A Phase 3 interventional study of Macitentan in Pulmonary Arterial Hypertension, sponsored by Janssen Pharmaceutical K.K.. Completed at 11 sites in Japan. Open to participants aged 3 Months to 15 Years. Per ClinicalTrials.gov, last updated 2026-05-07.
Sponsored by Janssen Pharmaceutical K.K. (part of Johnson & Johnson) · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the effect of macitentan on hemodynamic measures at Week 24 in pediatric populations.
699 studies on the registry are indexed under Pulmonary Arterial Hypertension; 140 are open to participants now.
This study's enrollment of 7 is below the median of 40 across 477 interventional studies indexed under Pulmonary Arterial Hypertension.
Browse Pulmonary Arterial Hypertension studies →Janssen Pharmaceutical K.K. is the lead sponsor of 126 studies on the registry; none are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 7 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive oral dose of macitentan based on age and weight through Week 52.
Drug: Macitentan
Macitentan will be administered orally as a tablet.
Also known as: OPSUMIT, ZEPENDO
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
Change From Baseline in Hematology Parameter: Neutrophils Band Form (NBF)
Change from baseline in hematology parameters: NBF was reported. Data for each parameters was planned to be reported at specified timepoints only.
Time frame: Baseline (Day 1), Weeks 8, 16, 20, 40, 52
Change From Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR)
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 \[CO\].
Time frame: Baseline (Day 1), Week 24
Change From Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP)
Change from baseline to Week 24 in hemodynamic variable: mRAP was reported.
Time frame: Baseline (Day 1), Week 24
Change From Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Arterial Pressure (mPAP)
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.
Time frame: Baseline (Day 1), Week 24
Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI)
Change from baseline to Week 24 in hemodynamic variable: CI was reported. CI was calculated as: CO/Body surface area (BSA).
Time frame: Baseline (Day 1), Week 24
Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO)
Change from baseline to Week 24 in hemodynamic variable: CO was reported.
Time frame: Baseline (Day 1), Week 24
Change From Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR)
Change from baseline to Week 24 in hemodynamic variable: TPR was reported. TPR was calculated as: (mPAP/CO)\*80.
Time frame: Baseline (Day 1), Week 24
Percent Change From Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2])
Percent change from baseline to Week 24 in hemodynamic variable: SvO(2) was reported.
Time frame: Baseline (Day 1), Week 24
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)
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.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52
Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama Functional Class (FC)
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.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)
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.
Time frame: Baseline (Day 1), Weeks 24 and 52
Change From Baseline to Weeks 12, 24, 28, 40, and 52 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Change from baseline to Weeks 12, 24, 28, 40, and 52 in NT-proBNP was reported.
Time frame: Baseline (Day 1), Week 12, 24, 28, 40, and 52
Change From Baseline to Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE)
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.
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Change From Baseline to Week 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI)
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.
Time frame: Baseline (Day 1), Weeks 12, 24 and 52
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)
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.
Time frame: 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
Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: number of hours of daytime activity was reported.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index (BDI)
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.
Time frame: Baseline (Day 1), Weeks 24 and 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: From Baseline (Day 1) up to Week 56
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
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.
Time frame: From Baseline (Day 1) up to Week 56
Number of Participants With AEs Leading to Premature Discontinuation of Study Drug
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.
Time frame: From Baseline (Day 1) up to Week 52
Number of Participants With TEAEs of Special Interest
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.
Time frame: From Baseline (Day 1) up to Week 56
Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values
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.
Time frame: Weeks 20, 40, 52
Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Potassium and Calcium
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.
Time frame: Week 4
Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Alkaline Phosphatase (ALP)
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.
Time frame: Week 28
Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, and Basophils
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.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Hematology Parameter: Hematocrit
Change from baseline in hematology parameter: hematocrit was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Hematology Parameters: Hemoglobin
Change from baseline in hematology parameter: hemoglobin was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Hematology Parameter: Erythrocytes
Change from baseline in hematology parameter: erythrocytes was reported.
