Clinical trial NCT00667823: Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension
Official title: Long-term Single-arm Open-label Extension Study of the SERAPHIN Study, to Assess the Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: SERAPHIN
Pulmonary Arterial Hypertension
ACT-064992
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2008-04-28
Enrollment: 550
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of the AC 055 303/SERAPHIN OL study, which will follow the AC 055 302/SERAPHIN study, will be to assess the long-term safety and tolerability of ACT 064992 in patients with symptomatic PAH.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to initiation of any study-mandated procedure.
* Patients with pulmonary arterial hypertension and having completed the event-driven study, AC 055 302/SERAPHIN, or Patients who have experienced a clinical worsening of PAH in AC 055 302/SERAPHIN and for whom a written approval to roll over into this study has been obtained from the Sponsor.
* Women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception during study treatment and for at least 28 days after study treatment termination.

Exclusion Criteria:

* Any major violation of protocol AC 055 302/SERAPHIN.
* Pregnancy or breast-feeding.
* AST and/or ALT \> 3 times the upper limit of the normal range.
* Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
* Known hypersensitivity to ACT 064992 or any of the excipients.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) up to 28 Days After Study Treatment Discontinuation
timeFrame: Up to 28 days after study treatment discontinuation (Up to 12 years)
measure: Number of Participants With Death up to 28 Days After Study Treatment Discontinuation
timeFrame: Up to 28 days after study treatment discontinuation (Up to 12 years)
measure: Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) up to 28 Days After Study Treatment Discontinuation
timeFrame: Up to 28 days after study treatment discontinuation (Up to 12 years)
measure: Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment
timeFrame: Up to 28 days after study treatment discontinuation (Up to12 years)
measure: Number of Participants With Treatment Emergent Abnormal Liver Tests up to 28 Days After Study Treatment Discontinuation
timeFrame: Up to 28 days after study treatment discontinuation (Up to12 years)
measure: Number of Participants With Treatment Emergent Hemoglobin Abnormality up to 28 Days After Study Treatment Discontinuation
timeFrame: Up to 28 days after treatment discontinuation (Up to 12 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: GLVA Healthcare Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Torrance
country: United States
facility: Liu Center for Pulmonary Hypertension
state: California
city: Aurora
country: United States
facility: University of Colorado CARDIAC AND VASCULAR CENTER
state: Colorado
city: Gainesville
country: United States
facility: University of Florida - Division of Pulmonology
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
state: Georgia
city: Atlanta
country: United States
facility: Pulmonary & Critical Care of Atlanta
state: Georgia
city: Decatur
country: United States
facility: Atlanta Institute for Medical Research
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa, Pulmonary Hypertension Program
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associate, PLLC
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland School of Medicine; Division of Cardiology
state: Maryland
city: Boston
country: United States
facility: Pulmonary/Critical Care Division/Tufts New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Harper Univ. Hospital/ Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New Brunswick
country: United States
facility: University of NJ - Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center - Pediatric Cardiology
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Ohio Heart Health Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Div. of Pul. & Critical Care
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Medical Center - St. Paul University
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine and the Methodist Hospital,
state: Texas
city: Houston
country: United States
facility: University of Texas Houston Health Center
state: Texas
city: Murray
country: United States
facility: Intermountain Med Ctr- Pulm Dept Heart and Lung Ctr
state: Utah
city: Norfolk
country: United States
facility: Sentara Hospitals T/A Sentara Cardiovascular Research Intitute
state: Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Sanatorio Otamendi y Miroli S.A.
state: Ciudad Autonoma
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
state: Ciudad Autonoma
city: Buenos Aires
country: Argentina
facility: Sanatorio MITRE
city: Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: Cordoba
country: Argentina
facility: Htal Italiano Cordoba
city: Cordoba
country: Argentina
facility: Htla privado de Cordoba
city: Corrientes
country: Argentina
facility: Instituto Cardiologia Corrientes
city: Santa Fe
country: Argentina
facility: Hospital Italiano - Garibaldi de Rosario
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Sunshine Coast
country: Australia
facility: Royal Brisbane Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
city: Minsk
country: Belarus
facility: Republican reserach - Pratical Centre of Cardiology
city: Minsk
country: Belarus
facility: Minsk Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Sofia
country: Bulgaria
facility: Mhat Nat Card Hosp - Pediatric Clinic
state: BG
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Sainte-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Santiago de Chile
country: Chile
facility: Hospital del Torax
city: Santiago de Chile
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Santiago
country: Chile
facility: Hospital San Juan de Dios
city: Beijing
country: China
facility: Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Rheumatology Department
city: Guangzhou
country: China
facility: Guangdong General Hospital, Cardiology Department
city: Nanjing
country: China
facility: Jiangsu Province Hospital - Pneumology Department
city: Shanghai
country: China
facility: Renji Hospital, Rheumatology Department
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University, Cardiology Department
city: Shanghai
country: China
facility: Renji Hospital, Cardiology Department
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital Department of Pulmonary Circulation
city: Floridablanca
country: Colombia
facility: Fundacion Cardiovascular de Colombia
state: Santander
city: Bogota
country: Colombia
facility: Fundacion Clinica Shaio
city: Rijeka
country: Croatia
facility: Clinical Hospital Center
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Le Kremlin-Bicêtre cedex
country: France
facility: Hosp Bicetre - Dept Pulmo & Resp Intensive Care
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve Service des Maladies Respiratoires
city: Pessac
country: France
facility: Hopital Haut-Leveque-Maison du Haut-Leveque
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin, Klinik für Innere Medizin
city: Dresden
