Selexipag (ACT-293987) in Pulmonary Arterial Hypertension (GRIPHON)
Pulmonary Arterial Hypertension
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring pulmonary arterial hypertension, PAH
Eligibility Criteria
Inclusion Criteria:
- Male and female patients 18-75 years old, with symptomatic PAH
- PAH belonging to the following subgroups of the updated Dana Point Clinical Classification Group 1 (Idiopathic, or Heritable, or Drug or toxin induced, or Associated (APAH) with Connective tissue disease, Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, or HIV infection)
- Documented hemodynamic diagnosis of PAH by right heart catheterization, performed at any time prior to Screening
- Six minute walk distance (6MWD) between 50 and 450 m at Screening within 2 weeks prior to the Baseline Visit
- Signed informed consent
Exclusion Criteria:
- Patients with pulmonary hypertension (PH) in the Updated Dana Point Classification Groups 2-5, and PAH Group 1 subgroups that are not covered by the inclusion criteria
- Patients who have received prostacyclin or its analogs within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial
- Patients with moderate or severe obstructive lung disease
- Patients with moderate or severe restrictive lung disease
- Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
- Patients with documented left ventricular dysfunction
- Patients with severe renal insufficiency
- Patients with BMI <18.5 Kg/m2
- Patients who are receiving or have been receiving any investigational drugs within 1 month before the Baseline Visit
- Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6MWT
- Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training
- Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
- Life expectancy less than 12 months
- Females who are lactating or pregnant or plan to become pregnant during the study
- Known hypersensitivity to any of the excipients of the drug formulations
Sites / Locations
- University of South Alabama
- The University of Arizona, Clinical and Translational Science (CATS) Research Center
- University of California San Diego Medical Center (La Jolla)
- Cedars-Sinai Medical Center
- GLVA Healthcare Center
- University of California, Davis, UC Davis Medical Center
- LIU Center for Pulmonary Hypertension
- Lung Health & Sleep Emhancement Center, LLC
- Emory University School of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
- Georgia Health Sciences University
- Georgia Clinical Research
- Clarian North Hospital
- University of Iowa Hospitals & Clinics
- Kentuckiana Pulmonary Associates
- LSU Health Science Center - New Orleans
- Johns Hopkins University School of Medicine
- Tufts Medical Center
- Massachusetts General Hospital - Pulmonary Critical Care Unit
- Massachusetts General Hospital-Pulmonary Critical Care Unit
- Boston University School of Medicine / Boston University Medical Center
- University of Michigan
- Henry Ford Hospital
- Beaumont Hospital
- Washington University School of Medicine
- Newark Beth Isreal Medical Center-Department of Pulmonary Medicine
- Montefiore Medical Center, Weiler Division
- Columbia University Medical Center, Pediatric Cardiology
- Duke University Medical Center
- The Lindner Clinical Trial Center
- University of Cincinnati
- University Hospitals Case Medical Center
- The Ohio State University Medical Center
- Oregon Pulmonary Associates, PC
- Central Bucks Specialists
- Penn Presbyterian Medical Center
- Thomas Jefferson University Hospital
- Vanderbilt Medical Center
- UT Southwestern Medical Center at Dallas
- Baylor College of Medicine
- University of Texas-Houston Health Center Department of Pulmonary & Critical Care
- University of Wisconsin Hospital-Department of Medicine
- St. Luke's Medical Center
- Froedtert Hospital - Medical College of Wisconsin
- Centro de Investigacion y Prevencion Cardiovascular (CIPREC)
- Sanatorio Otamendi y Miroli S.A.
- Hospital Britanico-Pneumology
- Sanatorio San Jose
- Hospital Privado Centro Medico de Cordoba S.A.
- Instituto De Cardiologia de Corrientes
- St. Vincent's Hospital / Heart and Lung Transplant Unit
- Prince Charles Hospital Lung Transplant, Thoracic Department
- Royal Adelaide Hospital, Cardiovascular Investigation Unit (CVIU)
- Flinders Medical Centre, Pulmonary Hypertension, c/- Cardiology
- St Vincent's Hospital
- Royal Hobart Hospital, Centre for Clinical Research
- John Hunter Hospital Autoimmune Resource and Research Centre
- Royal Melbourne Hospital, Department of Respiratory and Sleep Medicine
- Royal Perth Hospital
- Medizinische Universität Graz
- Medical University of Vienna and AKH Cardiology
- The Republican Scientific-Practical Center "Cardiology"
- Minsk City Hospital No. 9
- Minsk Regional Clinical Hospital of the Red Banner of Labour
- Ulb Erasme, Cardiology
- University Hospital Gasthuisberg - Pneumologie
- University of Alberta Hospital - Children's Centre
- Vancouver General Hospital
- Health Sciences Centre
- University of Ottawa Heart Institute
- University Health Network
- Hopital General Juif (Jewish General Hospital)
- Institut Universitaire de Cardiologie et de Pneumologie de Quebec
- Instituto Nacional del Torax Teaching Dept
- Clinica Tabancura- Cardiology Unit
- Pontificia Universidad Catolica de Chile-Departmento De Enfermedades Cardiovasculares
- Peking Union Medical College Hospital, Rheumatology Department
- Cardiovascular Institute & Fuwai Hospital-Pulmonary Vascular Center
- Beijing Shijitan Hospital
- Guangdong General Hospital, Cardiology Department
- Renji Hospital, Rheumatology Department
- Renji Hospital, Cardiology Department
- Shanghai Pulmonary Hospital, Department of Pulmonary Circulation
- Fundacion Cardio Infantil
- Fundacion Clinica Shaio
- Gen Faculty Hosp Prague Cardiology Clin
- Aarhus University Hospital , Cardiology
- Rigshospitalet, Hjertemedicinsk klinik - Cardiology
- Hosp Pradel Lyon - Dpt Pneumology
- Hosp Cote de Nacre - Dpt Pneumology
- Hosp A. Beclere - Dept Pulmo & Resp Intensive Care
- Hosp Huriez - Dpt Internal Medecine
- Hosp Civil - Dpt Pneumology
- Hosp Larrey - Dpt Pneumology
- DRK Kliniken Köpenick
- Universitätsklinikum Carl Gustav Carus, Medizinische Klinik1-Pneumologie/MK1-A13
- "Justus-Liebig-Universität Gießen Zentrum für Innere Medizin Medizinische Klinik II"
- Universität Greifswald / Klinik für Innere Medizin B
- Medizinische Hochschule Hannover / Klinik für Pneumologie
- Thoraxklinik am Universitätsklinikum Heidelberg
- "Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)"
- Praxis für Pneumologie und Allergologie
- Klinik Löwenstein gGmbH, Medizinische Klinik 1, Pneumologie - Kardiologie
- Universitätsklinkum Regensburg / Innere Medizin II
- Onasseio Cardiosurgical Hospital
- "Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály"
- "Semmelweis Egyetem, Pulmonológiai Klinika"
- Egészségügyi Járóbeteg Központ Kardiológiai Intézete - Debrecen
- "Pécsi Tudományegyetem Klinikai Központ,
- "Szegedi Tudományegyetem ÁOK Szent-Györgyi Albert Klinikai Központ, II. sz. Belgyógyászati klinika és Kardiológiai központ"
- Sanjivani Hospitals - Department of Cardiology
- Apollo Hospitals, Chennai
- Frontier Lifeline Hospitals, Dr KM Cherian Heart Foundation, Chennai
- CARE Hospitals Nampally, Cardiology Dep. Hyderabad
- Apollo Indraprastha Hospitals
- Mater Miscordiae University Hospital
- Carmel Medical Center, Pulmonary Unit
- Pulmonology Institute, Hadassah University Hospital at Ein Karem
- Rabin Medical Centre - Pulmonology
- Kaplan Medical - Pulmonary Institute
- The Chaim Sheba Med Ctr -Pulmonology
- Policlinico S. Orsola-Malpighi - Dipartimento Cardio-Toraco-Vascolare
- Seconda Università Degli Studi di Napoli - Azienda Universitaria Policlinico - Dipartimento Assistenziale di medicina Generale, Angiologia, Endocrinologia, Epatogastroenterologia e Reumatologia - Unità Operativa di Reumatologia
- ISMETT - Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione - Dipartimento di Medicina - Divisione di Pneumologia
- Gil Medical Centre
- Seoul Nathional University Hospital
- Yonsei University Health System Dept of Cardiology
- Samsung Medical Center, Division of Cardiology
- "The Catholic University of Korea, Seoul St. Mary's Hospital Department of Cardiology"
