A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
Study Purpose
The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years - 80 Years |
| Gender | All |
Inclusion Criteria:
- - Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization [WHO] Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA) - 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT).
- - World Health Organization functional class (WHO FC) >= II.
- - Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable.
Exclusion Criteria:
- - Acute pulmonary embolism within 3 months prior to or during Screening.
- - Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the double-blind period.
- - Significant obstructive and restrictive lung disease.
- - Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
- - Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the fixed duration part of the study.
- - Decompensated cardiac failure if not under close supervision.
- - Known and documented life-threatening cardiac arrhythmias.
- - Acute myocardial infarction within 6 months prior to, or during Screening.
- - Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening.
- - Known or suspicion of pulmonary veno-occlusive disease (PVOD) - Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization.
- - Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral, inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin receptor agonists or riociguat, a) within 90 days prior to Randomization, or b) anticipated during the fixed duration part of the double-blind [DB] period.
- - Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.
- - Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 milliliters per minute per 1.73 meter square (mL/min/1.73 m^2) using the Chronic Kidney Disease Epidemiology Collaboration formula at 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) greater than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT04271475 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Actelion |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Actelion Clinical Trial |
| Principal Investigator Affiliation | Actelion |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
| Overall Status | Active, not recruiting |
| Countries | Argentina, Australia, Austria, Bulgaria, Canada, China, Colombia, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Chronic Thromboembolic Pulmonary Hypertension |
CTEPH is one of the leading causes of severe pulmonary hypertension (PH), classified within World Health Organization (WHO) group 4 PH. It is a rare, progressive pulmonary vascular disease that if left untreated, leads to progressively increasing pulmonary vascular resistance (PVR) and eventually right ventricle failure and death. Histopathologic findings including endothelial cell dysfunction and distal pulmonary arterial remodeling are shared between PAH and CTEPH, and PH-specific therapies (that is, riociguat) have shown efficacy in inoperable and persistent/recurrent CTEPH. The endothelin receptor antagonist macitentan offers a different mode of action and addresses an important unmet medical need for an alternative treatment option in this indication. This study will assess the effect of macitentan 75 mg on exercise capacity in CTEPH. The total duration of the study is approximately 6 years. The study comprises of a screening period (at least 14 days and up to 60 days), a double-blind (DB) treatment period (28 weeks [minimum duration] up to 3.5 years), an open-label (OL) extension period (starts at end-of-DB-treatment [EODBT] and will end for all participants 104 weeks after the last participant has completed DB Week 28). The DB period consists of an 8-week up-titration phase and a maintenance phase. The maintenance phase is divided into a 28-week fixed duration part, at the end of which primary endpoint is assessed, and a variable duration part. The duration of the DB period for an individual participant depends on the timepoint of entry into the study and whether a CEC-confirmed clinical worsening event occurred. Participants who discontinue DB study intervention during the 28-week fixed duration part will be followed until Week 28 in a post-treatment observation period (PTOP).
Arms
Experimental: Macitentan
Participant will receive macitentan at a dose of 10 milligram (mg) once daily (OD) for 4 weeks, followed by a dose of macitentan 37.5 mg for another 4 weeks and continue with the target dose of macitentan 75 mg. Participants who have reached the target dose of 75 mg, completed the Double-blind (DB) period up to Week 28 (either on treatment or in Post-treatment observation period [PTOP]) at minimum, may be eligible for transitioning into the Open label (OL) extension period once all participants have completed the DB part of the study, or earlier if they experienced a Clinical event committee (CEC) confirmed clinical worsening event.
Experimental: Placebo
Participants will receive placebo tablets matching the macitentan 10 mg, macitentan 37.5mg and macitentan 75 mg tablets, respectively. Participants who completed the DB period as per protocol either on treatment or in PTOP are eligible for transitioning to the OL extension period and will receive macitentan 75 mg after an 8-week double-dummy uptitration (macitentan 10 mg for 4 weeks, followed by 37.5 mg for another 4 weeks).
Interventions
Drug: - Macitentan
Participants will receive Macitentan film-coated tablets orally od.