country: Germany
facility: Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Kardiologie , Zentrum für Innere Medizin
city: Giessen
country: Germany
facility: Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med. / Pneumologie
city: Greifswald
country: Germany
facility: Universität Greifswald / Klinik für Innere Medizin B,
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover / Klinik für Pneumologie
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
city: Homburg/Saar
country: Germany
facility: Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
city: Koln
country: Germany
facility: Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
city: Leipzig
country: Germany
facility: Universtätsklinik Leipzig
city: Munich
country: Germany
facility: Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
city: Regensburg
country: Germany
facility: Universitatsklinikum Regensburg/Innere Medizin II
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
city: Budapest
country: Hungary
facility: "Semmelweis Egyetem, Pulmonológiai Klinika"
city: Pecs
country: Hungary
facility: University of Pecs, Medical School/Heart Institute and 1st Department of Internal Medicine
city: Szeged
country: Hungary
facility: University of Szeged Albert Szent-Gyorgyi Medical & Pharmaceutical Center
city: Ahmedabad
country: India
facility: Life Care Institute of Medical Science & Research, Ahmedabad
city: Hyderabad
country: India
facility: Care Hospital
city: Mumbai
country: India
facility: Seth GS Medical College & King Edward VII Memorial (KEM) Hospital / Department Of Cardiology
city: Mumbai
country: India
facility: P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
city: New Delhi
country: India
facility: G B Pant Hospital & Maulana Azad Medical College
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre
city: Haifa
country: Israel
facility: Rambam Health Care Campus / Division of Medicine, Institute of Pulmonology
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
city: Petach - Tikvah
country: Israel
facility: Rabin Medical Center - Belinson campus - Pulmonary Institute
city: Rehovot
country: Israel
facility: Pulmonary Institute, Kaplan Medical Center
city: Tel Hashomer
country: Israel
facility: The pulmonary institute Sheba Medical centre
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo Policlinico / Dipartimento di Cardiologia
city: Roma
country: Italy
facility: Policlinico Umberto I, Cardiologia
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara (National Heart Institute)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiología (INC) Ignacio Chávez
city: Monterrey
country: Mexico
facility: Unidad de Investigación Clinica en Medicina
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum, Dept. Pulmonology 4A 48
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis
city: Callao
country: Peru
facility: Hospital Alberto Sabogal Sologuren - EsSALUD
city: Lima
country: Peru
facility: Clinica Medica Cayetano Heredia
city: Lima
country: Peru
facility: Instituto de Enfermedades Respiratorias
city: Krakow
country: Poland
facility: Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
city: Otwock
country: Poland
facility: Cardiology Otwock Priv
city: Zabrze
country: Poland
facility: III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
city: Bucharest
country: Romania
facility: Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
city: Bucuresti
country: Romania
facility: Institutul de boli cardiovasculare / Clinica de Cardiologie
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
city: Kemerovo
country: Russian Federation
facility: Municipal Health Care Institution Kemerovo Cardiology Dispensary
city: Moscow
country: Russian Federation
facility: Federal State Institution "State Scientific Research Centre of Preventive Medicine" of Rosmedtechnology
city: Moscow
country: Russian Federation
facility: Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
city: Moscow
country: Russian Federation
facility: State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
city: Moscow
country: Russian Federation
facility: Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
city: St Petersburg
country: Russian Federation
facility: State Educational Institution "St Petersburg Medical Academy of Postgraduate Education" of Federal Agency of Public Health and Social Development
city: St Petersburg
country: Russian Federation
facility: State Educational Institution of High Professional Education "St Petersburg State Medical
city: St. Petersburg
country: Russian Federation
facility: Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
city: Tomsk
country: Russian Federation
facility: State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital / Pulmonology Unit
city: Yaroslavl
country: Russian Federation
facility: Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
city: Belgrade
country: Serbia
facility: University Children's Hospital (UNIVERZITETSKA DECJA KLINKIKA)
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia/ Institute for Lung Diseases and Tuberculosis
city: Belgrade
country: Serbia
facility: Zemun Clinical Hospital (Klinicko-bolnicki centar Zemun) / Department of Cardiology
city: Singapore
country: Singapore
facility: National University Hospital/ The Heart Institute
city: Singapore
country: Singapore
facility: National Heart Centre (Nhc) Singapore
city: Bratislava
country: Slovakia
facility: National Institute of Cardiovascular Diseases (Slovenska zdravotnicka univerzita) / Faculty of Medical Specialty Studies (Fakulta zdravotnickych speci
city: Bratislava
country: Slovakia
facility: Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií)
city: Cape Town
country: South Africa
facility: Tread Research
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital, Department of Cardiology
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital,Center for Chest Disease
city: Somerset West
country: South Africa
facility: Block 4, Vergelegen Medi-Clinic
city: Lund
country: Sweden
facility: University Hospital of Lund, Dept. of Cardiology
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Cardiology
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital, Division of Rheumatology
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
city: Dnepropetrovsk
country: Ukraine
facility: Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
city: Lviv
country: Ukraine
facility: Danylo Galytskyi Lviv State Medical University
city: Odessa
country: Ukraine
facility: Odessa State Medical University, Military-medical Clinical Center of the South region
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References:
citation: Souza R, Delcroix M, Galie N, Jansa P, Mehta S, Pulido T, Rubin L, Sastry BKS, Simonneau G, Sitbon O, Torbicki A, Boyanova N, Chamitava L, Stein C, Channick RN. Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension. Adv Ther. 2022 Sep;39(9):4374-4390. doi: 10.1007/s12325-022-02199-x. Epub 2022 Jul 12.
citation: Krause A, Zisowsky J, Dingemanse J. Modeling of pharmacokinetics, efficacy, and hemodynamic effects of macitentan in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2018 Apr;49:140-146. doi: 10.1016/j.pupt.2018.02.005. Epub 2018 Feb 28.