Uno studio su Selexipag come trattamento aggiuntivo allo standard di cura nei bambini con ipertensione arteriosa polmonare (SALTO)
Uno studio randomizzato, multicentrico, in doppio cieco, controllato con placebo, a gruppi paralleli, guidato dagli eventi, sequenziale di gruppo con periodo di estensione in aperto per valutare l'efficacia e la sicurezza di Selexipag come trattamento aggiuntivo allo standard di cura nei bambini Età >=2 a
The purpose of this study is to evaluate whether the addition of selexipag to standard of care treatment delays disease progression in children with Pulmonary Arterial Hypertension (PAH) in comparison to placebo.
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
Pediatric PAH is a rare and progressive disorder associated with considerable morbidity and mortality. Given the significant medical need to develop treatments in children with PAH, further clinical studies in the pediatric population are therefore needed to provide more data for the management of PAH in children. Selexipag (JNJ-67896049) is an orally available, selective, and long-acting non-prostanoid agonist of the prostacyclin receptor approved and commercially available for the treatment of adult participants with PAH. Selexipag and its metabolite possess anti-fibrotic, anti-proliferative, and anti-thrombotic properties. Currently, no medicines targeting prostacyclin pathway are approved for pediatric use in PAH. An effective and orally available therapy acting on the prostacyclin receptor such as selexipag introduced at medically appropriate stage of PAH disease, and primarily in combination with current first-line oral PAH-specific medicines in participants in need of additional therapy because of insufficient disease control would represents a major advance to the therapeutic management of PAH pediatric participants. This study consists of a screening period of up to 6 weeks and a double-blind treatment period, including up-titration and maintenance periods, followed by a 3-year open-label extension period (OLEP) and a 30-day safety follow-up period that occurs after the last dose of study intervention (either double-blind or open-label). Safety, pharmacokinetic and efficacy assessments will be performed during the study. An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an ongoing basis, to review interim data, and to ensure the continuing safety of the participants enrolled in this study. The approximate duration of the study is 8 years.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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South Brisbane, Australia, 4101
- Queensland CHILDREN'S HOSPITAL
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Brussels, Belgio, 1070
- ULB Hôpital Erasme
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Ghent, Belgio, 9000
- Universitair Ziekenhuis Gent
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Leuven, Belgio, 3000
- Universitaire Ziekenhuizen Leuven
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Minsk, Bielorussia, 220013
- State Institution Republican Scientific And Practical Center For Pediatric Surgery
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Minsk, Bielorussia, 220118
- Health Institution 4Th City Children'S Clinical Hospital
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Blumenau, Brasile, 89030-101
- Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao
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Brasília, Brasile, 70310-500
- Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF
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Curitiba, Brasile, 80250-060
- Hospital Pequeno Principe
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Fortaleza, Brasile, 60840-285
- Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
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Porto Alegre, Brasile, 90020-090
- Irmandade Santa Casa de Misericordia de Porto Alegre
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Porto Alegre, Brasile, 90620-001
- Fundacao Universitaria de Cardiologia
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São Paulo, Brasile, 01221-020
- Irmandade Santa Casa de Misericordia de Sao Paulo
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São Paulo, Brasile, 04024 002
- SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
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Sofia, Bulgaria, 1309
- Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
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Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- Stollery Children's Hospital
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital For Sick Children
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Beijing, Cina, 100029
- Beijing Anzhen Hospital
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Guangzhou, Cina, 510623
- Guangzhou Women And Childrens Medical Center
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Qingdao, Cina, 266000
- Qingdao Women and Children's Hospital
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Qingdao, Cina, 266000
- Qingdao Women and Children's Hospital 1
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Shanghai, Cina, 200127
- Shanghai Childrens Medical Center
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Shanghai, Cina, 201102
- Children S Hospital of Fudan University
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Shenyang, Cina, 110000
- The General Hospital of Northern Theater Command
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Bogotá, Colombia, 0000000
- Clinica San Rafael
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Bogotá, Colombia, 0000000
- Fundacion Neumologica Colombiana
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Bogotá, Colombia
- Fundacion Santa Fe de Bogota
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Cali, Colombia, 760042
- Clínica Imbanaco S.A.S.
