Analyte Concentration (Cmax) of Metabolite ACT-132577 |
Cmax is defined as maximum observed plasma analyte concentration of metabolite ACT-132577. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Predose and up to 216 hours post dose (Up to Day 10) |
|
Secondary |
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. |
Up to Week 10 |
|
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 10 of each treatment period (Up to 7 weeks) |
|
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 10 of each treatment period (Up to 7 weeks) |
|
Secondary |
Number of Participants with Abnormalities in Electrocardiograms (ECGs) |
Number of participants with abnormalities in ECGs will be reported. |
Up to Day 10 of each treatment period (Up to 7 weeks) |
|
Secondary |
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. |
Up to Day 10 of each treatment period (Up to 7 weeks) |
|