Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— SERAPHIN OL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00667823
• Other study ID #: AC-055-303
• Status: Completed
• Phase: Phase 3
• Start date: October 17, 2008
• Est. completion date: December 7, 2020

Study information

• Verified date: January 2022
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 550
• Est. completion date: December 7, 2020
• Est. primary completion date: December 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Macitentan
Tablet, oral administration, 10 mg dose once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Finland,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Malaysia,  Mexico,  Netherlands,  Peru,  Poland,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Sweden,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)