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
Sponsors
Janssen Pharmaceutical K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Japanese males or females between = 3 months and 4 Wood Units × 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. 4. WHO FC I to IV. 5. PAH-specific treatment-naïve patients or patients on PAH-specific treatment 6. A woman of childbearing potential must have a negative highly sensitive serum -human chorionic gonadotropin test at Screening and a negative urine pregnancy test at the first administration of study intervention. 7. A woman must be a. Not of childbearing potential b. Of childbearing potential and o Practicing a highly effective, preferably user-independent method of contraception (failure rate of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn. 2. Patients with PAH associated with open shunts, as specified below: a. Eisenmenger syndrome b. Moderate to large left-to-right shunts as judged by the investigator 3. Patients with the following congenital cardiac abnormalities: a. Cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, pulmonary atresia with ventricular septal defect, unless operatively repaired and with no residual shunt b. Univentricular heart and/or patients with Fontan-palliation 4. Patients with pulmonary hypertension due to lung disease (eg, bronchopulmonary dysplasia) 5 Patients with the following diseases: a. Patients with pulmonary vein stenosis b. Patients with bronchopulmonary dysplasia 6. Hemoglobin or hematocrit 3 × ULN at Screening. 8. Severe hepatic impairment, eg, Child-Pugh Class C, at Screening. 9. Clinical signs of hypotension which in the investigator’s judgment would preclude initiation of a PAH-specific therapy at Screening. 10. Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 at Screening. 11. Known concomitant life-threatening disease with a life expectancy <12 months. 12. Patients receiving PAH-specific treatments (excluding PDE-5 inhibitor) at the first administration of study intervention. 13. Start or change of dose* with PDE-5 inhibitor within 90 days before RHC at Screening (* Dose adjustments are permitted based on patient body-weight change). 14. Start or change of dose* of Calcium channel blockers and/or diuretics within 7 days before RHC (* Dose adjustments are permitted based on patient body-weight change). 15 Previous treatment* with macitentan at any time. 16. Any PAH-related surgical intervention planned, or patients listed for organ transplantation related to PAH. 17. Treatment with strong inducers of CYP3A4 (eg, rifabutin, rifampicin, carbamazepine, phenobarbital, phenytoin, St. John’s wort), within 4 weeks prior to the first administration of study intervention. 18. Systemic treatment with strong inhibitors of CYP3A4 (eg, clarithromycin, itraconazole, ketoconazole, nelfinavir, posaconazole, ritonavir, and voriconazole) within 4 weeks prior to the first administration of study intervention. 19. Systemic treatment with moderate dual CYP3A4/CYP2C9 inhibitor (eg, fluconazole and amiodarone), or administration of a combination of a moderate CYP3A4 inhibitor (eg, ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) together with a moderate CYP2C9 inhibitor (eg, miconazole) within 4 weeks prior to the first administration of study intervention. 20. Taken any disallowed therapies as noted in in the protocol before the planned first dose of study intervention. 21. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before the planned first dose of study intervention or is currently enrolled in an investigational study. 22. Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 weeks after the last dose of study intervention. 23. Any condition for which, in the opinion of the investigator, participation would not be in t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of macitentan on hemodynamic measures at Week 24;Secondary Objective: - To evaluate the effect of macitentan on pulmonary hemodynamic parameters other than PVRI at Week 24. - To evaluate the effect of macitentan on World Health Organization (WHO) Functional Class (FC) at Week 24 (For patients whose age is >4 years of age when initial informed consent) - To evaluate the effect of macitentan on Panama FC at Week 24#- To evaluate the effect of macitentan on exercise capacity at Week 24 (For patients who are developmentally able to understand and perform the 6-minute walk test [6MWT] and whose age is =6 years of age when initial informed consent) - To evaluate the effect of macitentan on NT-proBNP at Week 24 - To evaluate the effect of macitentan on Echocardiography at Week 24 - To evaluate the effect of macitentan on quality of life at Week 24 - To evaluate the effect of macitentan on physical activity at Week 24 (For patients whose age is =2 years of age when initial informed consent) ;Primary end point(s): Fold change at Week 24 in pulmonary vascular resistance index (PVRI);Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline to Week 24 in the following hemodynamic variables: pulmonary vascular resistance (PVR), mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), cardiac output (CO), total pulmonary resistance (TPR) and mixed venous oxygen saturation (SvO2) at rest. - Improvement in WHO FC from baseline to Week 24 (yes/no). - Improvement in Panama FC from baseline to Week 24 (yes/no). - Change from baseline to Week 24 in exercise capacity (6-minute walk distance [6MWD], as measured by the 6MWT). - Change from baseline to Week 24 in NT-proBNP. - Change from baseline to Weeks 24 in tricuspid annularplane systolic excursion (TAPSE) and left ventricular eccentricit y index measured b y echocardiography. - Change from baseline to Week 24 in: PedsQL™ 4.0 Generic Core Scales Short Form (SF-15). - Change from baseline to Week 24 in physical activity as measured by accelerometry. - Macitentan and aprocitentan concentrations in plasma or blood at all assessed timepoints. - Changes from baseline to all assessed timepoints in exercise capacity (6MWD, as measured by the 6MWT). - Change from baseline to all assessed timepoints indyspnea on exertion assessed by the Borg CR10 Scale® - Change from baseline to all assessed timepoints in physical activity as measured by accelerometry ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Japan
Contacts
Public ContactClinical Registry group
Janssen-Cilag International NV
Outcome results
None listed