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    Clinical Trial Results:
    A Multicenter, Open-label, Phase III Study to Assess the Efficacy, Safety, and Pharmacokinetics of Macitentan in Japanese Pediatric Patients (>=3 months to <15 years) with Pulmonary Arterial Hypertension

    Summary
    EudraCT number
    		 2023-000984-30
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    04 Mar 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    67896062PAH3001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05167825
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Janssen Pharmaceutical K.K.
    Sponsor organisation address
    Nishi-kanda, Chiyoda-ku, Tokyo, Japan, 3-5-2
    Public contact
    Clinical Registry Group, Janssen Pharmaceutical K.K., ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Pharmaceutical K.K., ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Mar 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Mar 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to evaluate the effect of macitentan on hemodynamic measures at Week 24.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Nov 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 7
    Worldwide total number of subjects
    7
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    2
    Children (2-11 years)
    4
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 7 participants were enrolled and treated in the study.

    Pre-assignment
    Screening details
    		 A total of 7 participants were enrolled and treated in the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not blinded

    Arms
    Arm title
    		 Macitentan
    Arm description
    		 Participants 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Macitentan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants aged between 3 months and 14 years, inclusive with PAH received macitentan 1 mg or 2.5 mg tablets orally once daily based on age and body weight. Participants  aged >=3 months to <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 kg 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.

    Number of subjects in period 1
    		Macitentan
    Started
    7
    Completed
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Macitentan
    Reporting group description
    		 Participants 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.

    Reporting group values
    		 Macitentan Total
    Number of subjects
    		 7 7
    Age categorical
    Units: Subjects
        In Utero
    		 0 0
        Preterm newborn infants (gestional age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days - 23 months)
    		 2 2
        Children (2 - 11 years)
    		 4 4
        12 - 17 years
    		 1 1
        Adults (18 - 64 years)
    		 0 0
        From 65 - 84 years
    		 0 0
        85 years and over
    		 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 5.7 ( 5.12 ) -
    Title for Gender
    Units: subjects
        Female
    		 3 3
        Male
    		 4 4

    End points

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    End points reporting groups
    Reporting group title
    Macitentan
    Reporting group description
    		 Participants 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.

    Primary: Fold Change from Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI)

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    End point title
    		 Fold Change from Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI) [1]
    End point description
    PVRI fold change at Week 24 was calculated as: 100* (PVRI at Week 24/PVRI at baseline). PVR was determined by right heart catheterization. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned for this endpoint. No inferential statistics was planned.
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: percent change
        geometric mean (geometric coefficient of variation)
    59.43 ( 75.1 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: PVR was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: wood units (WU)
        arithmetic mean (standard deviation)
    -3.734 ( 4.4971 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: mRAP was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: millimeters of mercury (mmHg)
        arithmetic mean (standard deviation)
    -2.9 ( 8.57 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Atrial Pressure (mPAP)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Atrial Pressure (mPAP)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: mPAP was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: millimeters of mercury (mmHg)
        arithmetic mean (standard deviation)
    -8.0 ( 12.62 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: CI was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: liters/minute/meter square (L/min/m^2)
        arithmetic mean (standard deviation)
    -0.03 ( 1.019 )
    No statistical analyses for this end point

    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)

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    End point title
    		 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)
    End point description
    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. Analysis population included all participants greater than (>) 4 years of age.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    3
    Units: Participants
        Baseline
    0
        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
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2])

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    End point title
    		 Percent Change from Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2])
    End point description
    Change from baseline to Week 24 in hemodynamic variable: SvO(2) was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: percent change
        arithmetic mean (standard deviation)
    -2.9 ( 9.37 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: CO was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: liters per minute (L/min)
        arithmetic mean (standard deviation)
    0.07 ( 0.743 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR)

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    End point title
    		 Change from Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR)
    End point description
    Change from baseline to Week 24 in hemodynamic variable: TPR was reported. TPR was calculated as: (mPAP/CO)*80. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Week 24
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: dynes second/centimeter^5
        arithmetic mean (standard deviation)
    -243.0 ( 410.13 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Change from Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama Functional Class (FC)

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    End point title
    		 Number of Participants With Change from Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama Functional Class (FC)
    End point description
    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 (eg: 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 improved in were classified into Improved(reduction in FC), No change(no change in FC) and Worsened(increase in FC).Efficacy analysis set was used.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
        Baseline
    0
        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
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)

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    End point title
    		 Change from Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)
    End point description
    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. Analysis population included all participants greater than equal to (>=) 6 years of age. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 24 and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    3
    Units: meters
    arithmetic mean (standard deviation)
        Week 24 (n=3)
    4.897 ( 43.6657 )
        Week 52 (n=2)
    24.710 ( 105.6559 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 12, 24, 28, 40, and 52 in N-terminal Pro–brain Natriuretic Peptide (NT-proBNP)