Time frame: 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
Change from baseline in chemistry parameters: sodium, potassium, urea nitrogen, glucose, and calcium was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Chemistry Parameters: Creatinine (Jaffe Reaction), Bilirubin, and Direct Bilirubin
Change from baseline in chemistry parameters: Creatinine, bilirubin, and direct bilirubin was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Chemistry Parameter: Creatinine Clearance
Change from baseline in chemistry parameter: creatinine clearance was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Chemistry Parameters: Glomerular Filtration Rate (GFR) From Cystatin C Adjusted for Body Surface Area (BSA)
Change from baseline in chemistry parameter: GFR from Cystatin C Adjusted for BSA was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP)
Change from baseline in chemistry parameters: AST, ALT, and ALP was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Vital Signs: Blood Pressure
Change from baseline in vital signs: blood pressure was reported. It included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Vital Signs: Pulse Rate
Change from baseline in vital signs: pulse rate was reported.
Time frame: Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
Change from baseline in ECG: heart rate was reported.
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
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)
Change from baseline in ECG: PR, QRS, QT, QTcB, and QTcF intervals was reported.
Time frame: Baseline (Day 1), Weeks 12, 24, and 52
Plasma Concentration of Macitentan: Participants >=2 Years Old
Plasma concentration of macitentan was reported.
Time frame: Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12
Plasma Concentration of Aprocitentan (Active Metabolite): Participants >=2 Years Old
Plasma concentration of aprocitentan was reported.
Time frame: Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12
Plasma Concentration of Macitentan: Participants <2 Years Old
Plasma concentration of macitentan was reported.
Time frame: Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8
Plasma Concentration of Aprocitentan (Active Metabolite): Participants <2 Years Old
Plasma concentration of aprocitentan was reported.
Time frame: Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8
| Milestone | Macitentan |
|---|---|
| Started | 7 |
| Completed | 7 |
| Not completed | 0 |
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.
| Fold change (percentage) | Macitentan |
|---|---|
| Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI) | 59.43 ± 75.1 |
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 \[CO\].
| wood units (WU) | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR) | -3.734 ± 4.4971 |
Change from baseline to Week 24 in hemodynamic variable: mRAP was reported.
| Millimeters of mercury (mmHg) | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP) | -2.9 ± 8.57 |
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.
| millimeters of mercury (mmHg) | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Arterial Pressure (mPAP) | -8.0 ± 12.62 |
Change from baseline to Week 24 in hemodynamic variable: CI was reported. CI was calculated as: CO/Body surface area (BSA).
| Liters/minute/meter square (L/min/m^2) | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI) | -0.03 ± 1.019 |
Change from baseline to Week 24 in hemodynamic variable: CO was reported.
| Liters per minute (L/min) | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO) | 0.07 ± 0.743 |
Change from baseline to Week 24 in hemodynamic variable: TPR was reported. TPR was calculated as: (mPAP/CO)\*80.
| Dynes*second/centimeter^5 | Macitentan |
|---|---|
| Change From Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR) | -243.0 ± 410.13 |
Percent change from baseline to Week 24 in hemodynamic variable: SvO(2) was reported.
| Percent change | Macitentan |
|---|---|
| Percent Change From Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2]) | -2.9 ± 9.37 |
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.
| Participants | Macitentan |
|---|---|
| Week 4 | 0 |
| Week 8 | 0 |
| Week 12 | 0 |
| Week 16 | 0 |
| Week 20 | 0 |
| Week 24 | 0 |
| Week 28 | 0 |
| Week 40 | 0 |
| Week 52 | 0 |
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.
| Participants | Macitentan |
|---|---|
| Week 4 | 0 |
| Week 8 | 0 |
| Week 12 | 0 |
| Week 16 | 0 |
| Week 20 | 0 |
| Week 24 | 0 |
| Week 28 | 0 |
| Week 40 | 0 |
| Week 52 | 0 |
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.
| Meters | Macitentan |
|---|---|
| Week 24 | 4.897 ± 43.6657 |
| Week 52 | 24.710 ± 105.6559 |
Change from baseline to Weeks 12, 24, 28, 40, and 52 in NT-proBNP was reported.
| Picograms per milliliter (pg/mL) | Macitentan |
|---|---|
| Week 12 | 6.5911 ± 18.85065 |
| Week 24 | -3.7423 ± 7.79983 |
| Week 28 | -3.1663 ± 20.38136 |
| Week 40 | -5.7146 ± 14.23745 |
| Week 52 | -0.2360 ± 10.15074 |
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.
| Millimeters per meter square (mm/m^2) | Macitentan |
|---|---|
| Week 12 | 2.766 ± 1.6763 |
| Week 24 | 1.873 ± 1.0379 |
| Week 52 | 2.412 ± 1.3666 |
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.