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Piedecuesta, Colombia, 681017
- Fundacion Cardiovascular de Colombia
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Soledad, Colombia, 0000000
- Hospital Universidad del Norte
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Seoul, Corea del Sud, 03080
- Seoul National University Hospital
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Seoul, Corea del Sud, 06351
- Samsung Medical Center
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Seoul, Corea del Sud, 120-752
- Severance Hospital Yonsei University Health System
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Yangsan, Corea del Sud, 50612
- Pusan National University Yangsan Hospital
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Helsinki, Finlandia, 29
- New Children's Hospital of the Helsinki University Hospital (HUS)
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Lille, Francia, 59037
- Hôpital Cardiologique - Chru Lille
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Marseille, Francia, 13385
- Hopital de la Timone
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Montpellier, Francia, 34295
- CHU Arnaud de Villeneuve
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Paris, Francia, 75015
- Hôpital Necker - Enfants Malades
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Pessac, Francia, 33604
- Hôpital Cardiologique Du Haut-Lévêque
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Toulouse, Francia, 31059
- Chu Hopital Des Enfants
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Freiburg im Breisgau, Germania, 70106
- Universitätsklinikum Freiburg Zentrum
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Heidelberg, Germania, D-69120
- Universitaetsklinikum Heidelberg
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Leipzig, Germania, 04289
- Herzzentrum Leipzig GmbH
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München, Germania, 81377
- Klinikum der Universitaet Muenchen
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Dublin, Irlanda
- Our Lady's Children's Hospital
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Haifa, Israele, 3109601
- Rambam Medical Center
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Ramat Gan, Israele, 52621
- Sheba Medical Center
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Bologna, Italia, 40138
- Azienda Ospedaliera Policlinico S. Orsola-Malpighi
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Milan, Italia, 20162
- ASST Grande Ospedale Metropolitano Niguarda
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Padova, Italia
- Universta Degli Studi Di Padova
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Roma, Italia, 00193
- Ospedale Pediatrico Bambin Gesù
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S. Donato Milanese, Italia, 20097
- IRCCS Policlinico San Donato
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Torino, Italia, 10126
- AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
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Vilnius, Lituania, LT08661
- Vilnius University Hospital Santariskiu Clinics
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Kuala Lumpur, Malaysia, 50400
- National Heart Institute
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Guadalajara, Messico, 44160
- CICUM San Miguel
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Monterrey, Messico, 64718
- Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
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México, Messico, 52787
- Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
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Gdansk, Polonia, 80 952
- Uniwersyteckie Centrum Kliniczne
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Krakow, Polonia, 30-663
- Uniwersytecki Szpital Dzieciecy w Krakowie
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Poznan, Polonia, 60 572
- Szpital Kliniczny im Karola Jonschera
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Warsaw, Polonia, 04-730
- Instytut Pomnik Centrum Zdrowia Dziecka
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Wroclaw, Polonia, 51 124
- Wojewodzki Szpital Specjalistyczny we Wroclawiu
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Zabrze, Polonia, 41-800
- Slaskie Centrum Chorob Serca
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Lisbon, Portogallo, 1169-024
- Uls Sao Jose - Hosp. Santa Marta
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Porto, Portogallo, 4200 319
- Uls Sao Joao - Hosp. Sao Joao
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Kazan', Russia, 420012
- Kazan State Medical University
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Kazan', Russia, 420059
- Kazan State Medical University 1
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Kemerovo, Russia, 650002
- Scientific and Research Institution of Cardiovascular Diseases Complex Problems
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Moscow, Russia, 125373
- Childrens City Clinical Hospital n.a. Bashlyaeva
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Moscow, Russia, 125412
- Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU
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Samara, Russia, 443070
- Samara Regional Clinical Cardiological Dispensary
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Belgrade, Serbia, 11000
- Univerzitetska Dečja Klinika
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A Coruña, Spagna, 15006
- Hosp Univ A Coruna
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Barcelona, Spagna, 08035
- Hosp Univ Vall D Hebron
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Esplugues de Llobregat, Spagna, 08950
- Hosp. Sant Joan de Deu
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Madrid, Spagna, 28046
- Hosp. Univ. La Paz
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Madrid, Spagna, 28009
- Hosp. Gral. Univ. Gregorio Maranon
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Seville, Spagna, 41013
- Hosp. Virgen Del Rocio
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Arizona
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Phoenix, Arizona, Stati Uniti, 85016
- Phoenix Children's Hospital
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California
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Los Angeles, California, Stati Uniti, 90095
- UCLA Medical Center
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San Francisco, California, Stati Uniti, 94158
- UCSF
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Colorado
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Aurora, Colorado, Stati Uniti, 80045