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    End point title
    		 Change from Baseline to Weeks 12, 24, 28, 40, and 52 in N-terminal Pro–brain Natriuretic Peptide (NT-proBNP)
    End point description
    Change from baseline to Weeks 12, 24, 28, 40, and 52 in NT-proBNP was reported. Efficacy analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, 28, 40, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: picograms per milliliter (pg/mL)
    arithmetic mean (standard deviation)
        Week 12 (n=7)
    6.5911 ( 18.85065 )
        Week 24 (n=7)
    -3.7423 ( 7.79983 )
        Week 28 (n=6)
    -3.1663 ( 20.38136 )
        Week 40 (n=7)
    -5.7146 ( 14.23745 )
        Week 52 (n=6)
    -0.2360 ( 10.15074 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE)

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    End point title
    		 Change from Baseline to Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE)
    End point description
    Change from baseline to Weeks 12, 24, and 52 in TAPSE was reported. It is 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. Efficacy analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: millimeters per meter square (mm/m^2)
    arithmetic mean (standard deviation)
        Week 12 (n=7)
    2.766 ( 1.6763 )
        Week 24 (n=7)
    1.873 ( 1.0379 )
        Week 52 (n=6)
    2.412 ( 1.3666 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI)

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    End point title
    		 Change from Baseline to Weeks 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI)
    End point description
    Change from baseline to Weeks 12, 24, and 52 in LVEI was reported. It included diastolic (D) LVEI and systolic (S) LVEI. 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. Efficacy analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Ratio
    arithmetic mean (standard deviation)
        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 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 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)

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    End point title
    		 Change from Baseline to Weeks 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)
    End point description
    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. Analysis population included all participants >=2 years of age. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Total score parents/caregiver report:Week 12(n=5)
    8.905 ( 6.1274 )
        Total score parents/caregiver report:Week 24(n=5)
    8.190 ( 11.3259 )
        Total score parents/caregiver report:Week 52(n=5)
    15.810 ( 7.8366 )
        Total score - participant report: Week 12 (n=3)
    8.889 ( 3.4694 )
        Total score - participant report: Week 24 (n=3)
    -2.222 ( 17.8211 )
        Total score - participant report: Week 52 (n=3)
    16.667 ( 20.2759 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Number of Hours of Daytime Activity

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    End point title
    		 Change from Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Number of Hours of Daytime Activity
    End point description
    Change from baseline to Weeks 12, 24, and 52 in physical activity as measured by accelerometry: number of hours of daytime activity was reported. Analysis population included all participants >=2 years of age.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: hours
    arithmetic mean (standard deviation)
        Week 12
    -0.929 ( 0.9741 )
        Week 24
    -0.280 ( 1.3553 )
        Week 52
    0.144 ( 0.4985 )
    No statistical analyses for this end point

    Secondary: Change from Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Count Per Minute of Daily Activity

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    End point title
    		 Change from Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Count Per Minute of Daily Activity
    End point description
    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. Analysis population included all participants >=2 years of age.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: counts per minute
    arithmetic mean (standard deviation)
        Week 12
    73.946 ( 205.4249 )
        Week 24
    112.733 ( 219.3168 )
        Week 52
    125.427 ( 157.5824 )
    No statistical analyses for this end point

    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

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    End point title
    		 Change from Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Light Physical Activity
    End point description
    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. Analysis population included all participants >=2 years of age.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: minutes
    arithmetic mean (standard deviation)
        Week 12
    1.600 ( 46.5857 )
        Week 24
    35.159 ( 92.2011 )
        Week 52
    38.852 ( 57.1818 )
    No statistical analyses for this end point

    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

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    End point title
    		 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
    End point description
    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. Analysis population included all participants >=2 years of age.
    End point type
    Secondary
    End point timeframe
    From baseline (Day 1) up to Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: minutes
    arithmetic mean (standard deviation)
        Week 12
    0.032 ( 0.4424 )
        Week 24
    0.169 ( 0.6058 )
        Week 52
    0.493 ( 1.5023 )
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Macitentan: Participants >=2 Years Old

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    End point title
    		 Plasma Concentration of Macitentan: Participants >=2 Years Old
    End point description
    Plasma concentration of macitentan was reported. Analysis population included all participants >=2 years of age. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Day 11: 0 hour (n=5)
    94.4 ( 28.9 )
        Day 11: 1 hour (n=5)
    93.4 ( 27.7 )
        Day 11: 2 hours (n=5)
    121 ( 55.1 )
        Day 11: 4 hours (n=5)
    227 ( 38.5 )
        Day 11: 8 hours (n=5)
    192 ( 93.2 )
        Day 11: 12 hours (n=5)
    166 ( 75.5 )
        Day 11: 24 hours (n=5)
    93.3 ( 26.9 )
        Week 12 (n=4)
    85.6 ( 37.3 )
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Aprocitentan: Participants >=2 Years Old

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    End point title
    		 Plasma Concentration of Aprocitentan: Participants >=2 Years Old
    End point description
    Plasma concentration of aprocitentan was reported. Analysis population included all participants >=2 years of age. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Day 11 (0, 1, 2, 4, 8, 12, 24 hours post-dose), Week 12
    End point values
    		 Macitentan
    Number of subjects analysed
    5
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Day 11: 0 hour (n=5)
    993 ( 285 )
        Day 11: 1 hour (n=5)
    789 ( 228 )
        Day 11: 2 hours (n=5)
    763 ( 309 )
        Day 11: 4 hours (n=5)
    944 ( 211 )
        Day 11: 8 hours (n=5)
    773 ( 308 )
        Day 11: 12 hours (n=5)
    789 ( 255 )
        Day 11: 24 hours (n=5)
    929 ( 251 )
        Week 12 (n=4)
    917 ( 266 )
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Macitentan: Participants <2 Years Old

