A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

NCT03492177 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: AC-065A2032022-503042-42-00
• Study Type: interventional
• Target: 63
• Locations: 15 countries
• Sites: 33

Brief Summary

The purpose of this study to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, that leads to similar exposure as adults doses in children from greater than or equal to (\>=) 2 to less than (˂) 18 years of age with Pulmonary Arterial Hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pediatric

Outcome Measures

Primary Outcomes (1)

• Area Under the Plasma Concentration-time Curve Over a Dose Interval at Steady State of Selexipag and Its Metabolite ACT-333679 Combined (AUCτ, ss, Combined)

  AUCτ, ss, combined was defined as the area under the plasma concentration-time curve over one dosing interval at steady state. AUCτ,ss,combined was calculated as 1/38 AUCτ,ss,selexipag plus 37/38 AUCτ,ss,ACT-333679.

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Secondary Outcomes (22)

• Area Under the Plasma Concentration-time Curve Over a Dose Interval of Selexipag at Steady State (AUCτ,ss)

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

• Area Under the Plasma Concentration-Time Curve Over a Dose Interval of ACT-333679 at Steady State (AUCτ,ss)

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

• Maximum Observed Plasma Concentration of Selexipag at Steady State (Cmax,ss)

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

• Maximum Observed Plasma Concentration of ACT-333679 at Steady State (Cmax,ss)

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

• Time to Reach the Maximum Observed Plasma Concentration of Selexipag at Steady State (Tmax,ss)

  Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Study Arms (1)

open label selexipag

EXPERIMENTAL

The first dose of selexipag (Uptravi) will be administered in the evening of Day 1 and will be based on the body weight. Thereafter selexipag will be administered twice daily (morning and evening). Selexipag will be up-titrated during the first 12 weeks, with weekly increments equal to the starting dose until the participants reach their individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline weight category is achieved (which will be 8-fold of the corresponding starting dose). Up-titration is followed by a stable maintenance treatment period from Week 12 to Week 16, at the maximum tolerated dose. Thereafter, participants will be treated with selexipag as long as the treatment is beneficial to the participants, as per investigator's decision.

Drug: selexipag (Uptravi)

Interventions

selexipag (Uptravi) DRUG

Film-coated tablets for oral administration

Also known as: ACT-293987, JNJ-67896049

open label selexipag

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children
• Males or females between greater than or equal to (\>=) 2 and less than (\<) 18 years of age with weight \>= 9 kilograms (kg)
• Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's enrollment
• PAH with one of the following etiologies:
• idiopathic (iPAH),
• heritable (hPAH),
• associated with congenital heart disease (CHD): PAH with co-incidental CHD; post-operative PAH (persisting/ recurring/ developing \>= 6 months after repair of CHD)
• Drug or toxin-induced
• PAH associated with HIV
• PAH associated with connective tissue disease
• Word Health Organization functional class (WHO FC) II to III
• Participants treated with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or participants who are not candidates for these therapies
• Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) from screening up to study drug discontinuation plus 30 days (EOS)

You may not qualify if:

• Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis
• Participants with PAH associated with Eisenmenger syndrome
• Participants with moderate to large left-to-right shunts
• Participants with cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart or pulmonary atresia with ventricular septal defect, as well as Participants with Fontan-palliation
• Participants with pulmonary hypertension due to lung disease
• Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment
• Participants having received prostacyclin (epoprostenol) or prostacyclin analogs (that is, treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are scheduled to receive any of these compounds during the trial
• Treatment with another investigational drug within 4 weeks prior to enrollment
• History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator's judgment
• Uncontrolled thyroid disease as per investigator judgment
• Hemoglobin or hematocrit \< 75 percentage (%) of the lower limit of normal range
• Known severe or moderate hepatic impairment
• Clinical signs of hypotension that in the investigator's judgment would preclude initiation of a PAH-specific therapy
• Participants with severe renal insufficiency
• Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations

Sponsors & Collaborators

• Actelion: lead

Study Sites (34)

Children'S Hospital Cardiac Care Center University Of Colorado

Aurora, Colorado, 80045, United States

Location

University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

State Institution Republican Scientific And Practical Center For Pediatric Surgery

Minsk, 220013, Belarus

Location

Health Institution 4Th City Children'S Clinical Hospital

Minsk, 220118, Belarus

Location

UZ Gent

Ghent, 9000, Belgium

Location

Centre Hospitalier Sainte Justine

Montreal, Quebec, H3T 1C4, Canada

Location

Beijing Anzhen Hospital

Beijing, 100029, China

Location

Shanghai Childrens Medical Center

Shanghai, 200127, China

Location

CHU Arnaud de Villeneuve

Montpellier, 34295, France

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Chu Hopital Des Enfants

Toulouse, 31059, France

Location

Universitätsklinikum Freiburg Zentrum

Freiburg im Breisgau, 70106, Germany

Location

Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Felnott kardiologiai osztaly

Budapest, 1096, Hungary

Location

Schneider Children's Medical Center

Petach Tikvah, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Sarawak Heart Center

Kota Samarahan, 94300, Malaysia

Location

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, 50400, Malaysia

Location

Wojewodzki Szpital Specjalistyczny We Wroclawiu

Wroclaw, 51 124, Poland

Location

Kazan State Medical University

Kazan', 420059, Russia

Location

Scientific and Research Institution of Cardiovascular Diseases Complex Problems

Kemerovo, 650002, Russia

Location

Moscow Scientific Research Institute For Pediatrics And Childrens Surgery Of Rosmedtechnologies

Moscow, 125412, Russia

Location

Saint Petersburg State Pediatric Medical University

Saint Petersburg, 194100, Russia

Location

Almazov National Medical Research Center Of The Ministry Of Health Of The Russian Federation

Saint Petersburg, 197341, Russia

Location

Samara Regional Clinical Cardiological Dispensary

Samara, 443070, Russia

Location

Univerzitetska Dečja Klinika

Belgrade, 11000, Serbia

Location

Institut Za Zdravstvenu Zastitu Majke I Deteta Srbije Dr Vukan Cupic

Belgrade, 11070, Serbia

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Municipal Enterprise Of The Dnipropetrovsk Regional Council

Dnipro, 49070, Ukraine

Location

State Institution Of The Ministry Of Health Of Ukraine

Kiev, 04050, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, 79010, Ukraine

Location

Municipal Institution Of The Zaporizhzhya Regional Council

Zaporizhzhya, 69063, Ukraine

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• Beghetti M, Axelsen LN, Borissoff JI, Farhan M, Grill S, Leng S, Russu A, Lesage C, Remenova T, Hsu Schmitz SF, Moledina S. A Prospective, Multicenter, Open-Label, Single-Arm Phase 2 Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Selexipag in Children With Pulmonary Arterial Hypertension. Chest. 2026 May;169(5):1330-1344. doi: 10.1016/j.chest.2025.12.013. Epub 2025 Dec 20.

  PMID: 41429287 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

selexipag

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Scientist
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Catherine Boisson

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 10, 2018
• Study Start: July 23, 2018
• Primary Completion: March 28, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 5, 2026
• Results First Posted: April 19, 2023

Record last verified: 2026-06

Locations

US (3); DE (1); GB (1); BE (2); CA (1); RU (6); TW (2); MY (2); UA (4); HU (1); SE (2); IL (2); CN (2); PL (1); FR (3)