Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension
SERAPHIN OL
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
1 other identifier
interventional
550
33 countries
152
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2008
Longer than P75 for phase_3
152 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2008
CompletedFirst Posted
Study publicly available on registry
April 28, 2008
CompletedStudy Start
First participant enrolled
October 17, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 7, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 7, 2020
CompletedResults Posted
Study results publicly available
February 10, 2022
CompletedMarch 30, 2025
March 1, 2025
12.1 years
April 24, 2008
December 2, 2021
March 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) up to 28 Days After Study Treatment Discontinuation
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.
Up to 28 days after study treatment discontinuation (Up to 12 years)
Number of Participants With Death up to 28 Days After Study Treatment Discontinuation
Number of participants with deaths up to 28 days after study treatment discontinuation were reported.
Up to 28 days after study treatment discontinuation (Up to 12 years)
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) up to 28 Days After Study Treatment Discontinuation
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE are defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically significant, or requires intervention to prevent at least one of the outcomes listed above.
Up to 28 days after study treatment discontinuation (Up to 12 years)
Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment
Number of participants with AEs leading to permanent discontinuation of study treatment were reported. An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Up to 28 days after study treatment discontinuation (Up to12 years)
Number of Participants With Treatment Emergent Abnormal Liver Tests up to 28 Days After Study Treatment Discontinuation
Number of participants with treatment-emergent abnormal liver tests: Alanine aminotransferase (ALT) greater than (\>) 3\*upper limit of normal (ULN) or aspartate aminotransferase (AST) \>3\* ULN, ALT \>5\* ULN or AST \>5\*ULN, ALT \>8\*ULN or AST \>8\*ULN, total bilirubin (TBIL) \>2\*ULN, ALT \>3\*ULN or AST \>3\*ULN and TBIL \>2\*ULN at any time were reported.
Up to 28 days after study treatment discontinuation (Up to12 years)
Number of Participants With Treatment Emergent Hemoglobin Abnormality up to 28 Days After Study Treatment Discontinuation
Number of participants with treatment-emergent hemoglobin (HGB) abnormality up to 28 days after study treatment discontinuation were reported. Participants assessed for different categories of HGB were \<=80 grams/Liter (g/L), \<=100g/L, decrease from baseline \>=20 g/L, and decrease from baseline \>=50 g/L.
Up to 28 days after treatment discontinuation (Up to 12 years)
Study Arms (1)
ACT-064992
EXPERIMENTALACT-064992
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Actelionlead
Study Sites (158)
University of Alabama at Birmingham
Birmingham, Alabama, 35249-0001, United States
Arizona Pulmonary Specialists
Phoenix, Arizona, 85012, United States
University of California, San Diego
La Jolla, California, 92037, United States
GLVA Healthcare Center
Los Angeles, California, 90073, United States
Santa Barbara Cottage Hospital
Santa Barbara, California, 93105, United States
Liu Center for Pulmonary Hypertension
Torrance, California, 90502-2006, United States
University of Colorado CARDIAC AND VASCULAR CENTER
Aurora, Colorado, 80045-2548, United States
University of Florida - Division of Pulmonology
Gainesville, Florida, 32610, United States
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32259, United States
Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
Atlanta, Georgia, 30322, United States
Pulmonary & Critical Care of Atlanta
Atlanta, Georgia, 30342-1713, United States