| Ratio | Macitentan |
|---|---|
| Diastolic: Week 12 | 0.116 ± 0.1241 |
| Diastolic: Week 24 | 0.125 ± 0.1491 |
| Diastolic: Week 52 | 0.128 ± 0.0762 |
| Systolic: Week 12 | 0.237 ± 0.1519 |
| Systolic: Week 24 | 0.229 ± 0.2396 |
| Systolic: Week 52 | 0.237 ± 0.1225 |
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.
| Score on a scale | Macitentan |
|---|---|
| Total score parents/caregiver report: Week 12 | 8.905 ± 6.1274 |
| Total score parents/caregiver report: Week 24 | 8.190 ± 11.3259 |
| Total score parents/caregiver report: Week 52 | 15.810 ± 7.8366 |
| Total score - participant report: Week 12 | 8.889 ± 3.4694 |
| Total score - participant report: Week 24 | -2.222 ± 17.8211 |
| Total score - participant report: Week 52 | 16.667 ± 20.2759 |
Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: number of hours of daytime activity was reported.
| Hours | Macitentan |
|---|---|
| Week 12 | -0.929 ± 0.9741 |
| Week 24 | -0.280 ± 1.3553 |
| Week 52 | 0.144 ± 0.4985 |
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.
| Counts per minutes per day | Macitentan |
|---|---|
| Week 12 | 73.946 ± 205.4249 |
| Week 24 | 112.733 ± 219.3168 |
| Week 52 | 125.427 ± 157.5824 |
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.
| minutes per day | Macitentan |
|---|---|
| Week 12 | 1.600 ± 46.5857 |
| Week 24 | 35.159 ± 92.2011 |
| Week 52 | 38.852 ± 57.1818 |
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.
| minutes per day | Macitentan |
|---|---|
| Week 12 | 0.032 ± 0.4424 |
| Week 24 | 0.169 ± 0.6058 |
| Week 52 | 0.493 ± 1.5023 |
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.
| Score on a scale | Macitentan |
|---|---|
| Week 24 | 0.00 ± 0.000 |
| Week 52 | -1.17 ± 0.764 |
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.
| Participants | Macitentan |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 |
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.
| Participants | Macitentan |
|---|---|
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 2 |
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.
| Participants | Macitentan |
|---|---|
| Number of Participants With AEs Leading to Premature Discontinuation of Study Drug | 0 |
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.
| Participants | Macitentan |
|---|---|
| Number of Participants With TEAEs of Special Interest | 1 |
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.
| Participants | Macitentan |
|---|---|
| Hematocrit:<0.28% of blood cells(<0.32M[%]): Week 20 | 1 |
| Hemoglobin: < 100 g/L: Week 20 | 1 |
| Leukocytes: <3.0 10^9 cells/ L: Week 40 | 1 |
| Leukocytes: <3.0 10^9 cells/L: Week 52 | 1 |
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.
| Participants | Macitentan |
|---|---|
| Potassium: >6.0 mmol/L: Week 4 | 1 |
| Calcium: <1.75 mmol/L: Week 4 | 1 |
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.
| Participants | Macitentan |
|---|---|
| Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Alkaline Phosphatase (ALP) | 1 |
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.
