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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Macitentan 10 mg; Drug: Macitentan 37.5 mg; Drug: Macitentan 75 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 935
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Sanatorio de la Trinidad Mitre
  • C.a.b.a., Argentina, C1180AAX
    • Sanatorio Güemes
  • Caba, Argentina, C1426ABP
    • Centro Médico Dra. De Salvo
  • Caba, Argentina, 1199ABB
    • Hospital Italiano de Buenos Aires
  • Caba, Argentina, C1048AAN
    • Sanatorio Ramon Cereijo
  • Corrientes, Argentina, W3400AMZ
    • Instituto de Cardiologia de Corrientes
  • Rosario, Argentina, 2000
    • Instituto Medico de la Fundacion Estudios Clinicos
  • Rosario, Argentina, S2000DSR
    • Instituto Cardiovascular de Rosario
• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Chermside, Australia, 4032
    • The Prince Charles Hospital
  • Darlinghurst, Australia, 2010
    • St Vincent's Hospital
  • Hobart, Australia, 7000
    • Royal Hobart Hospital
  • Murdoch, Australia, 6150
    • Fiona Stanley Hospital
  • Westmead, Australia, 2145
    • Westmead Hospital
• Austria
  • Graz, Austria, 8036
    • Lkh-Univ. Klinikum Graz
  • Linz, Austria, 4020
    • Ordensklinikum Linz GmbH Elisabethinen
  • Vienna, Austria, 1090
    • Medical University Vienna
• Belarus
  • Minsk, Belarus, 220036
    • The Republican Scientific-Practical Center ''Cardiology''
  • Minsk, Belarus, 220143
    • Minsk Regional Clinical Hospital
• Belgium
  • Brussels, Belgium, 1070
    • ULB Hopital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
• Brazil
  • Belo Horizonte, Brazil, 30441-070
    • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
  • Belo Horizonte, Brazil, 30130-100
    • Universidade Federal De Minas Gerais - Hospital das Clínicas
  • Brasília, Brazil, 70840-901
    • Empresa Brasileira de Servicos Hospitalares-EBSERH-Hospital Universitario de Brasilia
  • Campina Grande do Sul, Brazil, 83430-000
    • Sociedade Hospitalar Angelina Caron - Hospital Angelina Caron
  • Curitiba, Brazil, 80060-240
    • Ceti - Centro de Estudos Em Terapias Inovadoras
  • Florianópolis, Brazil, 88020-210
    • Ynova Pesquisa Clinica
  • Goiânia, Brazil, 74605-020
    • Universidade Federal de Goias - Hospital das Clinicas da UFG
  • Porto Alegre, Brazil, 90035-003
    • Hospital das Clinicas de Porto Alegre
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • Recife, Brazil, 50070-902
    • Instituto de Medicina Integral Professor Fernando Figueira
  • Santo André, Brazil, 09060 870
    • Fundacao do ABC Centro Universitario FMABC
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da USP
  • São Paulo, Brazil, 04012-909
    • Secretaria de Estado da Saude Instituto Dante Pazzanese de Cardiologia
• Bulgaria
  • Sofia, Bulgaria, 1309
    • Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
  • Sofia, Bulgaria, 1750
    • University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Health Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5G2C4
      • University Health Network - Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• China
  • Beijing, China, 100029
    • Beijing Anzhen Hospital
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100020
    • Beijing Chaoyang Hospital
  • Changsha, China, 410011
    • The Second Xiangya Hospital of Central South Hospital
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400016
    • The First Affiliated Hospital of Chongqing Medical University
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Shanghai, China
    • Zhongshan Hospital Fudan University
  • Shanghai, China, 201112
    • RenJi Hospital
  • Shenyang, China, 110000
    • The General Hospital of Northern Theater Command
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiaotong University
• Colombia
  • Bogotá, Colombia, 1101131
    • Fundación Neumologica Colombiana
  • Bucaramanga - Piedecuesta - Valle de Menzuli, Colombia, 6810002
    • Fundacion cardiovascular de Colombia
  • Cali, Colombia, 760042
    • Clínica Imbanaco S.A.S.
