The trial is taking place at:
C

CIMS Hospital | Research Department

Veeva-enabled site

Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (UNISUS)

Actelion Pharmaceuticals logo

Actelion Pharmaceuticals

Status and phase

Enrolling
Phase 3

Conditions

Pulmonary Arterial Hypertension

Treatments

Drug: Macitentan 75 mg
Drug: Macitentan 10 mg
Drug: Placebo
Drug: Macitentan 37.5 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT04273945
CR108740
AC-055-315 (Other Identifier)
2019-002533-11 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to demonstrate superiority of macitentan 75 milligrams (mg) in prolonging the time to the first clinical events committee (CEC)-adjudicated morbidity or mortality (M/M) event in participants with symptomatic pulmonary arterial hypertension (PAH) compared to macitentan 10 mg.

Enrollment

900 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

* 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 toxin-induced; 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

Exclusion criteria

* 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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

900 participants in 2 patient groups

Macitentan 10 milligrams (mg) + Placebo
Active Comparator group
Description:
Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (<) 10 milligrams (mg), or daily dose of bosentan <250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration.
Treatment:
Drug: Placebo
Drug: Macitentan 37.5 mg
Drug: Macitentan 10 mg
Drug: Macitentan 75 mg
Macitentan 75 mg + Placebo
Experimental group
Description:
Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan <10 mg, or a daily dose of bosentan <250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period.
Treatment:
Drug: Placebo
Drug: Macitentan 37.5 mg
Drug: Macitentan 10 mg
Drug: Macitentan 75 mg

Trial contacts and locations

273

Loading...

Central trial contact

Study Contact

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems