Pulmonary Arterial Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate the effect of macitentan on hemodynamic measures at Week 24 in pediatric populations.
Interventions
DRUGMacitentan
Macitentan will be administered orally as a tablet.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 15 Years
Healthy volunteers
No
Inclusion criteria
* Pulmonary arterial hypertension (PAH) belonging to the nice 2013 updated classification group 1 * PAH diagnosis confirmed by historical right heart catheterization where in the absence of pulmonary vein obstruction and/or significant lung disease pulmonary artery wedge pressure (PAWP) can be replaced by left atrium pressure (LAP) or left ventricular end diastolic pressure (LVEDP) (in absence of mitral stenosis) assessed by heart catheterization * World Health Organization (WHO) functional class (FC) I to IV * PAH-specific treatment-naïve participants or participants on PAH-specific treatment * A female of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) test at screening and a negative urine pregnancy test at the first administration of study intervention * A female participant must not get pregnant and must agree not to donate eggs during the study and for a period of up to 4 weeks following the end of study
Exclusion criteria
* Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn * Participants with the following diseases: pulmonary vein stenosis; bronchopulmonary dysplasia * Severe hepatic impairment, example, Child-Pugh Class C, at screening * Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 weeks after the last dose of study intervention * Known allergies, hypersensitivity, or intolerance to macitentan or its excipients * Participant with PAH associated with open shunts, with congenital cardiac abnormalities such as univentricular heart, with pulmonary hypertension due to lung disease, and renal dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI) | Baseline (Day 1), Week 24 | PVRI fold change at Week 24 was calculated as 100\*(PVRI at Week 24 divided by PVRI at baseline). PVR was determined by right heart catheterization. |
| Change From Baseline in Hematology Parameter: Neutrophils Band Form (NBF) | Baseline (Day 1), Weeks 8, 16, 20, 40, 52 | Change from baseline in hematology parameters: NBF was reported. Data for each parameters was planned to be reported at specified timepoints only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: PVR was reported. PVR is calculated as: PVR= (Mean pulmonary artery pressure \[mPAP\]-Pulmonary artery wedge pressure \[PAWP)/ Cardiac output \[CO\]. |
| Change From Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: mRAP was reported. |
| Change From Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Arterial Pressure (mPAP) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: mPAP was reported. mPAP is calculated as: 2\*diastolic pulmonary arterial pressure (dPAP) + systolic pulmonary arterial pressure (sPAP)/3. |
| Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: CI was reported. CI was calculated as: CO/Body surface area (BSA). |
| Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: CO was reported. |
| Change From Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR) | Baseline (Day 1), Week 24 | Change from baseline to Week 24 in hemodynamic variable: TPR was reported. TPR was calculated as: (mPAP/CO)\*80. |
| Percent Change From Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2]) | Baseline (Day 1), Week 24 | Percent change from baseline to Week 24 in hemodynamic variable: SvO(2) was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline (Day 1) up to Week 56 | Number of participants with TEAEs was reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs are defined as any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | From Baseline (Day 1) up to Week 56 | Number of participants with TESAEs was reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TESAEs are defined as any SAE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days. |
| Number of Participants With AEs Leading to Premature Discontinuation of Study Drug | From Baseline (Day 1) up to Week 52 | Number of participants with AEs leading to premature discontinuation of study drug was reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Number of Participants With TEAEs of Special Interest | From Baseline (Day 1) up to Week 56 | Number of participants with TEAEs of special interest was reported. It included anemia/decreased hemoglobin level, oedema/fluid retention, hepatic impairment and hypotension. TEAEs are defined as any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days. |
| Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values | Weeks 20, 40, 52 | Number of participants with postbaseline markedly abnormal hematology laboratory values was reported. It included Hematocrit:\<0.28% of blood cells (\<0.32M\[%\]), Hemoglobin: \< 100 grams per liter (g/L), Leukocytes: \<3.0 10\^9 cells per Liter (L), and Leukocytes: \<3.0 10\^9 cells/L. Abnormality was judged at the discretion of investigator. Data is reported for categories where at least one participant had abnormality. |
| Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Potassium and Calcium | Week 4 | Number of participants with postbaseline markedly abnormal clinical chemistry laboratory values was reported. It included Potassium: \>6.0 millimoles per liter (mmol/L) and Calcium: \<1.75 mmol/L. Abnormality was judged at the discretion of investigator. Data is reported for categories where at least one participant had abnormality. |
| Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Alkaline Phosphatase (ALP) | Week 28 | Number of participants with postbaseline markedly abnormal clinical chemistry laboratory values (ALP) was reported. It included Alkaline Phosphatase (ALP): \> 2.5 \* Upper Limit of Normal (ULN). Abnormality was judged at the discretion of investigator. Participants were assessed at Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52. Data is reported for categories where at least one participant had abnormality at any time point: Weeks 20, 40, and 52 reported. |
| Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, and Basophils | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in hematology parameters: platelets, leukocytes, lymphocytes, monocytes, eosinophils, and basophils was reported. Data for each parameters was planned to be reported at specified timepoints only. |
| Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in hematology parameter: hematocrit was reported. |
| Change From Baseline in Hematology Parameters: Hemoglobin | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in hematology parameter: hemoglobin was reported. |
| Change From Baseline in Hematology Parameter: Erythrocytes | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in hematology parameter: erythrocytes was reported. |
| Change From Baseline in Chemistry Parameters: Sodium, Potassium, Urea Nitrogen, Glucose, and Calcium | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in chemistry parameters: sodium, potassium, urea nitrogen, glucose, and calcium was reported. |
| Change From Baseline in Chemistry Parameters: Creatinine (Jaffe Reaction), Bilirubin, and Direct Bilirubin | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in chemistry parameters: Creatinine, bilirubin, and direct bilirubin was reported. |
| Change From Baseline in Chemistry Parameter: Creatinine Clearance | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in chemistry parameter: creatinine clearance was reported. |
| Change From Baseline in Chemistry Parameters: Glomerular Filtration Rate (GFR) From Cystatin C Adjusted for Body Surface Area (BSA) | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in chemistry parameter: GFR from Cystatin C Adjusted for BSA was reported. |
| Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in chemistry parameters: AST, ALT, and ALP was reported. |
| Change From Baseline in Vital Signs: Blood Pressure | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in vital signs: blood pressure was reported. It included systolic blood pressure (SBP) and diastolic blood pressure (DBP). |
| Change From Baseline in Vital Signs: Pulse Rate | Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Change from baseline in vital signs: pulse rate was reported. |
| Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline in ECG: heart rate was reported. |
| Change From Baseline in Electrocardiogram (ECG) Parameter: PR, QRS, QT, Corrected QT Interval-Bazett's Formula (QTcB), and Corrected QT Interval-Fridericia's Formula (QTcF) | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline in ECG: PR, QRS, QT, QTcB, and QTcF intervals was reported. |
| Plasma Concentration of Macitentan: Participants >=2 Years Old | Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12 | Plasma concentration of macitentan was reported. |
| Plasma Concentration of Aprocitentan (Active Metabolite): Participants >=2 Years Old | Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12 | Plasma concentration of aprocitentan was reported. |
| Plasma Concentration of Macitentan: Participants <2 Years Old | Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8 | Plasma concentration of macitentan was reported. |
| Plasma Concentration of Aprocitentan (Active Metabolite): Participants <2 Years Old | Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8 | Plasma concentration of aprocitentan was reported. |
| Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in World Health Organization (WHO) Functional Class (FC) | Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 | WHO-FC for participants with pulmonary arterial hypertension (PAH) ranges: Class I (no limitation in physical activity, ordinary physical activity did not cause undue dyspnea or fatigue, chest pain or near syncope), Class II (slight limitation of physical activity, comfortable at rest, ordinary physical activity caused undue dyspnea or fatigue, chest pain, or near syncope), Class III (marked limitation of physical activity, comfortable at rest, less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope) and Class IV (cannot perform a physical activity without any symptoms, signs of right heart failure, dyspnea and/or fatigue may be present even at rest, discomfort is increased by any physical activity). Participants who improve in WHO FC are reported below. Improvement was defined as reduction in FC. |
| Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama Functional Class (FC) | Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52 | Panama FC for PAH ranges: Class I (asymptomatic, growing normally, attending nursery/school regularly, no limitation of physical activity, playing sports with his/her classmates), Class II (slight limitation of physical activity, unduly dyspnoeic and fatigued when playing with his/her classmates, comfortable at rest, grow along own centiles, nursery/school attendance 75% normal, no chest pain), Class IIIa (marked limitation of physical activity, no attempt at sports, comfortable at rest, less than ordinary activity (example: dressing) causes undue dyspnea, fatigue, syncope and/or presyncope or chest pain, nursery/schooling compromised \<50% normal attendance), Class IIIb (growth compromised, poor appetite, supplemental feeding, same as class IIIa) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). Participants who improve in Panama FC are reported below. Improvement was defined as reduction in Panama FC. |
| Change From Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) | Baseline (Day 1), Weeks 24 and 52 | Change from baseline to Weeks 24 and 52 in 6MWD as measured by 6MWT was reported. 6MWD was the distance that a participant could walk in 6 minutes. Rest periods were allowed if the participant could no longer continue. If the participant need to rest, he/she may pause, lean against the wall and continue walking whenever he/she feels able. The timer continued to run even if the participant stopped to rest. |
| Change From Baseline to Weeks 12, 24, 28, 40, and 52 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Baseline (Day 1), Week 12, 24, 28, 40, and 52 | Change from baseline to Weeks 12, 24, 28, 40, and 52 in NT-proBNP was reported. |
| Change From Baseline to Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE) | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in TAPSE was reported. It was calculated as: original TAPSE value/body surface area (BSA). TAPSE was a dimension used to evaluate Right Ventricle (RV) longitudinal systolic function; it measured the extent of systolic motion of the lateral portion of the tricuspid ring towards the apex. |
| Change From Baseline to Week 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI) | Baseline (Day 1), Weeks 12, 24 and 52 | Change from baseline to Weeks 12, 24, and 52 in LVEI was reported. It included diastolic (D) LVEI and systolic (S) LVEI. Left ventricular (LV) internal diameters were measured using the parasternal short axis view at the level of the papillary muscles: D1: LV internal diameter perpendicular to interventricular septum at end-diastole; D2: LV internal diameter parallel to interventricular septum, and at right angle from D1, at end-diastole; S1: LV internal diameter perpendicular to interventricular septum at end-systole; S2: LV internal diameter parallel to interventricular septum, and at a right angle from S1, at end-systole. The LVEI was a ratio that was calculated by sponsor as: LVEI diastole = D2/D1; LVEI systole = S2/S1. |
| Change From Baseline to Week 12, 24, and 52 in Quality of Life (QoL) as Assessed by Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales Short Form (SF-15) | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in QoL as assessed by PedsQL 4.0 generic core scales SF-15 was reported. The PedsQL 4.0 questionnaire generic core scales score SF-15 assessed general physical, emotional, social and school functioning on a 5-point Likert scale from 0 to 4 with 0= if it is never a problem, 1= if it is almost never a problem, 2= if it is sometime a problem, 3= if it is often a problem, 4 if it is almost always a problem. Scores were transformed on a scale from 0 to 100. Higher scores indicated better health related QoL. The QoL questionnaire was completed by parent(s)/caregiver(s) and by participants. |
| Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Number of Hours of Daytime Activity | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: number of hours of daytime activity was reported. |
| Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Count Per Minute of Daily Activity | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: mean count per minute of daily activity was reported. |
| Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Light Physical Activity | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: mean daily time spent in light physical activity was reported. |
| Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Moderate to Vigorous Physical Activity | Baseline (Day 1), Weeks 12, 24, and 52 | Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: mean daily time spent in moderate to vigorous physical activity was reported. |
| Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index (BDI) | Baseline (Day 1), Weeks 24 and 52 | Change from baseline to Weeks 24 and 52 in BDI was reported. BDI was a 10-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores ranged from 0 (no shortness of breath) to 10 (worst shortness of breath you have ever had). Higher score indicated worse outcome. |
Countries
Japan
Contacts
STUDY_DIRECTORJanssen Pharmaceutical K.K. Clinical Trial
Janssen Pharmaceutical K.K.