  • Medellín, Colombia, 681004
    • Centro Cardiovascular Colombiano Clínica Santa María
  • Soledad, Colombia, 0000000
    • Hospital Universidad del Norte
• Czechia
  • Prague, Czechia, 128 08
    • General University Hospital II.department of Internal Medicine-cardiology and angiology
• Denmark
  • Aarhus, Denmark, 8200
    • Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
• France
  • Brest, France, 29200
    • CHU de Brest - Hopital de la Cavale Blanche
  • Caen, France
    • Hôpital Côte De Nacre
  • Le Kremlin-Bicêtre, France, 94270
    • Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
  • Lille, France
    • CHRU de Lille Hopital Claude Huriez
  • Marseille, France, 13915
    • APHM - Hopital Nord
  • Nice, France, 06002
    • Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
  • Saint-Priest-en-Jarez, France, 42277
    • CHU Saint Etienne Hopital Nord
  • Toulouse, France
    • Hopital Larrey CHU de Toulouse
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Ruhr Universitat Bochum Diabeteszentrum
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • München, Germany, 81377
    • Medizinische Klinik und Poliklinik V Klinikum Grosshadern der LMU
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg
• Greece
  • Alexandroupoli, Greece, 681 00
    • University Hospital of Alexandroupolis
  • Athens, Greece, 11528
    • Alexandra General Hospital of Athens
  • Larissa, Greece, 41334
    • University Hospital of Larissa
  • Thessaloniki, Greece, 54636
    • AHEPA University General Hospital of Thessaloniki
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem,Pulmonológiai Klinika
  • Budapest, Hungary, 1096
    • Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
• India
  • Ahmedabad, India, 380006
    • NHL Medical College (SVP Hospital IMSR)
  • Ahmedabad, India, 381060
    • CIMS Hospital
  • Bangalore, India, 560099
    • Narayana Hrudayalaya Limited
  • Chengalpetu, India, 603203
    • SRM Medical College Hospital & Research Centre
  • Coimbatore, India, 64103
    • Govindaswamy Kuppuswamy Naidu Memorial Hospital
  • Durgapur, India, 713216
    • Healthworld hospitals
  • Hyderabad, India, 500034
    • Renova Century Hospitals
  • Hyderbad, India, 500034
    • Care Hospitals
  • Kolkata, India, 700099
    • Rabindranath Tagore International Institute of Cardiac Sciences
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
  • New Delhi, India, 110002
    • GB Pant Institute of Post Graduate Medical Education & Research
  • Puducherry, India, 605008
    • Jawaharlal Institute Of Postgraduate Medical Education And Research
  • Surat, India, 395001
    • B.D. Mehta Mahavir Heart Institute
• Israel
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Litwinsky, Israel, 5265601
    • The Chaim Sheba Medical Center
  • Ẕerifin, Israel, 70300
    • Yitzhak Shamir Medical Center
• Italy
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41125
    • AOU Di Modena Policlinico Di Modena
  • Nuoro, Italy, 08100
    • Ospedale San Francesco
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Pisa, Italy, 56124
    • Fondazione Toscana Gabriele Monasterio CNR
  • Roma, Italy, 00168
    • Policlinico Gemelli Universita Cattolica
• Japan
  • Bunkyō City, Japan, 113-8655
    • The University of Tokyo Hospital
  • Fukuoka, Japan, 812 8582
    • Kyushu University Hospital
  • Hiroshima, Japan, 737-8505
    • Kure Kyosai Hospital
  • Kagoshima, Japan, 890 8520
    • Kagoshima University Hospital
  • Kanagawa, Japan, 216 8511
    • St Marianna University Hospital
  • Kanazawa, Japan, 920 8641
    • Kanazawa University Hospital
  • Kobe, Japan, 650 0017
    • Kobe University Hospital
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Kyoto, Japan, 606 8507
    • Kyoto University Hospital
  • Matsumoto, Japan, 390 8621
    • Shinshu University Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya, Japan, 467 8602