Atlanta Institute for Medical Research
Decatur, Georgia, 30030, United States
University of Chicago
Chicago, Illinois, 60637-1432, United States
University of Iowa, Pulmonary Hypertension Program
Iowa City, Iowa, 52242-1081, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Kentuckiana Pulmonary Associate, PLLC
Louisville, Kentucky, 40202, United States
Louisiana State University Health Sciences Center
New Orleans, Louisiana, 70112-1393, United States
Maine Medical Center
Portland, Maine, 04102-3134, United States
University of Maryland School of Medicine; Division of Cardiology
Baltimore, Maryland, 21201-1544, United States
Pulmonary/Critical Care Division/Tufts New England Medical Center
Boston, Massachusetts, 02111-1552, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Boston University School of Medicine
Boston, Massachusetts, 02118, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Harper Univ. Hospital/ Wayne State University
Detroit, Michigan, 48201, United States
Washington University School of Medicine
St Louis, Missouri, 63110-1010, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
University of NJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08903-0010, United States
Columbia University Medical Center - Pediatric Cardiology
New York, New York, 10032, United States
Duke University Medical Center
Durham, North Carolina, 27710-0001, United States
University of Cincinnati Ohio Heart Health Center
Cincinnati, Ohio, 45219-2906, United States
Ohio State University, Div. of Pul. & Critical Care
Columbus, Ohio, 43210, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Texas Medical Center - St. Paul University
Dallas, Texas, 75390-8550, United States
Baylor College of Medicine and the Methodist Hospital,
Houston, Texas, 77030, United States
University of Texas Houston Health Center
Houston, Texas, 77030, United States
Intermountain Med Ctr- Pulm Dept Heart and Lung Ctr
Murray, Utah, 84157-5701, United States
Sentara Hospitals T/A Sentara Cardiovascular Research Intitute
Norfolk, Virginia, 23507-1904, United States
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53125, United States
Sanatorio Otamendi y Miroli S.A.
Buenos Aires, Ciudad Autonoma, C1121ABL, Argentina
Hospital Britanico
Buenos Aires, Ciudad Autonoma, C1280AEB, Argentina
Sanatorio MITRE
Buenos Aires, C1039AAO, Argentina
Fundacion Favaloro
Buenos Aires, C1093AAS, Argentina
Instituto Cardiologia Corrientes
Corrientes, W3400AMZ, Argentina
Htal Italiano Cordoba
Córdoba, X5004BAL, Argentina
Htla privado de Cordoba
Córdoba, x5016keh, Argentina
Hospital Italiano - Garibaldi de Rosario
Santa Fe, S2001ODA, Argentina
St. Vincent's Hospital
Darlinghurst, 2010, Australia
The Alfred Hospital
Melbourne, 3004, Australia
Royal Brisbane Hospital
Sunshine Coast, 4558, Australia
Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
Vienna, 1090, Austria
Republican reserach - Pratical Centre of Cardiology
Minsk, 220036, Belarus
Minsk Regional Clinical Hospital
Minsk, 223041, Belarus
Vitebsk Regional Clinical Hospital
Vitebsk, 210037, Belarus
University Hospital Gasthuisberg
Leuven, 3000, Belgium
Mhat Nat Card Hosp - Pediatric Clinic
Sofia, BG, 1309, Bulgaria
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4, Canada
London Health Sciences Centre
London, Ontario, N6C 2R5, Canada
Toronto General Hospital
Toronto, Ontario, M5G 2N2, Canada
L'Hopital Laval
Sainte-Foy, Quebec, G1V 4G5, Canada
Hospital del Torax
Santiago, 7500691, Chile
Pontificia Universidad Catolica de Chile
Santiago, 833034, Chile
Hospital San Juan de Dios
Santiago, 8350488, Chile
Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
Beijing, 100029, China
Peking Union Medical College Hospital, Rheumatology Department
Beijing, 100032, China
Guangdong General Hospital, Cardiology Department
Guangzhou, 510080, China
Jiangsu Province Hospital - Pneumology Department
Nanjing, 210029, China
Renji Hospital, Rheumatology Department
Shanghai, 200001, China
Zhongshan Hospital Fudan University, Cardiology Department
