This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3 study with an open-label single-arm extension period to evaluate pharmacokinetics (PK), safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH).



Eligible Ages
Between 1 Month and 17 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Signed informed consent by the parent(s) or legally designated representative and assent from developmentally capable children prior to initiation of any study-mandated procedure - Males or females between greater than or equal to (>=) 1 month and less than (<) 18 years of age - Participants with body weight >= 3.5 kilograms (kg) at randomization - Pulmonary arterial hypertension (PAH) diagnosis confirmed by historical RHC (mPAP greater than or equal to [>=] 25 millimeters of mercury [mmHg], and Pulmonary artery wedge pressure [PAWP] less than or equal to [<=] 15 mmHg, and Pulmonary vascular resistance index [PVRi] greater than [>] 3 WU × m2), where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced by Left atrium pressure [LAP] or Left ventricular end diastolic pressure [LVEDP] (in absence of mitral stenosis) assessed by heart catheterization - PAH belonging to the Nice 2013 Updated Classification Group 1 (including participants with Down Syndrome) and of following etiologies: idiopathic PAH; heritable PAH; PAH associated with congenital heart disease (CHD); Drug or toxin induced PAH; PAH associated with HIV; PAH associated with connective tissue diseases (PAH-aCTD); and World health organization (WHO) Functional class I to III - Females of childbearing potential must have a negative pregnancy test at Screening and at Baseline, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) up to the end of study (EOS)

Exclusion Criteria

  • Participants with PAH due to portal hypertension, schistosomiasis, or with pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn - Participants with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts - Participants receiving a combination of > 2 PAH-specific treatments at randomization. - Treatment with intravenous (IV) or subcutaneous (SC) prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing - Hemoglobin or hematocrit <75 percent (%) of the lower limit of normal range - Serum Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) greater than (>) 3 times the upper limit of normal range - Pregnancy (including family planning) or breastfeeding. - Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol - Severe hepatic impairment, for example Child-Pugh Class C - Clinical signs of hypotension which in the investigator's judgment would preclude initiation of a PAH-specific therapy - Severe renal insufficiency (estimated creatinine clearance <30 mL/min or serum creatinine >221 micro-moles per liter [micro-mol/L]) - Participants with known diagnosis of bronchopulmonary dysplasia

Study Design

Phase 3
Study Type
Intervention Model
Parallel Assignment
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Macitentan is administered once daily via oral route. Children less than (<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those < 2 y.o.) or to the participant's body weight (for those greater than or equal to (>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit.
  • Drug: Macitentan
    Dispersible tablet; Oral use
    Other names:
    • ACT-064992
Standard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids.
  • Other: Standard-of-care
    Standard-of-care as per site's clinical practice which may comprise treatment with PAH non-specific treatment and/or up to two PAH-specific medications excluding macitentan and IV/SC prostanoids.

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Principal Investigator

More Details


Study Contact

Study Contact


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.