    • Nagoya City University Hospital
  • Nagoya, Japan, 466 8560
    • Nagoya University Hospital
  • Niigata, Japan, 951 8520
    • Niigata University Medical And Dental Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Okayama, Japan, 700 8558
    • Okayama University Hospital
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Sapporo, Japan, 060 8543
    • Sapporo Medical University Hospital
  • Suita-Shi, Japan, 564-8565
    • National Cerebral and Cardiovascular Center
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Tsukuba, Japan, 305 8576
    • University of Tsukuba Hospital
• Malaysia
  • George Town, Malaysia, 10990
    • Hospital Pulau Pinang
  • Kajang, Malaysia, 43000
    • Hospital Serdang
  • Kota Samarahan, Malaysia, 94300
    • Sarawak Heart Center
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara (National Heart Institute)
• Mexico
  • Guadalajara, Mexico, 44657
    • Consultorio Privado del Dr. Gabriel Arturo Ramos Lopez
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiologia Dr. Ignacio Chavez
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
  • Monterrey, Mexico, 64718
    • Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
  • Morelia, Mexico, 58260
    • Centro de Investigación Clinica Chapultepec
  • México, Mexico, 52787
    • Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VUMC Amsterdam
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis Nieuwegein
  • Nijmegen, Netherlands, 6525 GA
    • Radboud Umcn
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus MC
• Norway
  • Nordbyhagen, Norway, 1478
    • Akershus Universitetssykehus
  • Oslo, Norway, 372
    • Oslo University Hospital
• Poland
  • Bialystok, Poland, 15 276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
  • Gdansk, Poland, 80214
    • Uniwersyteckie Centrum Kliniczne
  • Katowice, Poland, 40 635
    • SPSK nr 7 SUM w Katowicach Gornoslaskie Centrum Medyczne im Prof Leszka Gieca
  • Krakow, Poland, 31 202
    • Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
  • Szczecin, Poland, 70 111
    • Uniwersytecki Szpital Kliniczny Nr 2 PUM w Szczecinie
  • Warsaw, Poland, 02 507
    • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji
  • Wroclaw, Poland, 51 124
    • Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo Rozwojowy
• Portugal
  • Coimbra, Portugal, 3004 561
    • Uls Coimbra - Hosp. Univ. Coimbra
  • Lisbon, Portugal, 1169-024
    • Uls Sao Jose - Hosp. Santa Marta
  • Lisbon, Portugal, 1769-001
    • Uls Santa Maria - Hosp. Pulido Valente
• Russia
  • Barnaul, Russia, 656055
    • Altay Regional Cardiological Dispensary
  • Chelyabinsk, Russia, 454076
    • Chelyabinsk Regional Clinical Hospital
  • Kazan', Russia, 420101
    • State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'
  • Kemerovo, Russia, 650002
    • Scientific and Research Institution of Cardiovascular Diseases Complex Problems
  • Moscow, Russia, 121309
    • Moscow City Clinical Hospital No.51
  • Moscow, Russia, 121552
    • National Medical Research Center of Cardiology of MoH of Russian Federation
  • Saint Petersburg, Russia, 197341
    • National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
  • Samara, Russia, 443070
    • Samara Regional Clinical Cardiological Dispensary
  • Tyumen, Russia, 625032
    • State Autonomous Healthcare Institution of Tyumen Region 'Scientific and Practical Medical Center'
  • Volgograd, Russia, 400008
    • Volgograd Regional Clinical Cardiology Center
• Saudi Arabia
  • Riyadh, Saudi Arabia, 59046
    • King Fahad Medical City
  • Riyadh, Saudi Arabia, 11564
    • King Faisal Specialist Hospital & Research Center
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia
  • Kamenitz, Serbia, 21204
    • Institute for Pulmonary Disease of Vojvodina
• Singapore
  • Singapore, Singapore, 119228
    • National University Heart Centre, Singapore