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    End point title
    		 Plasma Concentration of Macitentan: Participants <2 Years Old
    End point description
    Plasma concentration of macitentan was reported. The data was not summarized since N=2, hence participants wise data was reported. Analysis population included all participants <2 years of age. Here, "99999" refers to standard deviation not evaluable for single participant.
    End point type
    Secondary
    End point timeframe
    Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8
    End point values
    		 Macitentan
    Number of subjects analysed
    2
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Participant 1: Day 1 (2 hours)
    33.6 ( 99999 )
        Participant 1: Day 1 (5 hours)
    120 ( 99999 )
        Participant 1: Day 1 (24 hours)
    24.2 ( 99999 )
        Participant 1: Week 4
    55.1 ( 99999 )
        Participant 1: Week 8
    59.4 ( 99999 )
        Participant 2: Day 1 (2 hours)
    81.4 ( 99999 )
        Participant 2: Day 1 (5 hours)
    155 ( 99999 )
        Participant 2: Day 1 (24 hours)
    61.1 ( 99999 )
        Participant 2: Week 4
    143 ( 99999 )
        Participant 2: Week 8
    83.5 ( 99999 )
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Aprocitentan: Participants <2 Years Old

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    End point title
    		 Plasma Concentration of Aprocitentan: Participants <2 Years Old
    End point description
    Plasma concentration of aprocitentan was reported. The data was not summarized since N=2, hence participants wise data was reported. Analysis population included all participants <2 years of age. Here, "99999" refers to standard deviation not evaluable for single participant.
    End point type
    Secondary
    End point timeframe
    Day 1 (2, 5, 24 hours post-dose), Weeks 4 and 8
    End point values
    		 Macitentan
    Number of subjects analysed
    2
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        Participant 1: Day 1 (2 hours)
    7.98 ( 99999 )
        Participant 1: Day 1 (5 hours)
    65.9 ( 99999 )
        Participant 1: Day 1 (24 hours)
    162 ( 99999 )
        Participant 1: Week 4
    864 ( 99999 )
        Participant 1: Week 8
    982 ( 99999 )
        Participant 2: Day 1 (2 hours)
    7.62 ( 99999 )
        Participant 2: Day 1 (5 hours)
    29.2 ( 99999 )
        Participant 2: Day 1 (24 hours)
    119 ( 99999 )
        Participant 2: Week 4
    662 ( 99999 )
        Participant 2: Week 8
    648 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index

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    End point title
    		 Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index
    End point description
    Change from baseline to Weeks 24 and 52 in Borg dyspnea index 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. Analysis population included all participants greater than equal to (>=) 6 years of age. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 24 and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    3
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Before 6MWT: Week 24 (n=3)
    0.00 ( 0.000 )
        Before 6MWT: Week 52 (n=2)
    0.00 ( 0.000 )
        After 6MWT: Week 24 (n=3)
    -1.17 ( 0.764 )
        After 6MWT: Week 52 (n=2)
    -1.00 ( 0.707 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants With Treatment-emergent Adverse Events (TEAEs)
    End point description
    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. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) up to Week 56
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
    7
    No statistical analyses for this end point

    Secondary: Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values

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    End point title
    		 Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values
    End point description
    Number of participants with postbaseline markedly abnormal hematology laboratory values was reported. Abnormality was judged at the discretion of investigator. Data is reported for categories where atleast one participant had abnormality. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Weeks 20, 40, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
        Hematocrit:<0.28% of blood cells(<0.32M): Week 20
    1
        Hemoglobin: < 100 grams per liter (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
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs of Special Interest

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    End point title
    		 Number of Participants With TEAEs of Special Interest
    End point description
    Number of participants with TEAEs of special interest was reported. It included anemia/decreased hemoglobin level, oedema/fluid retention, hepatic impairment and hypotension. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) up to Week 56
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
    End point description
    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. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) up to Week 56
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With AEs Leading to Premature Discontinuation of Study Drug

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    End point title
    		 Number of Participants With AEs Leading to Premature Discontinuation of Study Drug
    End point description
    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. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) up to Week 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values

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    End point title
    		 Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values
    End point description
    Number of participants with postbaseline markedly abnormal clinical chemistry laboratory values was reported. Abnormality was judged at the discretion of investigator. Data is reported for categories where atleast one participant had abnormality. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Weeks 4 and 28
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Participants
        Potassium: >6.0 mmol/L: Week 4 (n=7)
    1
        Calcium: <1.75 mmol/L: Week 4 (n=7)
    1
        ALP: > 2.5 * ULN: Week 28 (n=6)
    1
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Pulse Rate