| 10^9 cells per liter (10^9 cells/L) | Macitentan |
|---|---|
| Platelets: Week 4 | -20.4 ± 31.90 |
| Platelets: Week 8 | -47.9 ± 42.32 |
| Platelets: Week 12 | -23.3 ± 70.86 |
| Platelets: Week 16 | -41.3 ± 53.21 |
| Platelets: Week 20 | -42.4 ± 86.32 |
| Platelets: Week 24 | -42.6 ± 77.72 |
| Platelets: Week 28 | -22.0 ± 59.29 |
| Platelets: Week 40 | -40.3 ± 106.10 |
| Platelets: Week 52 | -56.7 ± 92.37 |
| Leukocytes: Week 4 | 0.031 ± 3.7398 |
| Leukocytes: Week 8 | 0.549 ± 3.4816 |
| Leukocytes: Week 12 | -0.131 ± 2.3574 |
| Leukocytes: Week 16 | -0.321 ± 1.5230 |
| Leukocytes: Week 20 | -1.256 ± 3.7745 |
| Leukocytes: Week 24 | 0.214 ± 3.6431 |
| Leukocytes: Week 28 | -0.347 ± 2.8012 |
| Leukocytes: Week 40 | -1.660 ± 3.0486 |
| Leukocytes: Week 52 | -0.541 ± 2.7583 |
| Lymphocytes: Week 4 | -0.144 ± 0.4446 |
| Lymphocytes: Week 8 | -0.240 ± 0.5289 |
| Lymphocytes: Week 12 | -0.451 ± 0.3151 |
| Lymphocytes: Week 16 | -0.294 ± 0.1784 |
| Lymphocytes: Week 20 | -0.286 ± 0.8204 |
| Lymphocytes: Week 24 | -0.224 ± 0.5638 |
| Lymphocytes: Week 28 | -0.255 ± 0.5392 |
| Lymphocytes: Week 40 | -0.649 ± 0.5258 |
| Lymphocytes: Week 52 | -0.411 ± 0.5227 |
| Monocytes: Week 4 | -0.029 ± 0.0807 |
| Monocytes: Week 8 | 0.070 ± 0.2063 |
| Monocytes: Week 12 | 0.033 ± 0.0925 |
| Monocytes: Week 16 | -0.046 ± 0.0382 |
| Monocytes: Week 20 | -0.081 ± 0.0928 |
| Monocytes: Week 24 | 0.017 ± 0.1042 |
| Monocytes: Week 28 | -0.052 ± 0.0884 |
| Monocytes: Week 40 | -0.103 ± 0.0911 |
| Monocytes: Week 52 | -0.086 ± 0.0988 |
| Eosinophils: Week 4 | -0.011 ± 0.0811 |
| Eosinophils: Week 8 | -0.009 ± 0.0795 |
| Eosinophils: Week 12 | 0.066 ± 0.1153 |
| Eosinophils: Week 16 | 0.030 ± 0.1606 |
| Eosinophils: Week 20 | 0.086 ± 0.1752 |
| Eosinophils: Week 24 | -0.016 ± 0.1066 |
| Eosinophils: Week 28 | -0.040 ± 0.1119 |
| Eosinophils: Week 40 | 0.000 ± 0.0693 |
| Eosinophils: Week 52 | 0.220 ± 0.6577 |
| Basophils: Week 4 | 0.016 ± 0.0162 |
| Basophils: Week 8 | 0.009 ± 0.0273 |
| Basophils: Week 12 | 0.016 ± 0.0270 |
| Basophils: Week 16 | 0.016 ± 0.0465 |
| Basophils: Week 20 | 0.000 ± 0.0183 |
| Basophils: Week 24 | 0.016 ± 0.0257 |
| Basophils: Week 28 | 0.008 ± 0.0256 |
| Basophils: Week 40 | -0.004 ± 0.0276 |
| Basophils: Week 52 | 0.053 ± 0.1073 |
Change from baseline in hematology parameters: NBF was reported. Data for each parameters was planned to be reported at specified timepoints only.
| 10^9 cells per liter (10^9 cells/L) | Macitentan |
|---|---|
| Week 8 | 0.120 ± NA |
| Week 16 | 0.480 ± NA |
| Week 20 | 0.055 ± 0.1485 |
| Week 40 | -0.050 ± NA |
| Week 52 | -0.030 ± NA |
Change from baseline in hematology parameter: hematocrit was reported.
| Percentage of blood cells | Macitentan |
|---|---|
| Week 4 | 0.009 ± 0.0204 |
| Week 8 | 0.016 ± 0.0223 |
| Week 12 | 0.004 ± 0.0230 |
| Week 16 | -0.006 ± 0.0299 |
| Week 20 | -0.004 ± 0.0282 |
| Week 24 | 0.006 ± 0.0355 |
| Week 28 | 0.010 ± 0.0237 |
| Week 40 | 0.010 ± 0.0216 |
| Week 52 | 0.010 ± 0.0404 |
Change from baseline in hematology parameter: hemoglobin was reported.
| grams per liter (g/L) | Macitentan |
|---|---|
| Week 4 | 1.9 ± 9.12 |
| Week 8 | 2.3 ± 8.28 |
| Week 12 | -0.1 ± 9.60 |
| Week 16 | -3.0 ± 9.35 |
| Week 20 | -4.1 ± 5.84 |
| Week 24 | -0.3 ± 9.81 |
| Week 28 | -2.7 ± 8.71 |
| Week 40 | 0.1 ± 8.91 |
| Week 52 | 0.7 ± 11.84 |
Change from baseline in hematology parameter: erythrocytes was reported.
