A Phase 3, Prospective, Multicenter, Double-blind, Double-dummy, Randomized, Active-controlled, Parallel-group, Group-sequential, Adaptive, Event-driven Study to Compare Efficacy, Safety, and Tolerability of Macitentan 75 mg Versus Macitentan 10 mg in Patients with Pulmonary Arterial Hypertension, Followed by an Open-label Treatment Period With Macitentan 75 mg
- Conditions
- Pulmonary Hypertension10037454
- Registration Number
- NL-OMON54353
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
- Target population: greater than or equal to (><=) 18 (or the legal age of
consent in the jurisdiction in which the study is taking place) years of age
- Target population: Symptomatic Pulmonary Arterial Hypertension (PAH) in World
Health Organization,Functional Class (WHO FC) II, III, or IV
- Target population: PAH subtype falling in one of the below classifications:
Idiopathic; Heritable; Drug- or toxininduced; Related to: Connective tissue
disease, HIV infection, Portal hypertension, and Congenital heart disease with
small/coincidental cardiac defect with systemic-to-pulmonary shunt (for example
atrial septal defect, ventricular septal defect, patent ductus arteriosus,
atrioventricular septal defect) which does not account for the elevated
pulmonary vascular resistance (PVR) or persistent PAH documented by an Right
heart catheterization (RHC) ><= 1 year after simple systemic-to pulmonary shunt
repair
- PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior
to screening: Mean pulmonary artery pressure (mPAP) greater than (>) 20
millimeters of mercury (mm Hg), and; Pulmonary artery wedge pressure (PAWP) or
left ventricular end diastolic pressure (LVEDP) less than or equal to (<<=) 15
mm Hg, and PVR ><= 3 Wood Units (that is, ><= 240 dyn*sec/cm^5)
- Able to perform the 6-minute walking test (6MWT) with a minimum distance of
50 meters (m) and maximum distance of 440m at screening. Participants able to
walk more than 440m at screening are eligible if they are in WHO FC III or IV
and n-terminal prohormone of brain natriuretic peptide or n-terminal pro B-type
natriuretic peptide (NT-proBNP) level is ><=300 nanograms per liter (ng/L) at
screening, based on central laboratory results
- 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 kilograms per
meter square (kg/m^2), Diabetes mellitus of any type, Essential hypertension
(even if well controlled); Coronary artery disease, that is, any of the
following: history of stable angina, or known more than 50 percent (%) stenosis
in a coronary artery, or history of myocardial infarction, or history of or
planned coronary artery bypass grafting and/or coronary artery stenting
- Presence of moderate or severe obstructive lung disease (forced expiratory
volume in 1 second [FEV1] / forced vital capacity [FVC] < 70%; and FEV1 < 60%
of predicted after bronchodilator administration) ) in participants with a
known or suspected history of significant lung disease as documented by a
spirometry test performed within 1 year prior to screening
- Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or
C, based on records that confirm documented medical history
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
> 1.5*upper limit of normal (ULN) at screening
- Hemoglobin < 100 gram per liter (g/L) (< 10 gram per deciliter [g/dL]) at
screening
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Double-blind Treatment Period:<br /><br>Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or<br /><br>Mortality (M/M) Events.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Double-blind Treatment Period: Change From Baseline to Week 24 in 6MWD<br /><br><br /><br>Double-blind Treatment Period: Time to First occurrence of either<br /><br>CEC-adjudicated Death or Hospitalization due to PAH<br /><br><br /><br>Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms<br /><br>Based on PAH-SYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score<br /><br><br /><br>Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms<br /><br>Based on PAH-SYMPACT Questionnaire- Cardiovascular Symptom Domain Score<br /><br><br /><br>Double-blind Treatment Period: Time to Death Occurring Between Randomization<br /><br>and End of Double-blind Treatment (EDBT)<br /><br><br /><br>Treatment Extension Period: Time to Death Occurring Between Randomization and<br /><br>End of Study (EOS)</p><br>