Drug: - Placebo
Participant will receive matching placebo tablets orally od.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
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University of California San Diego Medical Center
La Jolla, California, 92037
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Keck School of Medicine of USC
Los Angeles, California, 90033
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UC Davis Medical Center
Sacramento, California, 95817-2201
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University of Colorado - Anschutz Medical Campus
Aurora, Colorado, 80045
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Yale University School Of Medicine
New Haven, Connecticut, 06519
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University of Florida Health Jacksonville
Gainesville, Florida, 32608
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Piedmont Healthcare
Atlanta, Georgia, 30309
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Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
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Indiana University
Indianapolis, Indiana, 46202
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University of Kansas Medical Center
Kansas City, Kansas, 66160
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University of Maryland
Baltimore, Maryland, 21201
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Massachusetts General Hospital
Boston, Massachusetts, 02114
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Tufts Medical Center
Boston, Massachusetts, 21118
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University of Nebraska Medical Center
Omaha, Nebraska, 68198-2265
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VA Sierra Nevada Health Care System
Reno, Nevada, 89509
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University of New Mexico School of Medicine
Albuquerque, New Mexico, 87131
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Syracuse VA Medical Center
Syracuse, New York, 13210
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Cleveland Clinic
Cleveland, Ohio, 44195
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Legacy Hospital
Portland, Oregon, 97210
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University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
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Baylor Scott White - Plano
Plano, Texas, 75093
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Intermountain Medical Center
Murray, Utah, 84107
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University of Utah Cardiovascular Center
Salt Lake City, Utah, 84132
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University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792-2442
International Sites
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Sanatorio de la Trinidad Mitre
Buenos Aires, , C1039AAO
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Sanatorio Guemes
C.a.b.a., , C1180AAX
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Nexo Salud Investigacion Clinica
Ciudad Autonoma de Buenos Aires, , C1006ACC
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Queensland Lung Transplant Service
Chermside, , 4032
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St Vincent's hospital
Darlinghurst, , 2010
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LKH-Univ. Klinikum Graz
Graz, , 8036
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Ordensklinikum Linz GmbH Elisabethinen
Linz, , 4020
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Medizinische Universität Wien
Vienna, , 1090
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Military Medical Academy
Sofia, , 1606
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University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
Sofia, , 1750
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University Of Calgary - Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
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University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
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University Health Network - Toronto General Hospital
Toronto, Ontario, M5G 2N2
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Beijing Chaoyang Hospital
Beijing, , 100020
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Beijing Anzhen Hospital
Beijing, , 100029
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China-Japan Friendship Hospital
Beijing, , 100029
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Beijing Shijitan Hospital
Beijing, , 100038
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The First Affiliated Hospital of Chongqing Medical University
Chongqing, , 400016
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The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, , 510140
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Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, , 310016
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Zhongda Hospital,Southeast University
Nanjing, , 210009
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The Affiliated Hospital of Medical College Qingdao University
Qingdao, , 266003
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Huashan Hospital of Fudan University
Shanghai, , 200040
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Shanghai Pulmonary Hospital
Shanghai, , 200433
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Zhongshan Hospital,Fudan University
Shanghai, ,
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The General Hospital of Northern Theater Command
Shenyang, , 110000
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Tianjin Medical University General Hospital
Tian Jin, , 300052
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The First Affiliated Hospital of Xi'an Jiaotong University
Xi'An, , 710061
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Fundacion Neumologica Colombiana
Bogota, , 1101131
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Fundación Abood Shaio
Bogota, , 85369
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Clínica Imbanaco S.A.S.
Cali, , 760042
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Centro Cardiovascular Colombiano Clínica Santa María
Medellin, , 681004
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General University Hospital II.department of Internal Medicine-cardiology and angiology
Praha 2, , 128 08
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Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
Aarhus N, , 8200
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CHU de Brest - Hôpital de la Cavale Blanche
Brest, , 29200
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CHU de Grenoble - Hopital Albert Michallon
Grenoble Cedex 9, , 38043
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Hopital Bicêtre - Aphp Hôpitaux Universitaires Paris-Sud
Le Kremlin-Bicetre Cedex, , 94275
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Hôpital Cardiologique - Chru Lille
Lille Cedex, , 59037
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Address
CHU de Montpellier - Arnaud de Villeneuve
Montpellier, , 34295
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CHU Saint-Etienne - Hopital Nord
St Priest en Jarez Cedex, , 42277
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Hopital Larrey CHU de Toulouse
Toulouse Cedex 9, ,
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CHU de Nancy - Hopital de Brabois
Vandoeuvre les Nancy Cedex, , 54511
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Universitatsklinikum Bonn
Bonn, , 53127
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Medizinische Fakultat Carl Gustav Carus Technische Universitat Dresden
Dresden, , 01307
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Universitaetsklinikum Giessen
Giessen, , 35392
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Universitaetsklinikum Hamburg Eppendorf
Hamburg, , 20246
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Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie
Hannover, , 30625
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Thoraxklinik Heidelberg
Heidelberg, , 69126
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Universitaetsklinikum des Saarlandes
Homburg, , 66421
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Universitätsklinikum Jena
Jena, , 07747
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Krankenhaus Neuwittelsbach
München, , 80639
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Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
Budapest, , 1096
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Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
Szeged, , 6720
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Tel Aviv Medical Center
Tel Aviv, , 6423906
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The Chaim Sheba Medical Center
Tel-Hashomer, , 5265601
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Ospedale SS. Annunziata
Chieti, , 66100
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Fondazione IRCCS Policlinico San Matteo
Pavia, , 27100
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Fondazione Toscana Gabriele Monasterio CNR
Pisa, , 56124
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Policlinico Gemelli Universita Cattolica