| 10^12 cells per liter (10^12 cells/L) | Macitentan |
|---|---|
| Week 4 | 0.03 ± 0.236 |
| Week 8 | 0.13 ± 0.309 |
| Week 12 | 0.04 ± 0.336 |
| Week 16 | -0.07 ± 0.269 |
| Week 20 | -0.06 ± 0.230 |
| Week 24 | 0.04 ± 0.299 |
| Week 28 | 0.07 ± 0.266 |
| Week 40 | 0.07 ± 0.335 |
| Week 52 | 0.04 ± 0.412 |
Change from baseline in chemistry parameters: sodium, potassium, urea nitrogen, glucose, and calcium was reported.
| millimoles per liter (mmol/L) | Macitentan |
|---|---|
| Sodium: Week 4 | -0.1 ± 3.85 |
| Sodium: Week 8 | 0.1 ± 1.57 |
| Sodium: Week 12 | 0.2 ± 1.17 |
| Sodium: Week 16 | -0.7 ± 1.98 |
| Sodium: Week 20 | -0.1 ± 2.34 |
| Sodium: Week 24 | 0.3 ± 2.98 |
| Sodium: Week 28 | 1.5 ± 1.87 |
| Sodium: Week 40 | -0.1 ± 2.04 |
| Sodium: Week 52 | -0.7 ± 2.43 |
| Potassium: Week 4 | 0.46 ± 1.137 |
| Potassium: Week 8 | 0.03 ± 0.330 |
| Potassium: Week 12 | 0.10 ± 0.494 |
| Potassium: Week 16 | -0.09 ± 0.234 |
| Potassium: Week 20 | 0.03 ± 0.315 |
| Potassium: Week 24 | -0.09 ± 0.261 |
| Potassium: Week 28 | -0.07 ± 0.186 |
| Potassium: Week 40 | 0.07 ± 0.298 |
| Potassium: Week 52 | 0.04 ± 0.336 |
| Urea Nitrogen: Week 4 | -0.0510 ± 1.32665 |
| Urea Nitrogen: Week 8 | -0.3060 ± 1.32665 |
| Urea Nitrogen: Week 12 | 0.0000 ± 1.39184 |
| Urea Nitrogen: Week 16 | 0.3060 ± 1.19170 |
| Urea Nitrogen: Week 20 | -0.8160 ± 1.10448 |
| Urea Nitrogen: Week 24 | -0.1020 ± 1.14229 |
| Urea Nitrogen: Week 28 | -0.3570 ± 0.98418 |
| Urea Nitrogen: Week 40 | -0.8160 ± 1.40875 |
| Urea Nitrogen: Week 52 | -0.3060 ± 1.84847 |
| Glucose: Week 4 | 0.34099 ± 0.601656 |
| Glucose: Week 8 | 0.22204 ± 0.652101 |
| Glucose: Week 12 | 0.05548 ± 0.641615 |
| Glucose: Week 16 | 0.35684 ± 0.503536 |
| Glucose: Week 20 | 0.47580 ± 0.527417 |
| Glucose: Week 24 | 0.60266 ± 0.730401 |
| Glucose: Week 28 | 0.60133 ± 0.933768 |
| Glucose: Week 40 | 0.39649 ± 0.628362 |
| Glucose: Week 52 | 0.00791 ± 0.554573 |
| Calcium: Week 4 | -0.09980 ± 0.293456 |
| Calcium: Week 8 | -0.00357 ± 0.098172 |
| Calcium: Week 12 | -0.04158 ± 0.068184 |
| Calcium: Week 16 | -0.04634 ± 0.124293 |
| Calcium: Week 20 | -0.07486 ± 0.097716 |
| Calcium: Week 24 | -0.03564 ± 0.097564 |
| Calcium: Week 28 | -0.02495 ± 0.130142 |
| Calcium: Week 40 | -0.06416 ± 0.145380 |
| Calcium: Week 52 | -0.03563 ± 0.108627 |
Change from baseline in chemistry parameters: Creatinine, bilirubin, and direct bilirubin was reported.