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Macitentan Participants aged between 3 months and 14 years, inclusive with pulmonary arterial hypertension (PAH) received macitentan 1 milligram (mg) or 2.5 mg tablets orally once daily based on age and body weight. Participants aged greater than or equal to (\>=) 3 months to less than (\<) 6 months received daily dose of macitentan 1 mg, \>=6 months to \<2 years received daily dose of macitentan 2.5 mg. For participants above 2 years (inclusive) of age, daily doses of macitentan were 3.5 mg (\<15 kilograms \[kg\] body weight \[BW\]), 5 mg (\>=15 kg to \<25 kg BW), 7.5 mg (\>=25 kg to \<50 kg BW), and 10 mg (\>=50 kg BW). Treatment was administered from Day 1 to Week 52 followed by 30 days follow up after end of treatment. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Macitentan |
|---|---|
| Age, Customized < 2 years | 2 Participants |
| Age, Customized >= 2 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment Japan | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 2 / 7 |
Outcome results
Primary
Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI)
PVRI fold change at Week 24 was calculated as 100\*(PVRI at Week 24 divided by PVRI at baseline). PVR was determined by right heart catheterization.
Time frame: Baseline (Day 1), Week 24
Population: Efficacy analysis set included all participants who were administered at least 1 dose of macitentan.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Macitentan | Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI) | 59.43 Fold change (percentage) | Geometric Coefficient of Variation 75.1 |
Secondary
Change From Baseline at Week 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI)
Time frame: Baseline (Day 1), Weeks 12, 24 and 52
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Cardiac Index (CI)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Cardiac Output (CO)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Mean Pulmonary Arterial Pressure (mPAP)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Mixed Venous Oxygen Saturation (SvO2)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Pulmonary Vascular Resistance (PVR)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Week 24 in Hemodynamic Variables: Total Pulmonary Resistance (TPR)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline at Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline in Body Weight
Time frame: From baseline (Day 1) up to Week 56
Secondary
Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, and Alkaline Phosphatase
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin, and Direct Bilirubin
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Chemistry Parameters: Creatinine Clearance
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Chemistry Parameters: GFR From Cystatin C Adjusted for BSA
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Chemistry Parameters: Sodium, Potassium, Urea Nitrogen, Glucose, and Calcium
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameter: PR, QRS, QT, Corrected QT Interval-Bazett's Formula (QTcB), and Corrected QT Interval-Fridericia's Formula (QTcF)
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline in Height
Time frame: From baseline (Day 1) up to Week 56
Secondary
Change From Baseline in Hematology Parameters: Erythrocytes
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Hematology Parameters: Hematocrit
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Hematology Parameters: Hemoglobin
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils Band Form, Lymphocytes, Monocytes, Eosinophils, and Basophils
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Mean Right Atrial Pressure (mRAP)
Time frame: Baseline (Day 1), Week 24
Secondary
Change From Baseline in Vital Signs: Blood Pressure
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline in Vital Signs: Pulse Rate
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Change From Baseline to Week 12, 24, 28, 40, and 52 in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline (Day 1), Week 12, 24, 28, 40, and 52
Secondary
Change From Baseline to Week 12, 24, and 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales Short Form (SF-15)
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index
Time frame: Baseline (Day 1), Weeks 24 and 52
Secondary
Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Count Per Minute of Daily Activity
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Light Physical Activity
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Moderate to Vigorous Physical Activity
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Number of Hours of Daytime Activity
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Secondary
Change From Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)
Time frame: Baseline (Day 1), Weeks 24 and 52
Secondary
Number of Participants With AEs Leading to Premature Discontinuation of Macitentan
Time frame: From Baseline (Day 1) up to Week 52
Secondary
Number of Participants With AEs of Special Interest
Time frame: From Baseline (Day 1) up to Week 56
Secondary
Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama FC
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in World Health Organization (WHO) Functional Class (FC)
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From Baseline (Day 1) up to Week 56
Secondary
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From Baseline (Day 1) up to Week 56
Secondary
Plasma Concentration of Aprocitentan: Participants <2 Years Old
Time frame: Baseline (Day 1) up to Week 8
Secondary
Plasma Concentration of Aprocitentan: Participants >=2 Years Old
Time frame: Baseline (Day 1) up to Week 12
Secondary
Plasma Concentration of Macitentan: Participants <2 Years Old
Time frame: Baseline (Day 1) up to Week 8
Secondary
Plasma Concentration of Macitentan: Participants >=2 Years Old
Time frame: Baseline (Day 1) up to Week 12