  • Singapore, Singapore, 169609
    • National Heart Centre (NHC) Singapore
• Slovakia
  • Bratislava, Slovakia, 833 48
    • Narodny ustav srdcovych a cievnych chorob
  • Košice, Slovakia, 040 11
    • The Eastern Slovakia Institute of Cardiovascular Diseases
• South Africa
  • Johannesburg, South Africa
    • Milpark Hospital
  • Lenasia, South Africa, 1820
    • Dr Kalla
• South Korea
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 3080
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 8003
    • Hosp. Del Mar
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Málaga, Spain, 29603
    • Hosp. Costa Del Sol
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska Universitetsjukhuset
  • Lund, Sweden, 221 85
    • Skanes universitetssjukhus
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital Mahidol University
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital and Medical College
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital Mahidol University
  • Chiang Mai, Thailand, 50020
    • Maharaj Nakorn Chiang Mai hospital Faculty of Medicine
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Khon Kaen University
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01170
    • Adana City Hospital
  • Adana, Turkey (Türkiye), 01790
    • Cukurova University Medical Faculty
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Medical Faculty
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Sehir Hastanesi
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06170
    • Ankara Etlik Speciality Hospital
  • Antalya, Turkey (Türkiye), 07059
    • Akdeniz University Medical Faculty
  • Bursa, Turkey (Türkiye), 16310
    • Bursa Yuksek Ihtisas Training and Research Hospital
  • Denizli, Turkey (Türkiye), 20160
    • Pamukkale Universitesi Tip Fakultesi Hastanesi
  • Istanbul, Turkey (Türkiye), 34899
    • Marmara University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34668
    • Siyami Ersek Training and Research Hospital
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Tip Fakultesi Hastanesi
  • Izmir, Turkey (Türkiye), 35330
    • Dokuz Eylul Universitesi Tip Fakultesi Hastanesi
  • Izmir, Turkey (Türkiye), 35020
    • SBU Izmir Tepecik Egitim Ve Arastirma Hastanesi
  • Kartal Istanbul, Turkey (Türkiye), 34865
    • Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştirma Hastanesi
  • Mersin, Turkey (Türkiye), 33110
    • Mersin University Medical Faculty
• Ukraine
  • Cherkassy, Ukraine, 18000
    • CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
  • Cherkasy, Ukraine, 18009
    • Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
  • Dnipro, Ukraine, 49070
    • MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
  • Kharkiv, Ukraine, 61176
    • CNE' City Clinical Hospital #8' of Kharkiv City Council
  • Kyiv, Ukraine, 03680
    • State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
  • Kyiv, Ukraine, 02000
    • SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
  • Lviv, Ukraine, 79010
    • Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'
  • Ternopil, Ukraine, 46002
    • Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
• United Kingdom
  • London, United Kingdom, Nw3 2QG
    • Royal Free Hospital
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
    • Scottsdale, Arizona, United States, 85258
      • Arizona Pulmonary Specialists, Ltd
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital
    • Los Angeles, California, United States, 90033
      • USC Keck
    • Santa Barbara, California, United States, 93105
      • Jeffrey S. Sager, MD Medical Corporation
    • Torrance, California, United States, 90502-2006
      • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Weston, Florida, United States, 33331 3609
      • Cleveland Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Medical Group, Inc.