| micromoles per liter (mcmol/L) | Macitentan |
|---|---|
| Creatinine: Week 4 | -0.2947 ± 4.92719 |
| Creatinine: Week 8 | -4.0411 ± 7.82156 |
| Creatinine: Week 12 | -1.9153 ± 11.69311 |
| Creatinine: Week 16 | -2.5257 ± 8.69784 |
| Creatinine: Week 20 | -2.5257 ± 10.36492 |
| Creatinine: Week 24 | 0.1263 ± 9.20703 |
| Creatinine: Week 28 | -3.5360 ± 8.69741 |
| Creatinine: Week 40 | -1.1366 ± 8.82104 |
| Creatinine: Week 52 | -1.2629 ± 11.22665 |
| Bilirubin: Week 4 | -0.733 ± 1.6688 |
| Bilirubin: Week 8 | 0.733 ± 2.9382 |
| Bilirubin: Week 12 | -0.570 ± 0.8830 |
| Bilirubin: Week 16 | -0.489 ± 0.8344 |
| Bilirubin: Week 20 | 0.489 ± 1.2926 |
| Bilirubin: Week 24 | 0.733 ± 1.6688 |
| Bilirubin: Week 28 | 0.285 ± 0.6981 |
| Bilirubin: Week 40 | 0.244 ± 1.1800 |
| Bilirubin: Week 52 | 0.733 ± 0.9140 |
| Direct Bilirubin: Week 4 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 8 | 0.285 ± 0.6981 |
| Direct Bilirubin: Week 12 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 16 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 20 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 24 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 28 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 40 | 0.000 ± 0.0000 |
| Direct Bilirubin: Week 52 | 0.000 ± 0.0000 |
Change from baseline in chemistry parameter: creatinine clearance was reported.
| milliliters per second (mL/s) | Macitentan |
|---|---|
| Week 4 | 0.08337 ± 0.227335 |
| Week 8 | 0.19291 ± 0.280068 |
| Week 12 | 0.13057 ± 0.353525 |
| Week 16 | 0.16670 ± 0.296181 |
| Week 20 | 0.23817 ± 0.382532 |
| Week 24 | 0.07384 ± 0.285638 |
| Week 28 | 0.23615 ± 0.307994 |
| Week 40 | 0.12623 ± 0.344860 |
| Week 52 | 0.21671 ± 0.540583 |
Change from baseline in chemistry parameter: GFR from Cystatin C Adjusted for BSA was reported.
| mL/second/meter square(mL/s/m^2) | Macitentan |
|---|---|
| Week 4 | 0.05670 ± 0.193047 |
| Wee 8 | 0.11014 ± 0.233865 |
| Week 12 | 0.12838 ± 0.262144 |
| Week 16 | 0.05853 ± 0.181786 |
| Week 20 | 0.07144 ± 0.264242 |
| Week 24 | 0.04350 ± 0.180046 |
| Week 28 | 0.03373 ± 0.182168 |
| Week 40 | 0.06939 ± 0.205418 |
| Week 52 | 0.03863 ± 0.203820 |
Change from baseline in chemistry parameters: AST, ALT, and ALP was reported.
| Enzyme units per liter (Enzyme U/L) | Macitentan |
|---|---|
| AST: Week 4 | 4.2 ± 5.60 |
| AST: Week 8 | 4.5 ± 10.33 |
| AST: Week 12 | -0.8 ± 1.94 |
| AST: Week 16 | -2.0 ± 4.97 |
| AST: Week 20 | 0.1 ± 4.78 |
| AST: Week 24 | 0.8 ± 1.47 |
| AST: Week 28 | -2.2 ± 4.49 |
| AST: Week 40 | 0.1 ± 9.75 |
| AST: Week 52 | -2.9 ± 4.22 |
| ALT: Week 4 | 3.3 ± 4.57 |
| ALT: Week 8 | 1.6 ± 3.69 |
| ALT: Week 12 | 1.2 ± 3.19 |
| ALT: Week 16 | -1.6 ± 3.31 |
| ALT: Week 20 | 0.0 ± 1.41 |
| ALT: Week 24 | 2.6 ± 5.74 |
| ALT: Week 28 | -1.2 ± 2.40 |