- Institut Jantung Negara (National Heart Institute)
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubrian
- Instituto Nacional de Cardiologia (INC) Ignacio Chavez
- VU Medisch Centrum / Afdeling longziekten, secretariaat 4A 48
- Academisch Ziekenhuis Maastricht / Department of Pulmonary Diseases
- St. Antonius Ziekenhuis afdeling Longziekten
- Erasmus Medisch Centrum Rotterdam afdeling longziekten
- Hospital Nacional Edgardo Rebagliati / Unidad de Investigacion Cardiologia 2
- Instituto de Enfermedades Respiratorias Clinica San Gabriel
- "Uniwersyteckie Centrum Kliniczne II Klinika Kardiologii i Elektroterapii Serca"
- "Instytut Kardiologii Collegium Medium UJ Krakowski Szpital Specjalistyczny im Jana Pawła II Klinika Chorób Serca i Naczyń"
- "Instytut Gruźlicy i Chorób Płuc Klinika Chorób Wewnętrznych Klatki Piersiowej"
- "Wojewódzki Specjalistyczny Szpital im. dr Władysława Biegańskiego Oddział Kardiologiczny, II Katedra i Klinika Kardiologii UM"
- "Institutul de Pneumologie "Marius Nasta", I. Clinica de Pneumoftiziologie"
- "Spitalul Clinic de Pneumoftiziologie Iasi Sectia Clinica I de Pneumoftiziologie"
- Municipal Medical Institution City Hospital #5
- Regional Clinical Hospital # 1
- Kemerovo Cardiology Dispensary / Kemerovo Regional Hospital
- Scientific Research Institute of Pulmonology of the Federal Medical and Biological Agency of Russia
- State Institution, "Institute fo Rheumatology of RAMS"
- The Institution of the Clinical Cardiology named after A. L. Myaskinov
- Limited liability company, Consultative diagnostic centre Healthy Joints
- V. A. Almazov Institute of Cardiology, Russian Ministry of Healthcare and Social Development / Medical Treatment and Rehabilitation Complex
- Cardiology Scientific Research Institute of Tomsk Scientific Center of RAMs, Siberian Branch / Cardiovascular Surgery Department
- Tomsk Regional Clinical Hospital/ Pulmonology Unit
- "Klinički Centar Srbije, Klinika za pulmologiju"
- "Kliničko-bolnički centar Zemun, Kardiološko odeljenje"
- National Heart Centre (NHC) Singapore
- Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH a.s.
- Hosp Vall D'Hebron - Barcelona - Pneumology
- Clinic-Barcelona
- Hospital 12 Octubre
- Sahlgrenska Universitetssjukhuset, Kardiologi
- Linköping University Hospital, Cardiology
- Umeå University Hospital, Cardiology (Umeå)
- Uppsala Akademiska Sjukhuset, Kardiologkliniken 50F
- University Hospital Basel Division of Pneumology
- Universitätsspital Bern, Clinic for Pneumology (Inselspital)
- HUG Hôpitaux Universitaires de Genève; Pneumology, PAH
- Kantonsspital St. Gallen Klinik für Pneumologie
- Kaohsiung Veterans General Hospital (KVGH)
- National Taiwan University Hospital / Department of Surgery
- Srinagarind Hospital, Khon Kaen University, Division of Allergy-Immunology and Rheumatology, Department of Medicine
- Çukurova Üniversitesi Tıp Fakültesi Kardiyoloji Anabilim Dalı
- Istanbul Üniversitesi Kardiyoloji Enstitisü
- Marmara Üniversitesi Tip Fakultesi Kardiyoloji Anabilim Dali
- Dokuz Eylül Üniversitesi Tıp Fakültesi Kardiyoloji Anabilim Dalı
- "Dnipropetrovsk State Medical Academy, Municipal Institution ""Dnipropetrovsk Regional Clinic Diagnostic Center""
- Health Care Municipal Institution, City Clinical Hospital #13
- Public Institution "F.H. Yanovski Phthisiology and Pulmonology National Institute Under Ukrainian Academy of Medical Sciences"
- Lviv Regional Clinical Hospital
- Golden Jubilee - Pulm Vascular Unit
- Royal Free & Ucms Rheumatology Unit
- Hammersmith
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
1
2
Selexipag is up-titrated from Day 1 to Week 12 to each patient's maximum tolerated dose in the range of 200-1600 µg twice a day (b.i.d.) in 200 µg steps starting with one 200 µg oral tablet on Day 1. From Day 2 onwards, a b.i.d. dose regimen with an interval of approximately 12 hours is followed. If this dose (selexipag 200 μg b.i.d.) is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg. Up-titration is followed by a stable maintenance treatment period from Week 12 onwards, up to Week 26, at the maximum tolerated dose
Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed