Pulmonary arterial hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: macitentan
Product Code: ACT-064992 / JNJ-67896062
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Con
Sponsors
ACTELION Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. To assess efficacy of macitentan in children with PAH.;Primary end point(s): In subjects = 2 years of age in the macitentan arm: • Trough (pre-dose) plasma concentrations of macitentan and its active metabolite(ACT-132 577) at Week 12 (steady-state) In subjects less than 2 years of age on macitentan: • Trough concentrations of macitentan and its active metabolite (ACT132577) at Week 4 (steady-state) ;Timepoint(s) of evaluation of this end point: At steady-state | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are listed below: • Time to first CEC-confirmed hospitalization for PAH occurring between randomization/Visit 2 and end of core period (EOCP). • Time to CEC-confirmed death due to PAH occurring between randomization/Visit 2 and end of core period (EOCP). • Time to death (all causes) occurring between randomization/Visit 2 and Study Closure. Following secondary endpoints are analyzed up to end of randomized macitentan or SoC + 7 days. Baseline is the last non-missing value observed before or on the day of randomization/ Visit 2 • WHO FC status (I or II vs III or IV) at Week 24. • Percent of Baseline plasma NT-proBNP at Week 24. • Change from Baseline to Week 48 in in mean daily time spent in moderate to vigorous physical activity as measured by accelerometry. • Change from Baseline to Week 24 in tricuspid annular plane systolic excursion (TAPSE), and left ventricular eccentricity index measured by echocardiography (centrally assessed). • Change from Baseline to Week 24 in Quality of Life as measured by the PedsQLTM 4.0 Generic Core Scales Short Form (SF15)1. ;Timepoint(s) of evaluation of this end point: Up to end of randomized treatment + 7 days | — |
Countries
Australia, Austria, Brazil, Canada, China, Colombia, Finland, France, Hungary, Israel, Korea, Republic of, Malaysia, Mexico, Philippines, Poland, Portugal, Russian Federation, South Africa, Spain, Thailand, Ukraine, United States, Viet Nam
Contacts
Public ContactClinical Registry group
Janssen-Cilag International NV
Outcome results
None listed