| ALT: Week 40 | 1.3 ± 6.21 |
| ALT: Week 52 | 0.4 ± 4.12 |
| ALP: Week 4 | -15.4 ± 47.60 |
| ALP: Week 8 | -12.3 ± 35.45 |
| ALP: Week 12 | -37.2 ± 27.75 |
| ALP: Week 16 | -12.0 ± 48.25 |
| ALP: Week 20 | -21.1 ± 39.81 |
| ALP: Week 24 | 20.7 ± 120.53 |
| ALP: Week 28 | 153.8 ± 436.62 |
| ALP: Week 40 | -37.0 ± 44.79 |
| ALP: Week 52 | -6.4 ± 29.79 |
Change from baseline in vital signs: blood pressure was reported. It included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
| millimeter of mercury (mmHg) | Macitentan |
|---|---|
| SBP: Week 4 | -5.3 ± 12.61 |
| SBP: Week 8 | -5.3 ± 14.86 |
| SBP: Week 12 | 0.4 ± 4.79 |
| SBP: Week 16 | -1.7 ± 10.29 |
| SBP: Week 20 | -1.1 ± 13.35 |
| SBP: Week 24 | -5.3 ± 9.79 |
| SBP: Week 28 | -5.5 ± 6.09 |
| SBP: Week 40 | -3.3 ± 9.05 |
| SBP: Week 52 | -9.3 ± 12.00 |
| DBP: Week 4 | -9.0 ± 9.06 |
| DBP: Week 8 | -4.5 ± 6.41 |
| DBP: Week 12 | -3.7 ± 11.83 |
| DBP: Week 16 | -6.1 ± 11.78 |
| DBP: Week 20 | 0.9 ± 19.04 |
| DBP: Week 24 | -7.1 ± 7.06 |
| DBP: Week 28 | -8.0 ± 8.32 |
| DBP: Week 40 | -0.7 ± 10.13 |
| DBP: Week 52 | -4.0 ± 16.93 |
Change from baseline in vital signs: pulse rate was reported.
| beats per minute | Macitentan |
|---|---|
| Week 4 | -4.4 ± 7.87 |
| Week 8 | -1.7 ± 15.24 |
| Week 12 | -12.1 ± 7.45 |
| Week 16 | -13.4 ± 17.06 |
| Week 20 | -7.4 ± 17.50 |
| Week 24 | -2.4 ± 30.72 |
| Week 28 | -7.2 ± 12.42 |
| Week 40 | -10.3 ± 9.30 |
| Week 52 | -14.7 ± 9.62 |
Change from baseline in ECG: heart rate was reported.
| beats per minute | Macitentan |
|---|---|
| Week 12 | -4.0 ± 19.04 |
| Week 24 | -3.6 ± 25.48 |
| Week 52 | -12.0 ± 8.91 |
Change from baseline in ECG: PR, QRS, QT, QTcB, and QTcF intervals was reported.
| milliseconds (msec) | Macitentan |
|---|---|
| PR Interval: Week 12 | 3.4 ± 10.94 |
| PR Interval: Week 24 | 14.6 ± 15.10 |
| PR Interval: Week 52 | 4.0 ± 7.57 |
| QRS Interval: Week 12 | -0.3 ± 4.96 |
| QRS Interval: Week 24 | 0.3 ± 4.19 |
| QRS Interval: Week 52 | 0.3 ± 3.15 |
| QT Interval: Week 12 | 16.1 ± 29.61 |
| QT Interval: Week 24 | 12.4 ± 34.52 |
| QT Interval: Week 52 | 32.1 ± 16.69 |
| QTcB Interval: Week 12 | 10.6 ± 13.59 |
| QTcB Interval: Week 24 | 4.0 ± 24.53 |
| QTcB Interval: Week 52 | 11.4 ± 13.89 |
| QTcF Interval: Week 12 | 12.6 ± 14.29 |
| QTcF Interval: Week 24 | 6.7 ± 21.16 |
| QTcF Interval: Week 52 | 19.0 ± 11.37 |
Plasma concentration of macitentan was reported.
| nanograms per milliliter (ng/mL) | Macitentan |
|---|---|
| Day 11: 0 hour | 94.4 ± 28.9 |
| Day 11: 1 hour | 93.4 ± 27.7 |
| Day 11: 2 hours | 121 ± 55.1 |
| Day 11: 4 hours | 227 ± 38.5 |
| Day 11: 8 hours | 192 ± 93.2 |
| Day 11: 12 hours | 166 ± 75.5 |
| Day 11: 24 hours | 93.3 ± 26.9 |
| Week 12 | 85.6 ± 37.3 |
Plasma concentration of aprocitentan was reported.