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    End point title
    		 Change from Baseline in Vital Signs: Pulse Rate
    End point description
    Change from baseline in vital signs: pulse rate was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: beats per minute
    arithmetic mean (standard deviation)
        Week 4 (n=7)
    -4.4 ( 7.87 )
        Week 8 (n=7)
    -1.7 ( 15.24 )
        Week 12 (n=7)
    -12.1 ( 7.45 )
        Week 16 (n=7)
    -13.4 ( 17.06 )
        Week 20 (n=7)
    -7.4 ( 17.50 )
        Week 24 (n=7)
    -2.4 ( 30.72 )
        Week 28 (n=6)
    -7.2 ( 12.42 )
        Week 40 (n=7)
    -10.3 ( 9.30 )
        Week 52 (n=7)
    -14.7 ( 9.62 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Blood Pressure

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    End point title
    		 Change from Baseline in Vital Signs: Blood Pressure
    End point description
    Change from baseline in vital signs: blood pressure was reported. It included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP: Week 4 (n=7)
    -5.3 ( 12.61 )
        SBP: Week 8 (n=7)
    -5.3 ( 14.86 )
        SBP: Week 12 (n=7)
    0.4 ( 4.79 )
        SBP: Week 16 (n=7)
    -1.7 ( 10.29 )
        SBP: Week 20 (n=7)
    -1.1 ( 13.35 )
        SBP: Week 24 (n=7)
    -5.3 ( 9.79 )
        SBP: Week 28 (n=6)
    -5.5 ( 6.09 )
        SBP: Week 40 (n=7)
    -3.3 ( 9.05 )
        SBP: Week 52 (n=7)
    -9.3 ( 12.00 )
        DBP: Week 4 (n=6)
    -9.0 ( 9.06 )
        DBP: Week 8 (n=6)
    -4.5 ( 6.41 )
        DBP: Week 12 (n=7)
    -3.7 ( 11.83 )
        DBP: Week 16 (n=7)
    -6.1 ( 11.78 )
        DBP: Week 20 (n=7)
    0.9 ( 19.04 )
        DBP: Week 24 (n=7)
    -7.1 ( 7.06 )
        DBP: Week 28 (n=6)
    -8.0 ( 8.32 )
        DBP: Week 40 (n=7)
    -0.7 ( 10.13 )
        DBP: Week 52 (n=7)
    -4.0 ( 16.93 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Electrocardiogram (ECG) Parameter: Heart Rate

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    End point title
    		 Change from Baseline in Electrocardiogram (ECG) Parameter: Heart Rate
    End point description
    Change from baseline in ECG: heart rate was reported. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: beats per minute
    arithmetic mean (standard deviation)
        Week 12
    -4.0 ( 19.04 )
        Week 24
    -3.6 ( 25.48 )
        Week 52
    -12.0 ( 8.91 )
    No statistical analyses for this end point

    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) Intervals

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    End point title
    		 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) Intervals
    End point description
    Change from baseline in ECG: PR, QRS, QT, QTcB, and QTcF intervals was reported. Safety analysis set included all participants who took at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 12, 24, and 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: milliseconds (msec)
    arithmetic mean (standard deviation)
        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 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils Band Form (NBF), Lymphocytes, Monocytes, Eosinophils, and Basophils

