A study to find out whether the medicine macitentan works in children with pulmonary arterial hypertension (PAH)

Phase 1

Conditions: Pulmonary arterial hypertension
MedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2016-001062-28-FI

Lead Sponsor: ACTELION Pharmaceuticals Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

1. 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.
2. Males or females between = 1 month and < 18 years of age.
3. Subjects with body weight = 3.5 kg at randomization.
4. PAH diagnosis, confirmed by historical RHC (mPAP = 25 mm Hg, and PAWP = 15 mm Hg, and PVRi > 3 WU x m2).
5. PAH belonging to the Nice 2013 Updated Classification Group 1 (including subjects with Down Syndrome) and of following etiologies:
• iPAH
• hPAH
• PAH associated with CHD
• Drug or toxin-induced PAH
• PAH associated with HIV
• PAH-aCTD
6. WHO FC I to III.
7. 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 EOS.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Subjects 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.
2. Subjects with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts.
3. Subjects with known diagnosis of bronchopulmonary dysplasia.
4. Subjects receiving a combination of > 2 PAH-specific treatments at randomization.
5. Treatment with IV or SC prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing.
6. In children = 2 y.o.: Previous treatment with macitentan at any time.
7. Systemic treatment with moderate dual CYP3A4/ CYP2C9 inhibitor (e.g. fluconazole and amiodarone), or administration of a combination of a moderate CYP3A4 (e.g. ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) together with a moderate CYP2C9 inhibitor (e.g. miconazole, piperine) within 4 weeks prior to randomization.
8. Hemoglobin or hematocrit <75% of the lower limit of normal range
9. Serum AST and/or ALT > 3 times the upper limit of normal range'
10. Pregnancy (including family planning) or breastfeeding.
11. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the PK of macitentan in children with PAH.;Secondary Objective: To assess safety and tolerability of macitentan in children with PAH.<br>To assess efficacy of macitentan in children with PAH.;Primary end point(s): In subjects = 2 years of age in the macitentan arm:<br>• Trough (pre-dose) plasma concentrations of macitentan and its active metabolite(ACT-132 577) at Week 12 (steady-state)<br>In subjects less than 2 years of age on macitentan:<br>• Trough concentrations of macitentan and its active metabolite (ACT-132577) at Week 4 (steady-state);Timepoint(s) of evaluation of this end point: At steady state

Secondary Outcome Measures

Name	Time	Method

Related Trials