Shanghai, 200032, China
Renji Hospital, Cardiology Department
Shanghai, 200127, China
Shanghai Pulmonary Hospital Department of Pulmonary Circulation
Shanghai, 200433, China
Fundacion Cardiovascular de Colombia
Floridablanca, Santander Department, Colombia
Fundacion Clinica Shaio
Bogotá, Colombia
Clinical Hospital Center
Rijeka, 51 000, Croatia
Helsinki University Central Hospital
Helsinki, 00290, Finland
Hosp Bicetre - Dept Pulmo & Resp Intensive Care
Le Kremlin-Bicêtre, 94275, France
Hopital Arnaud de Villeneuve Service des Maladies Respiratoires
Montpellier, 34295, France
Hopital Haut-Leveque-Maison du Haut-Leveque
Pessac, 33604, France
Unfallkrankenhaus Berlin, Klinik für Innere Medizin
Berlin, 12683, Germany
Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
Cologne, 50924, Germany
Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
Dresden, 01307, Germany
Universitätsklinikum Essen, Klinik für Kardiologie , Zentrum für Innere Medizin
Essen, 45122, Germany
Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med. / Pneumologie
Giessen, 35392, Germany
Universität Greifswald / Klinik für Innere Medizin B,
Greifswald, 17475, Germany
Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
Hamburg, 20246, Germany
Medizinische Hochschule Hannover / Klinik für Pneumologie
Hanover, 30625, Germany
Thoraxklinik am Universitätsklinikum Heidelberg
Heidelberg, 69126, Germany
Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
Homburg/Saar, 66421, Germany
Universtätsklinik Leipzig
Leipzig, 04103, Germany
Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
Munich, 81377, Germany
Universitatsklinikum Regensburg/Innere Medizin II
Regensburg, 93053, Germany
Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
Hong Kong, Hong Kong
Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
Budapest, 1096, Hungary
"Semmelweis Egyetem, Pulmonológiai Klinika"
Budapest, 1125, Hungary
University of Pecs, Medical School/Heart Institute and 1st Department of Internal Medicine
Pécs, 7624, Hungary
University of Szeged Albert Szent-Gyorgyi Medical & Pharmaceutical Center
Szeged, 6720, Hungary
Life Care Institute of Medical Science & Research, Ahmedabad
Ahmedabad, 382428, India
Care Hospital
Hyderabad, 500001, India
Seth GS Medical College & King Edward VII Memorial (KEM) Hospital / Department Of Cardiology
Mumbai, 400012, India
P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
Mumbai, 400016, India
G B Pant Hospital & Maulana Azad Medical College
New Delhi, 110 002, India
Deenanath Mangeshkar Hospital and Research Centre
Pune, 411 004, India
Rambam Health Care Campus / Division of Medicine, Institute of Pulmonology
Haifa, 31096, Israel
Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
Haifa, 34362, Israel
Rabin Medical Center - Belinson campus - Pulmonary Institute
Petach - Tikvah, 49100, Israel
Pulmonary Institute, Kaplan Medical Center
Rehovot, 76100, Israel
Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
Tel Aviv, 64239, Israel
The pulmonary institute Sheba Medical centre
Tel Litwinsky, 52621, Israel
IRCCS Policlinico San Matteo Policlinico / Dipartimento di Cardiologia
Pavia, 207100, Italy
Policlinico Umberto I, Cardiologia
Roma, 00161, Italy
Institut Jantung Negara (National Heart Institute)
Kuala Lumpur, 50400, Malaysia
Instituto Nacional de Cardiología (INC) Ignacio Chávez
Mexico City, 14080, Mexico
Unidad de Investigación Clinica en Medicina
Monterrey, 64718, Mexico
VU Medisch Centrum, Dept. Pulmonology 4A 48
Amsterdam, 1081 HV, Netherlands
St. Antonius ziekenhuis
Nieuwegein, 3435 CM, Netherlands
Hospital Alberto Sabogal Sologuren - EsSALUD
Callao, Callao 02, Peru
Clinica Medica Cayetano Heredia
Lima, 31, Peru
Instituto de Enfermedades Respiratorias
Lima, 32, Peru
Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
Krakow, 31-202, Poland
Cardiology Otwock Priv
Otwock, 05-400, Poland
III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
Zabrze, 41-800, Poland
Institutul de boli cardiovasculare / Clinica de Cardiologie