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    End point title
    		 Change from Baseline in Hematology Parameters: Platelets, Leukocytes, Neutrophils Band Form (NBF), Lymphocytes, Monocytes, Eosinophils, and Basophils
    End point description
    Change from baseline in hematology parameters: platelets, leukocytes, NBF, lymphocytes, monocytes, eosinophils, and basophils was reported. Data for each parameters was planned to be reported at specified timepoints only. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints. Here, "99999" refers to standard deviation data was not calculated for single participant
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: 10^9 cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Platelets: Week 4 (n=7)
    -20.4 ( 31.90 )
        Platelets: Week 8 (n=7)
    -47.9 ( 42.32 )
        Platelets: Week 12 (n=7)
    -23.3 ( 70.86 )
        Platelets: Week 16 (n=7)
    -41.3 ( 53.21 )
        Platelets: Week 20 (n=7)
    -42.4 ( 86.32 )
        Platelets: Week 24 (n=7)
    -42.6 ( 77.72 )
        Platelets: Week 28 (n=6)
    -22.0 ( 59.29 )
        Platelets: Week 40 (n=7)
    -40.3 ( 106.10 )
        Platelets: Week 52 (n=7)
    -56.7 ( 92.37 )
        Leukocytes: Week 4 (n=7)
    0.031 ( 3.7398 )
        Leukocytes: Week 8 (n=7)
    0.549 ( 3.4816 )
        Leukocytes: Week 12 (n=7)
    -0.131 ( 2.3574 )
        Leukocytes: Week 16 (n=7)
    -0.321 ( 1.5230 )
        Leukocytes: Week 20 (n=7)
    -1.256 ( 3.7745 )
        Leukocytes: Week 24 (n=7)
    0.214 ( 3.6431 )
        Leukocytes: Week 28 (n=6)
    -0.347 ( 2.8012 )
        Leukocytes: Week 40 (n=7)
    -1.660 ( 3.0486 )
        Leukocytes: Week 52 (n=7)
    -0.541 ( 2.7583 )
        NBF: Week 8 (n=1)
    0.120 ( 99999 )
        NBF: Week 16 (n=1)
    0.480 ( 99999 )
        NBF: Week 20 (n=2)
    0.055 ( 0.1485 )
        NBF: Week 40 (n=1)
    -0.050 ( 99999 )
        NBF: Week 52 (n=1)
    -0.030 ( 99999 )
        Lymphocytes: Week 4 (n=7)
    -0.144 ( 0.4446 )
        Lymphocytes: Week 8 (n=7)
    -0.240 ( 0.5289 )
        Lymphocytes: Week 12 (n=7)
    -0.451 ( 0.3151 )
        Lymphocytes: Week 16 (n=7)
    -0.294 ( 0.1784 )
        Lymphocytes: Week 20 (n=7)
    -0.286 ( 0.8204 )
        Lymphocytes: Week 24 (n=7)
    -0.224 ( 0.5638 )
        Lymphocytes: Week 28 (n=6)
    -0.255 ( 0.5392 )
        Lymphocytes: Week 40 (n=7)
    -0.649 ( 0.5258 )
        Lymphocytes: Week 52 (n=7)
    -0.411 ( 0.5227 )
        Monocytes: Week 4 (n=7)
    -0.029 ( 0.0807 )
        Monocytes: Week 8 (n=7)
    0.070 ( 0.2063 )
        Monocytes: Week 12 (n=7)
    0.033 ( 0.0925 )
        Monocytes: Week 16 (n=7)
    -0.046 ( 0.0382 )
        Monocytes: Week 20 (n=7)
    -0.081 ( 0.0928 )
        Monocytes: Week 24 (n=7)
    0.017 ( 0.1042 )
        Monocytes: Week 28 (n=6)
    -0.052 ( 0.0884 )
        Monocytes: Week 40 (n=7)
    -0.103 ( 0.0911 )
        Monocytes: Week 52 (n=7)
    -0.086 ( 0.0988 )
        Eosinophils: Week 4 (n=7)
    -0.011 ( 0.0811 )
        Eosinophils: Week 8 (n=7)
    -0.009 ( 0.0795 )
        Eosinophils: Week 12 (n=7)
    0.066 ( 0.1153 )
        Eosinophils: Week 16 (n=7)
    0.030 ( 0.1606 )
        Eosinophils: Week 20 (n=7)
    0.086 ( 0.1752 )
        Eosinophils: Week 24 (n=7)
    -0.016 ( 0.1066 )
        Eosinophils: Week 28 (n=6)
    -0.040 ( 0.1119 )
        Eosinophils: Week 40 (n=7)
    0.000 ( 0.0693 )
        Eosinophils: Week 52 (n=7)
    0.220 ( 0.6577 )
        Basophils: Week 4 (n=7)
    0.016 ( 0.0162 )
        Basophils: Week 8 (n=7)
    0.009 ( 0.0273 )
        Basophils: Week 12 (n=7)
    0.016 ( 0.0270 )
        Basophils: Week 16 (n=7)
    0.016 ( 0.0465 )
        Basophils: Week 20 (n=7)
    0.000 ( 0.0183 )
        Basophils: Week 24 (n=7)
    0.016 ( 0.0257 )
        Basophils: Week 28 (n=6)
    0.008 ( 0.0256 )
        Basophils: Week 40 (n=7)
    -0.004 ( 0.0276 )
        Basophils: Week 52 (n=7)
    0.053 ( 0.1073 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hematology Parameter: Hematocrit

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    End point title
    		 Change from Baseline in Hematology Parameter: Hematocrit
    End point description
    Change from baseline in hematology parameter: hematocrit was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Percentage of blood cells
    arithmetic mean (standard deviation)
        Week 4 (n=7)
    0.009 ( 0.0204 )
        Week 8 (n=7)
    0.016 ( 0.0223 )
        Week 12 (n=7)
    0.004 ( 0.0230 )
        Week 16 (n=7)
    -0.006 ( 0.0299 )
        Week 20 (n=7)
    -0.004 ( 0.0282 )
        Week 24 (n=7)
    0.006 ( 0.0355 )
        Week 28 (n=6)
    0.010 ( 0.0237 )
        Week 40 (n=7)
    0.010 ( 0.0216 )
        Week 52 (n=7)
    0.010 ( 0.0404 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hematology Parameter: Hemoglobin

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    End point title
    		 Change from Baseline in Hematology Parameter: Hemoglobin
    End point description
    Change from baseline in hematology parameter: hemoglobin was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 4 (n=7)
    1.9 ( 9.12 )
        Week 8 (n=7)
    2.3 ( 8.28 )
        Week 12 (n=7)
    -0.1 ( 9.60 )
        Week 16 (n=7)
    -3.0 ( 9.35 )
        Week 20 (n=7)
    -4.1 ( 5.84 )
        Week 24 (n=7)
    -0.3 ( 9.81 )
        Week 28 (n=6)
    -2.7 ( 8.71 )
        Week 40 (n=7)
    0.1 ( 8.91 )
        Week 52 (n=7)
    0.7 ( 11.84 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hematology Parameter: Erythrocytes

