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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04175600




Registration number
NCT04175600
Ethics application status
Date submitted
8/11/2019
Date registered
25/11/2019
Date last updated
8/07/2020

Titles & IDs
Public title
A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension
Scientific title
A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group, Event-Driven, Group-Sequential Study With Open-Label Extension Period to Assess the Efficacy and Safety of Selexipag as Add-On Treatment to Standard of Care in Children Aged >=2 to <18 Years With Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
2019-002817-21
Secondary ID [2] 0 0
CR108716
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension, Pulmonary 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Selexipag
Treatment: Drugs - Placebo

Experimental: 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.

Placebo Comparator: Placebo - Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing.


Treatment: Drugs: Selexipag
Selexipag tablet will be administered orally.

Treatment: Drugs: Placebo
Matching placebo tablets will be administered orally.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Disease Progression - Time to disease progression is the time from randomization up to 7 days after study treatment discontinuation. Disease progression is defined as the first occurrence of either of the following components: 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.
Timepoint [1] 0 0
From randomization up to 7 days after study treatment discontinuation (up to 5 years)
Secondary outcome [1] 0 0
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs - An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are AEs with onset during the intervention 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.
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment - Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Change from Baseline in Systolic and Diastolic Arterial Blood Pressure - Change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
Timepoint [3] 0 0
Baseline up to end of treatment (EOT) (up to 8.3 years)
Secondary outcome [4] 0 0
Change from Baseline in Pulse Rate - Change from baseline in pulse rate to all assessed time points will be reported.
Timepoint [4] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [5] 0 0
Change from Baseline in Body Weight - Change from baseline in body weight to all assessed time points will be reported.
Timepoint [5] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [6] 0 0
Change from Baseline in Height - Change from baseline in height to all assessed time points will be reported.
Timepoint [6] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [7] 0 0
Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points - The sexual maturation change as per Tanner stage will be assessed from baseline to all assessed time points. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs.
Timepoint [7] 0 0
Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8.3 years)
Secondary outcome [8] 0 0
Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities - Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
Timepoint [8] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [9] 0 0
Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities - Percentage of participants with treatment-emergent marked laboratory (serum chemistry [including pregnancy testing and thyroid markers] and hematology) abnormalities will be reported.
Timepoint [9] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [10] 0 0
Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone - Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
Timepoint [10] 0 0
Baseline up to EOT (up to 8.3 years)
Secondary outcome [11] 0 0
Time to First Clinical Event Committee (CEC)-confirmed Hospitalization and Death for PAH - Time to first CEC-confirmed hospitalization and death for PAH is the time (days) from randomization to first occurrence of CEC-confirmed hospitalization for PAH or death due to PAH up to 7 days after study intervention discontinuation.
Timepoint [11] 0 0
Until 7 days after study treatment discontinuation (Up to 8.3 years)
Secondary outcome [12] 0 0
Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679 - Ctrough,ss is defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the pharmacokinetic sampling and will be reported for Selexipag and its metabolite ACT-333679.
Timepoint [12] 0 0
Weeks 16, 24 and every 12 weeks thereafter (up to 8.3 years)

Eligibility
Key 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 screening
Minimum age
2 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland CHILDREN'S HOSPITAL - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
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Belarus
State/province [10] 0 0
Minsk
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussels
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
State/province [14] 0 0
Blumenau
Country [15] 0 0
Brazil
State/province [15] 0 0
Curitiba
Country [16] 0 0
Brazil
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Fortaleza
Country [17] 0 0
Brazil
State/province [17] 0 0
Porto Alegre
Country [18] 0 0
Brazil
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Sao Paulo
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Sofia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Edmonton
Country [22] 0 0
Canada
State/province [22] 0 0
Montreal
Country [23] 0 0
Colombia
State/province [23] 0 0
Bogota
Country [24] 0 0
Colombia
State/province [24] 0 0
Cali
Country [25] 0 0
Colombia
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Floridablanca
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Colombia
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Medellin
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Colombia
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Soledad
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Denmark
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Copenhagen Ø
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France
State/province [29] 0 0
Lille Cedex
Country [30] 0 0
France
State/province [30] 0 0
Marseille Cedex 5
Country [31] 0 0
France
State/province [31] 0 0
Montpellier Cedex 5
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Pessac
Country [34] 0 0
France
State/province [34] 0 0
Toulouse Cedex 9
Country [35] 0 0
Germany
State/province [35] 0 0
Freiburg
Country [36] 0 0
Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Leipzig
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Hungary
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Budapest
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Israel
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Haifa
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Israel
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Ramat Gan
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Italy
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Bologna
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Italy
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Padova
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Italy
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Roma
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Italy
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Torino
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Korea, Republic of
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Seoul
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Korea, Republic of
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Yangsan
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Lithuania
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Vilnius
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Malaysia
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Kuala Lumpur
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Mexico
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Guadalajara
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Mexico
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Mexico
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Mexico
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Monterrey
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Poland
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Gdansk
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Poland
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Kraków
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Poland
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Wroclaw
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Zabrze
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Portugal
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Lisboa
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Portugal
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Porto
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Romania
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Cluj Napoca
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Romania
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Targu Mures
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Romania
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Timisoara
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Russian Federation
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Kazan
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Russian Federation
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Kemerovo
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Samara
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Russian Federation
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Tyumen
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Serbia
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Belgrade
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Spain
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A Coruña
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Spain
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Barcelona
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Spain
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Esplugues de Llobregat
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Spain
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Madrid
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Spain
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Sevilla
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Sweden
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Gothenburg
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Sweden
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Lund
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Switzerland
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Lausanne
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Taiwan
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Tainan
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Taiwan
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Taipei
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Thailand
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Chiang Mai
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Ukraine
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Dnipro
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
State/province [87] 0 0
Zaporizhzhya
Country [88] 0 0
Vietnam
State/province [88] 0 0
Hanoi
Country [89] 0 0
Vietnam
State/province [89] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04175600
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04175600