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University Of Iowa - Hospitals & Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70112 7021
      • Louisiana State University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5000
      • University of Michigan
    • Troy, Michigan, United States, 53215
      • Troy Beaumont
  • Missouri
    • St Louis, Missouri, United States, 63110-1032
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63110
      • Saint Louis University Academic Pavillion
  • Nebraska
    • Omaha, Nebraska, United States, 68198-2265
      • University of Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89511
      • Reno Heart Institute
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10029
      • Mount Sinai
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710-4000
      • Duke
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Lindner Clinical Trial Center/Christ Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Office
  • Oregon
    • Portland, Oregon, United States, 97239-3011
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97220-9442
      • The Oregon Clinic
    • Portland, Oregon, United States, 97225-6652
      • Oregon Pulmonary Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-5545
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital of Research
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine (BCM) - Baylor Heart Clinic
    • Plano, Texas, United States, 75093
      • Baylor Scott White - Plano
    • San Antonio, Texas, United States, 78229-3771
      • San Antonio Methodist TX Transplant Physicians Group
  • Vermont
    • Burlington, Vermont, United States, 05405
      • The Robert Larner, M.D. College of Medicine at The University of Vermont
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
• Vietnam
  • Hanoi, Vietnam
    • Hanoi Medical University Hospital
  • Ho Chi Minh City, Vietnam, 700000
    • University Medical Center Ho Chi Minh City
  • Ho Chi Minh City, Vietnam, 700000
    • Cho Ray Hospital
  • Ho Chi Minh City, Vietnam, 700000
    • Tam Anh Hospital
  • Ho Chi Minh City, Vietnam, 700000
    • Tam Duc Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Macitentan 10 milligrams (mg) + Placebo; 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.	Drug: Macitentan 10 mg; Participants will receive macitentan 10 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Macitentan 37.5 mg; Participants will receive macitentan 37.5 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Macitentan 75 mg; Participants will receive macitentan 75 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Placebo; Participants will receive matching placebo film-coated tablets orally.
Experimental: Macitentan 75 mg + Placebo; 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.	Drug: Macitentan 10 mg; Participants will receive macitentan 10 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Macitentan 37.5 mg; Participants will receive macitentan 37.5 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Macitentan 75 mg; Participants will receive macitentan 75 mg film-coated tablets orally.; Other Names: JNJ-67896062; Drug: Placebo; Participants will receive matching placebo film-coated tablets orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Treatment Period: Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or Mortality (M/M) Events	Time to first CEC-adjudicated M/M event on-treatment (ie.,up to 7 days after last dose of DB study intervention) is defined as time from randomization to first of following events: All-cause death, including death caused by on-treatment adverse event that occur within 4 weeks of study DB treatment discontinuation;non-planned Pulmonary Arterial Hypertension(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 worsening of World Health Organization(WHO) Functional Class(FC) from baseline or deterioration by at least 15% in exercise capacity, as measured by 6-minute walk distance(6MWD), from baseline and confirmed by second 6MWD test performed on different day within 2 week of initial test or appearance or worsening of signs or symptoms of right-sided heart failure that require initiation of intravenous diuretics.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Treatment Period: Change From Baseline to Week 24 in 6MWD	The 6MWT is a non-encouraged test performed to quantify exercise tolerance and capacity. This standardized test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.	Baseline up to Week 24
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score	The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH symptoms and impact questionnaire (PAH-SYMPACT) is completed daily for a 7-day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items.	Baseline up to Week 24
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiovascular Symptom Domain Score	The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT is completed daily for a 7 day period. The recall period of symptom items is the last 24 hours. An average cardiovascular symptoms domain score is determined based on the daily scores of the 5 items.	Baseline up to Week 24
Double-blind Treatment Period: Time to Death Occurring Between Randomization and End of Double-blind Treatment (EDBT)	Time to death occurring between randomization and EDBT will be reported.	Up to 4 years
Treatment Extension Period: Time to Death Occurring Between Randomization and End of Study (EOS)	Time to death occurring between randomization and EOS will be reported.	Up to 6 years
Double-blind Treatment Period: Number of Participants with CEC-adjudicated Death due to PAH and/or Hospitalizations for PAH (First and Recurrent) Events on-treatment	Number of Participants with CEC-adjudicated death or hospitalization due to PAH will be reported.	Up to 4 years

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Actelion Clinical Trials, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): October 7, 2025
• Study Completion (Estimated): February 20, 2029

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Molecular Mechanisms of Pharmacological Action; Endothelin A Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin B Receptor Antagonists; macitentan
• Other Study ID Numbers: CR108740; 2019-002533-11 (EudraCT Number); AC-055-315 (Other Identifier: Janssen Research & Development, LLC); 2024-515669-32-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No