- Childrens Hospital Colorado
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District of Columbia
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Washington D.C., District of Columbia, Stati Uniti, 20010
- Children's National Medical Center
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Florida
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Gainesville, Florida, Stati Uniti, 32610
- Congenital Heart Center of the University of Florida
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Indiana
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Indianapolis, Indiana, Stati Uniti, 46202
- Riley Hospital for Children
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Michigan
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Detroit, Michigan, Stati Uniti, 48201
- Detroit Medical Center
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Ohio
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Cincinnati, Ohio, Stati Uniti, 45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- Childrens Hospital Of Philadelphia
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Texas
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Houston, Texas, Stati Uniti, 77030
- Texas Children's Hospital
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Utah
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Salt Lake City, Utah, Stati Uniti, 84113
- Primary Children's Hospital
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Virginia
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Charlottesville, Virginia, Stati Uniti, 22908
- University of Virginia Division of Pediatric Cardiology
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Gothenburg, Svezia, 416 50
- Drottning Silvias barn- och ungdomssjukhus
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Lund, Svezia, 222 42
- Skanes universitetssjukhus
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Lausanne, Svizzera, 1011
- Centre Hospitalier Universitaire Vaudois CHUV
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Chiang Mai, Tailandia, 50200
- Chiang Mai University Hospital
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Songkhla, Tailandia, 90110
- Songklanagarind hospital
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Kaohsiung City, Taiwan, 813414
- Kaohsiung Veterans General Hospital
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Tainan, Taiwan, 704
- National Cheng Kung University Hospital
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Taipei, Taiwan, 100
- National Taiwan University Hospital
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Adana, Turchia (Türkiye), 01790
- Cukurova Balcali Hospital Application and Research Center
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Ankara, Turchia (Türkiye), 06230
- Hacettepe University Medical Faculty
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Istanbul, Turchia (Türkiye), 34093
- CAPA Istanbul University Medical Faculty
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Istanbul, Turchia (Türkiye), 34303
- Mehmet Akif Ersoy Training and Research Hospital
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Izmir, Turchia (Türkiye), 35020
- Izmir Tepecik Training and Research Hospital
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Izmir, Turchia (Türkiye), 35210
- Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital
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Dnipro, Ucraina, 49006
- Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev
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Dnipro, Ucraina, 49070
- MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
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Kyiv, Ucraina, 04050
- Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH
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Zaporizhzhya, Ucraina, 69063
- MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council
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Budapest, Ungheria, 1096
- Gottsegen György Országos Kardiológiai Intézet
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Hanoi, Vietnam
- Hanoi Medical University Hospital
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Ho Chi Minh City, Vietnam
- Children's Hospital 1
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Ho Chi Minh City, Vietnam, 700000
- Tam Anh Hospital
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Ho Chi Minh City, Vietnam, 700000
- University Medical Center Ho Chi Minh city
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Participants between greater than or equal to (>=) 2 and less than (<) 18 years of age weighing >=9 kilogram (kg) at randomization
- Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's screening
- PAH (World Health Organization [WHO] Group 1), including participants with Down syndrome, of the following etiologies: Idiopathic PAH (IPAH); Heritable PAH (HPAH); PAH associated with congenital heart disease (PAH-associated with congenital heart disease [aCHD]) (PAH with coincidental CHD [that is, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR] and if approved by the BCAC) and Post-operative PAH (persisting / recurring/ developing >=6 months after repair of CHD); Drug or toxin-induced; PAH associated with Human immunodeficiency virus (HIV)
- WHO functional class (FC) II and III
- Participants treated with at least 1 PAH-specific treatment, example, an Endothelin receptor antagonist (ERA) and/or a Phosphodiesterase type-5 (PDE-5) inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to first dose of study intervention
Exclusion Criteria:
- PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis
- PAH associated with Eisenmenger syndrome
- Previous exposure to Uptravi (selexipag)
- Known concomitant life-threatening disease with a life expectancy <12 months
- Pregnant, planning to become pregnant, or lactating
- Known allergies, hypersensitivity, or intolerance to selexipag or its excipients
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Selexipag
Participants will receive selexipag based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Selexipag will be uptitrated during the first 12 weeks until the participants reaches the individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline body-weight category is achieved. Uptitration is followed by a maintenance period after Week 12 until end of treatment (EOT), at the maximum tolerated dose. Participants will continue to receive pulmonary arterial hypertension (PAH)-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
Selexipag tablet will be administered orally.