| nanograms per milliliter (ng/mL) | Macitentan |
|---|---|
| Day 11: 0 hour | 993 ± 285 |
| Day 11: 1 hour | 789 ± 228 |
| Day 11: 2 hour | 763 ± 309 |
| Day 11: 4 hour | 944 ± 211 |
| Day 11: 8 hour | 773 ± 308 |
| Day 11: 12 hour | 789 ± 255 |
| Day 11: 24 hour | 929 ± 251 |
| Week 12 | 917 ± 266 |
Plasma concentration of macitentan was reported.
| nanograms per milliliter (ng/mL) | Macitentan |
|---|---|
| Participant 1: Day 1 (2 hours) | 33.6 ± NA |
| Participant 1: Day 1 (5 hours) | 120 ± NA |
| Participant 1: Day 1 (24 hours) | 24.2 ± NA |
| Participant 1: Week 4 | 55.1 ± NA |
| Participant 1: Week 8 | 59.4 ± NA |
| Participant 2: Day 1 (2 hours) | 81.4 ± NA |
| Participant 2: Day 1 (5 hours) | 155 ± NA |
| Participant 2: Day 1 (24 hours) | 61.1 ± NA |
| Participant 2: Week 4 | 143 ± NA |
| Participant 2: Week 8 | 83.5 ± NA |
Plasma concentration of aprocitentan was reported.
| nanograms per milliliter (ng/mL) | Macitentan |
|---|---|
| Participant 1: Day 1 (2 hours) | 7.98 ± NA |
| Participant 1: Day 1 (5 hours) | 65.9 ± NA |
| Participant 1: Day 1 (24 hours) | 162 ± NA |
| Participant 1: Week 4 | 864 ± NA |
| Participant 1: Week 8 | 982 ± NA |
| Participant 2: Day 1 (2 hours) | 7.62 ± NA |
| Participant 2: Day 1 (5 hours) | 29.2 ± NA |
| Participant 2: Day 1 (24 hours) | 119 ± NA |
| Participant 2: Week 4 | 662 ± NA |
| Participant 2: Week 8 | 648 ± NA |
Collected over All-cause mortality: From screening (Day -30) up to Week 56; Serious and Other AEs: From baseline (Day 1) up to Week 56. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Macitentan | 0/7 (0%) | 2/7 (28.6%) | 7/7 (100%) |
| Event | Macitentan |
|---|---|
| BacteraemiaInfections and infestations | 1/7 |
| BronchitisInfections and infestations | 1/7 |
| Metapneumovirus InfectionInfections and infestations | 1/7 |
| Pneumonia BacterialInfections and infestations | 1/7 |
| Event | Macitentan |
|---|---|
| NasopharyngitisInfections and infestations | 6/7 |
| PyrexiaGeneral disorders | 4/7 |
| Adenovirus InfectionInfections and infestations | 3/7 |
| Streptococcal InfectionInfections and infestations | 3/7 |
| Abdominal PainGastrointestinal disorders | 2/7 |
| ConjunctivitisInfections and infestations | 2/7 |
| Arthropod BiteInjury, poisoning and procedural complications | 2/7 |
| Iron Deficiency AnaemiaBlood and lymphatic system disorders | 1/7 |
| NeutropeniaBlood and lymphatic system disorders | 1/7 |
| Conjunctivitis AllergicEye disorders | 1/7 |
| Age, Customized(Participants) | Macitentan |
|---|---|
| < 2 years | 2 |
| >= 2 years | 5 |
| Sex: Female, Male(Participants) | Macitentan |
|---|---|
| Female | 3 |
| Male | 4 |
| Ethnicity (NIH/OMB)(Participants) | Macitentan |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 7 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Macitentan |
|---|---|
| Japan | 7 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Data sharing details ↗ · www.janssen.com
Ran from Nov 2022 to primary completion in Aug 2024, 21 months.
Results were first posted in Oct 2025, 1 year 1 month after primary completion.
Of 43 industry-sponsored phase 3 interventional studies under Pulmonary Arterial Hypertension, half reached primary completion within 50 months of starting (the median), counting those still running; a quarter within 31 and three quarters within 83. This study's 21 months is below that.
Counting every sponsor, half of 49 studies reached it within 50 months; a quarter within 31 and three quarters within 83.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Macitentan
Pulmonary Arterial Hypertension →