Roma, , 00168
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A.O.U. Città della Salute e della Scienza
Torino, , 10126
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The University of Tokyo Hospital
Bunkyo, , 113-8655
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Kyushu University Hospital
Fukuoka, , 812-8582
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Kure Kyosai Hospital
Hiroshima, , 737-8505
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St.Marianna University Hospital
Kanagawa, , 216-8511
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Kobe University Hospital
Kobe, , 650-0017
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University Hospital Kyoto Perfectural University of Medicine
Kyoto, , 602-8566
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Kyoto University Hospital
Kyoto, , 606-8507
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Shinshu University Hospital
Matsumoto, , 390-8621
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Toho University Medical Center, Ohashi Hospital
Meguro-ku, , 153-8515
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Kyorin University Hospital
Mitaka, , 181-8611
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Nagoya University Hospital
Nagoya, , 466-8560
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National Hospital Organization Okayama Medical Center
Okayama, , 701-1192
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Hokkaido University Hospital
Sapporo-shi, , 060-8648
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National Cerebral and Cardiovascular Center
Suita-Shi, , 564-8565
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Juntendo University Hospital
Tokyo, , 113-8431
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University of Tsukuba Hospital
Tsukuba-City, , 305-8576
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Pusan National University Hospital
Busan, , 49241
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Seoul National University Hospital
Seoul, , 03080
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Asan Medical Center
Seoul, , 05505
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Samsung Medical Center
Seoul, , 06351
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The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, , 06591
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Lietuvos sveikatos mokslų universiteto ligoninė Kauno klinik
Kaunas, , 50161
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Vilnius University Hospital Santariskiu Klinikos
Vilnius, , LT-08661
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Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Ciudad De México, , 14080
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Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
Mexico, , 52787
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Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
Monterrey, , 64718
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Centro de Investigacion Clinica Chapultepec
Morelia, , 58260
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CRI Centro Regiomontano de Investigacion SC
Nuevo Leon, , 64060
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Krakowski Szpital Specjalistyczny im Jana Pawla II
Kraków, , 31-202
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Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego, PZOZ
Lublin, , 20-708
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Europejskie Centrum Zdrowia Otwock Sp. z o.o
Otwock, , 05-400
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Hosp. Garcia de Orta
Almada, , 2805-267
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Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu Sectia cardiologie III
Bucuresti, , 022328
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Spitalul Clinic Judetean de Urgenta
Tg. Mures, , 540136
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State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'
Kazan, , 420101
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Moscow City Clinical Hospital No.51
Moscow, , 121309
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National Medical Research Center of Cardiology of MoH of Russian Federation
Moscow, , 121552
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National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
Saint-Petersburg, , 197341
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Volgograd Regional Clinical Cardiology Center
Volgograd, , 400008
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King Faisal Specialist Hospital & Research Center
Riyadh, , 12713
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King Fahad Medical City
Riyadh, , 59046
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University Clinical Center of Serbia
Belgrade, , 11000
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Institute for Pulmonary Disease of Vojvodina
Sremska Kamenica, , 21204
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National University Heart Centre, Singapore
Singapore, , 119228
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National Heart Centre (NHC) Singapore
Singapore, , 169609
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Narodny ustav srdcovych a cievnych chorob
Bratislava, , 833 48
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Hosp. Clinic de Barcelona
Barcelona, , 08036
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Hosp. Univ. 12 de Octubre
Madrid, , 28041
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Hosp. Univ. La Paz
Madrid, , 28046
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Hosp. Virgen de La Victoria
Málaga, , 29010
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Hosp. Gral. Univ. de Toledo
Toledo, , 45007
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Kaohsiung Veterans General Hospital
Kaohsiung, , 813
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National Taiwan University Hospital
Taipei, , 10002
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Taipei Veterans General Hospital
Taipei, , 112
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Chang-Gung Memorial Hospital, LinKou Branch
Taoyuan, , 333
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Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, , 50200
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Srinagarind Hospital, Khon Kaen University
Khon Kaen, , 40002
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Thammasat Hospital
Pathumthani, , 12120
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Adana City Hospital
Adana, , 01170
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Cukurova University Medical Faculty
Adana, , 01250
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Hacettepe University Medical Faculty
Ankara, , 06230
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Ankara Bilkent Sehir Hastanesi
Ankara, , 06800
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Pamukkale University Medical Faculty
Denizli, , 20070
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Eskisehir Osmangazi University Medical Faculty Hospital
Eskisehir, , 26040
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Istanbul University - Cerrahpasa Cardiology Institution
Istanbul, , 34096
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Siyami Ersek Training and Research Hospital
Istanbul, , 34668
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Marmara University Medical Faculty
Istanbul, , 34899
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Ege University Medical Faculty
Izmir, , 35100
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Dokuz Eylul University Medical Faculty
Izmir, , 35340
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Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
Kartal Istanbul, , 34865
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Mersin University Medical Faculty
Mersin, , 33110
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CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'
Cherkasy, , 18009
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CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
Dnipro, , 49059
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SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
Kyiv, , 02000
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State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine
Kyiv, , 03680
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Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'
Lviv, , 79010
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Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
Ternopil, , 46002
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Papworth Hospital NHS Trust
Cambridge, , CB2 0AY
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National Waiting Times Centre Board Golden Jubilee National Hospital
Glasgow, , G81 4DY
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Royal Free Hospital
London, , NW3 2QG
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Hammersmith Hospital
London, , W12 0HS
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Freeman Hospital
Newcastle Upon Tyne, , NE7 7DN
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Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Sheffield, , S10 2RX