Altri nomi:
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. |
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Comparatore placebo: Placebo
Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. Matching placebo tablets will be administered orally. |
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Sperimentale: Open-Label Extension Period: Selexipag
Participants with a positive benefit/risk ratio of selexipag for PAH will be offered selexipag in the open label extension period. Participants on selexipag during the double-blind treatment period will continue treatment at their iMTD during the OLEP, for those previously on placebo, the iMTD will uptitrate selexipag during first 12 weeks until participant reaches iMTD. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
Selexipag tablet will be administered orally.
Altri nomi:
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Double-blind Period: Time to Disease Progression
Lasso di tempo: Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Time to disease progression: time from randomization to first Clinical Event Committee (CEC)-confirmed disease progression event occurring between date of randomization until double-blind end date (DBED) + 7 days. Disease progression event as adjudicated by CEC, defined as any of the following: death (all causes); atrial septostomy or Potts' anastomosis, or registration on lung transplant list; hospitalization due to worsening pulmonary arterial hypertension (PAH); clinical worsening of PAH. Clinical worsening of PAH was defined as initiation of new PAH-specific therapy or intravenous diuretics or continuous oxygen use and at least 1 of the following: worsening in World Health Organization (WHO) functional class (FC); new occurrence or worsening: of syncope, of at least 2 PAH symptoms (shortness of breath/dyspnea, chest pain, cyanosis, dizziness/near syncope, or fatigue), of signs of right heart failure not responding to oral diuretics. Kaplan-Meier method was used for estimation. |
Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Double-blind Period: Change in log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 24
Lasso di tempo: Baseline (Day 1), Week 24
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Change in log2 NT-proBNP from baseline to Week 24 was reported. Change from baseline to Week 24 in the central laboratory NT-proBNP (nanograms per liter [ng/L]) value, expressed as the log2-transformed ratio of the Week 24 NT-proBNP value over the baseline value: log2 (Week 24 NT-proBNP divided by Baseline NT-proBNP). Clinically, a reduction from baseline in NT-proBNP (ratio < 1) was considered an improvement. The baseline value was the last non-missing assessment obtained before or on the DB start date (DBSD). |
Baseline (Day 1), Week 24
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Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious AEs (TESAEs)
Lasso di tempo: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Number of participants with TEAEs (included serious and non-serious events) and TESAEs during DB period was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TEAEs were defined as any AE occurring on or after the initial administration of study intervention through the day of last dose in the DB treatment period plus 3 days and/or prior to start of OL study administration. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
Lasso di tempo: Placebo arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 198 weeks); Selexipag arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 212 weeks)
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Number of participants with AEs leading to premature discontinuation of study treatment during DB period was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
Placebo arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 198 weeks); Selexipag arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 212 weeks)
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Double-blind Period: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in vital signs parameters: systolic and diastolic blood pressure during DB period was reported. Vital signs were measured after the participant has rested at least 5 minutes in sitting position. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Vital Signs: Pulse Rate
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in vital signs parameter: pulse rate during DB period was reported. Vital signs were measured after the participant has rested for at least 5 minutes in sitting position. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Growth Parameter: Body Weight
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in growth parameter: body weight during DB period was reported. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Growth Parameter: Height
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in growth parameter: height during DB period was reported. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Number of Participants With Shift From Baseline in Sexual Maturation (Tanner Stage)
Lasso di tempo: Placebo arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Tanner staging were assessed for pubic hair growth and genitalia development (GD) in males (M) and for pubic hair growth and breast development (BD) in females (F) in stages(S) 1 to 5 and missing data. If a participant had reached Tanner stage 5, no further tanner pubertal stage assessment were to be completed. Tanner stage was assessed in F >=8 years; M >=9 years. Pubic hair growth (M and F) stages: S1: No hair, S2: Downy hair, S3: More coarse and curly hair, S4: Adult-like hair quality; S5: Hair extends to medial surface of thighs. BD in females: S1: Nipple raised a little, rest of breast still flat, S2: Breast bud forms, S3: More elevated, outside areola, S4: Increased breast size, S5: Final adult-size breasts. GD in males: S1: Testes, scrotum, and penis about same size, S2: Enlargement of scrotum, testes, and penis, S3: Enlargement of penis, S4: Penis and glands became larger, S5: Genitalia size and shape same an adult male. Categories with at least 1 non-zero data are reported. |
Placebo arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With Treatment-emergent Electrocardiogram (ECG) Abnormalities