Bucharest, 022328, Romania
Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
Bucharest, 050159, Romania
Municipal Health Care Institution Kemerovo Cardiology Dispensary
Kemerovo, 650002, Russia
Federal State Institution "State Scientific Research Centre of Preventive Medicine" of Rosmedtechnology
Moscow, 101990, Russia
Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
Moscow, 105077, Russia
State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
Moscow, 117049, Russia
Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
Moscow, 121552, Russia
State Educational Institution "St Petersburg Medical Academy of Postgraduate Education" of Federal Agency of Public Health and Social Development
Saint Petersburg, 193015, Russia
State Educational Institution of High Professional Education "St Petersburg State Medical
Saint Petersburg, 197 022, Russia
Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
Saint Petersburg, 197341, Russia
State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
Tomsk, 634012, Russia
Tomsk Regional Clinical Hospital / Pulmonology Unit
Tomsk, 634063, Russia
Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
Yaroslavl, 150 003, Russia
Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
Yekaterinburg, 620102, Russia
University Children's Hospital (UNIVERZITETSKA DECJA KLINKIKA)
Belgrade, 11000, Serbia
University Clinical Center of Serbia/ Institute for Lung Diseases and Tuberculosis
Belgrade, 11000, Serbia
Zemun Clinical Hospital (Klinicko-bolnicki centar Zemun) / Department of Cardiology
Belgrade, 11080, Serbia
National University Hospital/ The Heart Institute
Singapore, 119228, Singapore
National Heart Centre (Nhc) Singapore
Singapore, 169609, Singapore
National Institute of Cardiovascular Diseases (Slovenska zdravotnicka univerzita) / Faculty of Medical Specialty Studies (Fakulta zdravotnickych speci
Bratislava, 833 48, Slovakia
Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií)
Bratislava, 833 48, Slovakia
Tread Research
Cape Town, 7505, South Africa
Chris Hani Baragwanath Hospital, Department of Cardiology
Johannesburg, 2013, South Africa
Netcare Milpark Hospital,Center for Chest Disease
Johannesburg, 2193, South Africa
Block 4, Vergelegen Medi-Clinic
Somerset West, 7130, South Africa
University Hospital of Lund, Dept. of Cardiology
Lund, 221 85, Sweden
Uppsala University Hospital, Cardiology
Uppsala, 751 85, Sweden
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
Taipei, 100, Taiwan
Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
Bangkok, 10400, Thailand
Siriraj Hospital, Mahidol University
Bangkok, 10700, Thailand
Maharaj Nakorn Chiang Mai Hospital, Division of Rheumatology
Chiang Mai, 50200, Thailand
Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
Khon Kaen, 40002, Thailand
Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
Dnipro, 49060, Ukraine
Danylo Galytskyi Lviv State Medical University
Lviv, 79010, Ukraine
Odessa State Medical University, Military-medical Clinical Center of the South region
Odesa, 65044, Ukraine
Royal Free Hospital
London, NW3 2QG, United Kingdom
Related Publications (2)
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.
PMID: 35819570DERIVEDKrause 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.
PMID: 29501590DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The limitation of the open-label study design was the open label nature of the trial due to which the number of participants decreased over time to the extent that 10 percent (%) and 2.4% of participants (N=550) remained in the study at Years 7 and 9, respectively.
Results Point of Contact
- Title
- Senior Clinical Leader PH
- Organization
- Actelion Pharmaceuticals Ltd
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2008
First Posted
April 28, 2008
Study Start
October 17, 2008
Primary Completion
December 7, 2020
Study Completion
December 7, 2020
Last Updated
March 30, 2025
Results First Posted
February 10, 2022
Record last verified: 2025-03