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    End point title
    		 Change from Baseline in Hematology Parameter: Erythrocytes
    End point description
    Change from baseline in hematology parameter: erythrocytes was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: 10^12 cells per liter (10^12/L)
    arithmetic mean (standard deviation)
        Week 4 (n=7)
    0.03 ( 0.236 )
        Week 8 (n=7)
    0.13 ( 0.309 )
        Week 12 (n=7)
    0.04 ( 0.336 )
        Week 16 (n=7)
    -0.07 ( 0.269 )
        Week 20 (n=7)
    -0.06 ( 0.230 )
        Week 24 (n=7)
    0.04 ( 0.299 )
        Week 28 (n=6)
    0.07 ( 0.266 )
        Week 40 (n=7)
    0.07 ( 0.335 )
        Week 52 (n=7)
    0.04 ( 0.412 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Chemistry Parameters: Sodium, Potassium, Urea Nitrogen, Glucose, and Calcium

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    End point title
    		 Change from Baseline in Chemistry Parameters: Sodium, Potassium, Urea Nitrogen, Glucose, and Calcium
    End point description
    Change from baseline in chemistry parameters: sodium, potassium, urea nitrogen, glucose, and calcium was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: 10^12 cells per liter (10^12/L)
    arithmetic mean (standard deviation)
        Sodium: Week 4 (n=7)
    -0.1 ( 3.85 )
        Sodium: Week 8 (n=7)
    0.1 ( 1.57 )
        Sodium: Week 12 (n=6)
    0.2 ( 1.17 )
        Sodium: Week 16 (n=7)
    -0.7 ( 1.98 )
        Sodium: Week 20 (n=7)
    -0.1 ( 2.34 )
        Sodium: Week 24 (n=7)
    0.3 ( 2.98 )
        Sodium: Week 28 (n=6)
    1.5 ( 1.87 )
        Sodium: Week 40 (n=7)
    -0.1 ( 2.04 )
        Sodium: Week 52 (n=7)
    -0.7 ( 2.43 )
        Potassium: Week 4 (n=7)
    0.46 ( 1.137 )
        Potassium: Week 8 (n=7)
    0.03 ( 0.330 )
        Potassium: Week 12 (n=6)
    0.10 ( 0.494 )
        Potassium: Week 16 (n=7)
    -0.09 ( 0.234 )
        Potassium: Week 20 (n=7)
    0.03 ( 0.315 )
        Potassium: Week 24 (n=7)
    -0.09 ( 0.261 )
        Potassium: Week 28 (n=6)
    -0.07 ( 0.186 )
        Potassium: Week 40 (n=7)
    0.07 ( 0.298 )
        Potassium: Week 52 (n=7)
    0.04 ( 0.336 )
        Urea Nitrogen: Week 4 (n=7)
    -0.0510 ( 1.32665 )
        Urea Nitrogen: Week 8 (n=7)
    -0.3060 ( 1.32665 )
        Urea Nitrogen: Week 12 (n=6)
    0.0000 ( 1.39184 )
        Urea Nitrogen: Week 16 (n=7)
    0.3060 ( 1.19170 )
        Urea Nitrogen: Week 20 (n=7)
    -0.8160 ( 1.10448 )
        Urea Nitrogen: Week 24 (n=7)
    -0.1020 ( 1.14229 )
        Urea Nitrogen: Week 28 (n=6)
    -0.3570 ( 0.98418 )
        Urea Nitrogen: Week 40 (n=7)
    -0.8160 ( 1.40875 )
        Urea Nitrogen: Week 52 (n=7)
    -0.3060 ( 1.84847 )
        Glucose: Week 4 (n=7)
    0.34099 ( 0.601656 )
        Glucose: Week 8 (n=7)
    0.22204 ( 0.652101 )
        Glucose: Week 12 (n=6)
    0.05548 ( 0.641615 )
        Glucose: Week 16 (n=7)
    0.35684 ( 0.503536 )
        Glucose: Week 20 (n=7)
    0.47580 ( 0.527417 )
        Glucose: Week 24 (n=7)
    0.60266 ( 0.730401 )
        Glucose: Week 28 (n=6)
    0.60133 ( 0.933768 )
        Glucose: Week 40 (n=7)
    0.39649 ( 0.628362 )
        Glucose: Week 52 (n=7)
    0.00791 ( 0.554573 )
        Calcium: Week 4 (n=7)
    -0.09980 ( 0.293456 )
        Calcium: Week 8 (n=7)
    -0.00357 ( 0.098172 )
        Calcium: Week 12 (n=6)
    -0.04158 ( 0.068184 )
        Calcium: Week 16 (n=7)
    -0.04634 ( 0.124293 )
        Calcium: Week 20 (n=7)
    -0.07486 ( 0.097716 )
        Calcium: Week 24 (n=7)
    -0.03564 ( 0.097564 )
        Calcium: Week 28 (n=6)
    -0.02495 ( 0.130142 )
        Calcium: Week 40 (n=7)
    -0.06416 ( 0.145380 )
        Calcium: Week 52 (n=7)
    -0.03563 ( 0.108627 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Chemistry Parameters: Creatinine (Jaffe Reaction), Bilirubin, and Direct Bilirubin,