Lasso di tempo: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Number of participants with treatment-emergent ECG abnormalities were reported. Any abnormality occurring on or after the initial administration of study intervention through the day of last dose in the DB treatment period plus 3 days was considered to be treatment-emergent. Abnormalities that were not present at baseline were reported. Abnormalities were assessed as per investigator's discretion. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With Treatment-emergent (TE) Marked Laboratory Abnormalities
Lasso di tempo: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Number of participants with TE marked laboratory abnormalities during DB period was reported. TE marked laboratory abnormalities included hemoglobin, platelet count, leukocyte count, potassium, calcium, thyrotropin, thyroxine free and triiodothyronine free. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. If the abnormality was present at baseline, then any post-baseline abnormality was considered treatment-emergent only if the post-baseline abnormality was in a category worse than at baseline. HH, HHH, HHHH = marked abnormally high values; LL, LLL = marked abnormally low values. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Thyroid Stimulating Hormone
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: thyroid stimulating hormone during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Hemoglobin
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: hemoglobin during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Platelets, Leukocytes
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: platelets, leukocytes during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Electrolytes (Sodium, Potassium, Calcium, Bicarbonate and Chloride)
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: electrolytes (sodium, potassium, calcium, bicarbonate and chloride) during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Transaminases (Alanine Aminotransferase [ALT] and Aspartate Aminotransferase [AST])
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: transaminases (ALT and AST) during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Bilirubin
Lasso di tempo: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: bilirubin during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Time to First Clinical Event Committee (CEC)-Confirmed Hospitalization or Death for Pulmonary Arterial Hypertension (PAH)
Lasso di tempo: Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Time to first CEC-confirmed hospitalization or death for PAH was calculated as the onset date of the first CEC-confirmed death or hospitalization due to PAH minus date of randomization+1 day. Kaplan-Meier method was used for estimation. |
Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Double-blind Period: Dose-normalized Steady-state Trough Concentrations (Ctrough,ss,dn) of Selexipag and Its Metabolite ACT-333679 by Age Cohort
Lasso di tempo: Cohort (C) 1: Predose between Week (W) 16 to end of DB treatment period (maximum up to W212); C 2: Predose between Week 16 to end of DB treatment period (maximum up to W198); C 3: Predose between Week 16 to end of DB treatment period (maximum up to W96)
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Dose-normalized trough plasma concentration at steady-state (Ctrough,ss,dn) was defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the PK sampling. Steady-state was considered achieved if the participant has received a stable dose for at least 3 days prior to collection of the plasma sample. PK samples were collected at two protocol-specified visits per participant occurring between Week 16 and end of DB treatment period. Exact visit timing varied by participant. |
Cohort (C) 1: Predose between Week (W) 16 to end of DB treatment period (maximum up to W212); C 2: Predose between Week 16 to end of DB treatment period (maximum up to W198); C 3: Predose between Week 16 to end of DB treatment period (maximum up to W96)
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Double-blind Period: Dose-normalized Steady-state Trough Concentrations (Ctrough,ss,dn) of Selexipag and Its Metabolite ACT-333679 by Body Weight (BW)
Lasso di tempo: BW >=50kg: Predose between W16 to end of DB treatment period (maximum up to W212); BW >=25-<50kg: Predose between W16 to end of DB treatment period (maximum up to W198); BW >=9- <25kg: Predose between W16 to end of DB treatment period (maximum up to W175)
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Dose-normalized steady-state trough concentration (Ctrough,ss,dn) was defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the PK sampling. Steady-state was considered achieved if the participant has received a stable dose for at least 3 days prior to collection of the plasma sample. PK samples were collected at two protocol-specified visits per participant occurring between Week 16 and end of DB treatment period. Exact visit timing varied by participant. |
BW >=50kg: Predose between W16 to end of DB treatment period (maximum up to W212); BW >=25-<50kg: Predose between W16 to end of DB treatment period (maximum up to W198); BW >=9- <25kg: Predose between W16 to end of DB treatment period (maximum up to W175)
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Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Actelion Clinical Trial, Actelion
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie vascolari
- Malattia cardiovascolare
- Malattie delle vie respiratorie
- Malattie polmonari
- Ipertensione
- Ipertensione, polmonare
- Amministrazione dei servizi sanitari
- Qualità, accesso e valutazione dell'assistenza sanitaria
- Qualità dell'assistenza sanitaria
- Indicatori di qualità, assistenza sanitaria
- Standard di cura
- Selexipag
- Proteina PDE5A, umana
Altri numeri di identificazione dello studio
- CR108716
- 2019-002817-21 (Numero EudraCT)
- AC-065A310 (Altro identificatore: Janssen Research & Development, LLC)
- 2022-501012-34-00 (Identificatore di registro: EUCT number)
- 2019 (Sovvenzione/contratto NIH degli Stati Uniti)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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