Health Condition 1: I270- Primary pulmonary hypertension
Conditions
Interventions
Intervention1: Macitentan Open Label: 10mg, Once daily, Oral, 4 weeks in run in period
Intervention2: Macitentan Double Blind: 10mg, Once daily, Oral, 4 years
Intervention3: Macitentan Double Blind: 3
Sponsors
Janssen Research & Development , LLC
Eligibility
Inclusion criteria
Inclusion criteria: 1 At least 18 years of age 2 Symptomatic PAH in WHO FC II, III, or IV 3 PAH subtype falling in one of the below classifications: 4 Idiopathic, heritable, drug- or toxin-induced, or related to connective tissue disease, HIV infection, portal hypertension, or congenital heart disease 5 Have a PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to screening: - Mean pulmonary artery pressure (mPAP) > 20 mm Hg, AND - Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) = 15 mm Hg, AND - Pulmonary vascular resistance (PVR) = 3 Wood Units (i.e., = 240 dyn•sec•cm-5) Additional criteria will be assessed at the screening visit.
Exclusion criteria
Exclusion criteria: 1 Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening, based on records that confirm documented medical history: - Body mass index (BMI) > 30 kg/m2 - Diabetes mellitus of any type - Essential hypertension (even if well controlled) - Coronary artery disease, i.e., any of the following: – History of stable angina, known more than 50% stenosis in a coronary artery, history of myocardial infarction, or history of or planned coronary artery bypass grafting and/or coronary artery stenting 2 Presence of moderate or severe obstructive or restrictive lung disease in patients with a known or suspected history of significant lung disease Additional criteria will be assessed at the screening visit. 3 Treatment with a strong CYP3A4 inducer (eg, rifabutin, rifampin, rifampicin, rifapentin, carbamazepine, phenobarbital, phenytoin, St. John’s Wort) within 1 month prior to randomization or start of run-in, if applicable 4 Treatment with a strong CYP3A4 inhibitor (eg, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) or a moderate dual CYP3A4/CYP2C9 inhibitor (eg, fluconazole, amiodarone) or coadministration of a combination of moderate CYP3A4 (eg, ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitors (eg, miconazole, piperine), in the 1-month period prior to randomization, or start of run-in, if applicable. External use (cream, shampoo, etc) per approved label is permitted. 5 Significant unrepaired structural left heart valvular disease (ie, moderate or severe aortic or mitral stenosis or regurgitation); pericardial constriction; restrictive or congestive left-sided cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction; or left ventricular outflow obstruction 6 Known or suspected pulmonary veno-occlusive disease (PVOD) 7 Permanent atrial fibrillation or atrial flutter, in the opinion of the investigator. 8 Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first CEC-adjudicated M/M event on-treatment (ie, up to 7 days after the last dose of double-blind (DB) study intervention), defined as time from randomization to the first of the following events: - All-cause death, including deaths caused by an on-treatment AE, that occur within 4 weeks of study DB treatment discontinuation - Non-planned PAH-related hospitalization (including for worsening of PAH, atrial septostomy, lung transplantation with or without heart transplantation, or initiation of parenteral prostacyclins) - PAH-related disease progression, defined as (both criteria must be satisfied): o Deterioration by at least 15% in exercise capacity, as measured by the 6-minute walk distance (6MWD), from baseline, confirmed by a second 6MWD test performed on a different day within 2 weeks of the initial test o Initiation of additional PAH therapy or Worsening of WHO FCTimepoint: At each study visits, monthly and at any time in case of event occurrence, until 217 M/M events are reached | — |
Secondary
| Measure | Time frame |
|---|---|
| 1 Change from baseline to Week 24 in 6MWD 2 Time to first occurrence of either death due to PAH or hospitalization for PAH, CEC adjudicated event on-treatment (ie, up to 7 days after the last dose of DB study intervention), as defined hereafter: - Death due to PAH, including deaths caused by on-treatment AE that occur within 4 weeks of study DB treatment discontinuation OR - Non-planned PAH-related hospitalization 3 Change from baseline to Week 24 in PAH-SYMPACT: - Cardiopulmonary symptom domain score - Cardiovascular symptom domain score 4 Time to death occurring between randomization and end of double blind treatment (EDBT) period as defined hereafter: - All-cause death, including all deaths occurring during the DB period regardless of potential discontinuation of study intervention or initiation or change in PAH medication.Timepoint: Screening, Day 1, Month 3, and all scheduled visits thereafter until EDBT or anytime in case of event, with the exception of PAH-SYMPACT | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czech Republic, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Republic of Korea, Russian Federation, Serbia, Singapore, Slovakia, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactDr Sanish Davis
Johnson & Johnson Pvt Ltd
Outcome results
None listed