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    End point title
    		 Change from Baseline in Chemistry Parameters: Creatinine (Jaffe Reaction), Bilirubin, and Direct Bilirubin,
    End point description
    Change from baseline in chemistry parameters: creatinine, bilirubin, and direct bilirubin was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: micromoles per liter (mcmol/L)
    arithmetic mean (standard deviation)
        Creatinine: Week 4 (n=6)
    -0.2947 ( 4.92719 )
        Creatinine: Week 8 (n=7)
    -4.0411 ( 7.82156 )
        Creatinine: Week 12 (n=6)
    -1.9153 ( 11.69311 )
        Creatinine: Week 16 (n=7)
    -2.5257 ( 8.69784 )
        Creatinine: Week 20 (n=7)
    -2.5257 ( 10.36492 )
        Creatinine: Week 24 (n=7)
    0.1263 ( 9.20703 )
        Creatinine: Week 28 (n=6)
    -3.5360 ( 8.69741 )
        Creatinine: Week 40 (n=7)
    -1.1366 ( 8.82104 )
        Creatinine: Week 52 (n=7)
    -1.2629 ( 11.22665 )
        Bilirubin: Week 4 (n=7)
    -0.733 ( 1.6688 )
        Bilirubin: Week 8 (n=7)
    0.733 ( 2.9382 )
        Bilirubin: Week 12 (n=6)
    -0.570 ( 0.8830 )
        Bilirubin: Week 16 (n=7)
    -0.489 ( 0.8344 )
        Bilirubin: Week 20 (n=7)
    0.489 ( 1.2926 )
        Bilirubin: Week 24 (n=7)
    0.733 ( 1.6688 )
        Bilirubin: Week 28 (n=6)
    0.285 ( 0.6981 )
        Bilirubin: Week 40 (n=7)
    0.244 ( 1.1800 )
        Bilirubin: Week 52 (n=7)
    0.733 ( 0.9140 )
        Direct Bilirubin: Week 4 (n=5)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 8 (n=6)
    0.285 ( 0.6981 )
        Direct Bilirubin: Week 12 (n=6)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 16 (n=6)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 20 (n=7)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 24 (n=6)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 28 (n=6)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 40 (n=7)
    0.000 ( 0.0000 )
        Direct Bilirubin: Week 52 (n=5)
    0.000 ( 0.0000 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Chemistry Parameters: Creatinine Clearance

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    End point title
    		 Change from Baseline in Chemistry Parameters: Creatinine Clearance
    End point description
    Change from baseline in chemistry parameter: creatinine clearance was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: milliliters per second (mL/s)
    arithmetic mean (standard deviation)
        Week 4 (n=6)
    0.08337 ( 0.227335 )
        Week 8 (n=7)
    0.19291 ( 0.280068 )
        Week 12 (n=6)
    0.13057 ( 0.353525 )
        Week 16 (n=7)
    0.16670 ( 0.296181 )
        Week 20 (n=7)
    0.23817 ( 0.382532 )
        Week 24 (n=7)
    0.07384 ( 0.285638 )
        Week 28 (n=6)
    0.23615 ( 0.307994 )
        Week 40 (n=7)
    0.12623 ( 0.344860 )
        Week 52 (n=7)
    0.21671 ( 0.540583 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Chemistry Parameters: Glomerular Filtration Rate (GFR) from Cystatin C Adjusted for Body Surface Area (BSA)

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    End point title
    		 Change from Baseline in Chemistry Parameters: Glomerular Filtration Rate (GFR) from Cystatin C Adjusted for Body Surface Area (BSA)
    End point description
    Change from baseline in chemistry parameter: GFR from Cystatin C Adjusted for BSA was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: mL/second/meter square(mL/s/m^2)
    arithmetic mean (standard deviation)
        Week 4 (n=7)
    0.05670 ( 0.193047 )
        Week 8 (n=7)
    0.11014 ( 0.233865 )
        Week 12 (n=6)
    0.12838 ( 0.262144 )
        Week 16 (n=7)
    0.05853 ( 0.181786 )
        Week 20 (n=7)
    0.07144 ( 0.264242 )
        Week 24 (n=7)
    0.04350 ( 0.180046 )
        Week 28 (n=6)
    0.03373 ( 0.182168 )
        Week 40 (n=7)
    0.06939 ( 0.205418 )
        Week 52 (n=7)
    0.03863 ( 0.203820 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP)

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    End point title
    		 Change from Baseline in Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP)
    End point description
    Change from baseline in chemistry parameters: AST, ALT, and ALP was reported. Safety analysis set included all participants who took at least 1 dose of study intervention. Here, "n" (number analyzed) refer to the number of participants evaluable at specified timepoints.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 8, 12, 16, 20, 24, 28, 40, 52
    End point values
    		 Macitentan
    Number of subjects analysed
    7
    Units: Enzyme units per liter (Enzyme U/L)
    arithmetic mean (standard deviation)
        AST: Week 4 (n=6)
    4.2 ( 5.60 )
        AST: Week 8 (n=6)
    4.5 ( 10.33 )
        AST: Week 12 (n=6)
    -0.8 ( 1.94 )
        AST: Week 16 (n=7)
    -2.0 ( 4.97 )
        AST: Week 20 (n=7)
    0.1 ( 4.78 )
        AST: Week 24 (n=6)
    0.8 ( 1.47 )
        AST: Week 28 (n=6)
    -2.2 ( 4.49 )
        AST: Week 40 (n=7)
    0.1 ( 9.75 )
        AST: Week 52 (n=7)
    -2.9 ( 4.22 )
        ALT: Week 4 (n=7)
    3.3 ( 4.57 )
        ALT: Week 8 (n=7)
    1.6 ( 3.69 )
        ALT: Week 12 (n=6)
    1.2 ( 3.19 )
        ALT: Week 16 (n=7)
    -1.6 ( 3.31 )
        ALT: Week 20 (n=7)
    0.0 ( 1.41 )
        ALT: Week 24 (n=7)
    2.6 ( 5.74 )
        ALT: Week 28 (n=6)
    -1.2 ( 2.40 )
        ALT: Week 40 (n=7)
    1.3 ( 6.21 )
        ALT: Week 52 (n=7)
    0.4 ( 4.12 )
        ALP: Week 4 (n=7)
    -15.4 ( 47.60 )
        ALP: Week 8 (n=7)
    -12.3 ( 35.45 )
        ALP: Week 12 (n=6)
    -37.2 ( 27.75 )
        ALP: Week 16 (n=7)
    -12.0 ( 48.25 )
        ALP: Week 20 (n=7)
    -21.1 ( 39.81 )
        ALP: Week 24 (n=7)
    20.7 ( 120.53 )
        ALP: Week 28 (n=6)
    153.8 ( 436.62 )
        ALP: Week 40 (n=7)
    -37.0 ( 44.79 )
        ALP: Week 52 (n=7)
    -6.4 ( 29.79 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: From screening (Day -30) up to Week 56; Serious and Non-serious AEs: From baseline (Day 1) up to Week 56
    Adverse event reporting additional description
    Safety analysis set included all participants who took at least 1 dose of study intervention.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Macitentan
    Reporting group description
    		 Participants 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.

    Serious adverse events
    		 Macitentan
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 7 (28.57%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia Bacterial
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metapneumovirus Infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Macitentan
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    General disorders and administration site conditions
    Catheter Site Dermatitis
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    4 / 7 (57.14%)
         occurrences all number
    6
    Respiratory, thoracic and mediastinal disorders
    Obstructive Sleep Apnoea Syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Nasal Obstruction
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Asthma
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    2
    Investigations
    Crystal Urine Present
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Post-Traumatic Neck Syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Head Injury
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Fall
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Arthropod Bite
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Congenital, familial and genetic disorders
    Ichthyosis
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Nervous system disorders
    Tongue Biting
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Iron Deficiency Anaemia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Neutropenia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Eye disorders
    Conjunctivitis Allergic
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Ocular Hyperaemia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Strabismus
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Diarrhoea
         subjects affected / exposed
    3 / 7 (42.86%)
         occurrences all number
    4
    Faeces Soft
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Haemorrhage Subcutaneous
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Dermatitis Allergic
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Acne
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Urticaria
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Miliaria
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Infections and infestations
    Viral Infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Streptococcal Infection
         subjects affected / exposed
    3 / 7 (42.86%)
         occurrences all number
    3
    Pneumonia Viral
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Pneumonia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Paronychia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Otitis Media
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    2
    Nasopharyngitis
         subjects affected / exposed
    6 / 7 (85.71%)
         occurrences all number
    24
    Adenovirus Infection
         subjects affected / exposed
    3 / 7 (42.86%)
         occurrences all number
    3
    Conjunctivitis
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Conjunctivitis Bacterial
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Herpes Virus Infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Nov 2021
    The reason for this protocol amendment was to clarify that the treatment of pulmonary arterial hypertension (PAH) worsening is not limited to a specific drug, but within the scope of routine clinical practice.
    25 Nov 2021
    The reason for this protocol amendment was to modify the amount of blood collected and to add time points for blood collection in pediatric participants < 2 years. Minor corrections and editorial revisions were also implemented.
    09 Mar 2022
    The reason for this protocol amendment was to change the inclusion/exclusion criteria, to update the method of administration and to modify the definition prohibited concomitant therapy. Minor corrections and editorial revisions were also implemented.
    09 Mar 2023
    The reason for this protocol amendment was to add allowance for Day 1 and to add interpretation of exclusion criteria, and to also allow for the use of local laboratory data for eligibility assessment. Minor corrections and editorial revisions were also implemented.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The interpretation of study results was limited by small sample size of only 7 participants. Study was not controlled, hence no comparison to Standard of Care (or placebo) was possible.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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