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.

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

Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)

Lung Conditions

Heart and lung conditions

The selection of the starting dose for pediatric participants is based on the PK extrapolation from adults, taking into account the children body weight category, in order to lead to an exposure similar to that in adult PAH participants at a starting dose of 200 micrograms (mcg). As in adults, selexipag will be up-titrated to the individual maximum tolerated dose (iMTD) during the first 12 weeks. Approximately 60 participants will be enrolled in 3 different age cohorts to obtain at least 45 participants with evaluable PK profiles: Cohort 1: >= 12 to < 18 years of age, Cohort 2: >= 6 to < 12 years of age, Cohort 3: >= 2 to < 6 years of age. In each age cohort the starting dose will depend on the body weight. Enrollment will start with both Cohort 1 and Cohort 2. After completion of PK assessments in at least 15 participants from Cohort 1 at Week 12, a first interim analysis will be conducted to establish the dose-exposure relationship using a population PK model. The PK data from any participants in Cohort 2 who have completed their PK assessments at this time will be included in this first interim analysis. Results of this model-based analysis will be used to confirm or adjust the selexipag doses initially selected. Enrollment of Cohort 3 (children >= 2 to < 6 years of age) will start once the appropriate doses have been confirmed in a second interim analysis of PK data from Cohorts 1 and 2, and if there is no safety concern based on review by an Independent Data Monitoring Committee (IDMC).

selexipag (Uptravi)

A Prospective, Multicenter, Open Label, Single Arm, Phase 2 Study to Investigate the Safety, Tolerability and Pharmacokinetics of Selexipag in Children With Pulmonary Arterial Hypertension

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.

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.

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.

The selection of the starting dose for pediatric participants is based on the PK
      extrapolation from adults, taking into account the children body weight category, in order to
      lead to an exposure similar to that in adult PAH participants at a starting dose of 200
      micrograms (mcg). As in adults, selexipag will be up-titrated to the individual maximum
      tolerated dose (iMTD) during the first 12 weeks. Approximately 60 participants will be
      enrolled in 3 different age cohorts to obtain at least 45 participants with evaluable PK
      profiles: Cohort 1: >= 12 to < 18 years of age, Cohort 2: >= 6 to < 12 years of age, Cohort
      3: >= 2 to < 6 years of age. In each age cohort the starting dose will depend on the body
      weight. Enrollment will start with both Cohort 1 and Cohort 2. After completion of PK
      assessments in at least 15 participants from Cohort 1 at Week 12, a first interim analysis
      will be conducted to establish the dose-exposure relationship using a population PK model.
      The PK data from any participants in Cohort 2 who have completed their PK assessments at this
      time will be included in this first interim analysis. Results of this model-based analysis
      will be used to confirm or adjust the selexipag doses initially selected. Enrollment of
      Cohort 3 (children >= 2 to < 6 years of age) will start once the appropriate doses have been
      confirmed in a second interim analysis of PK data from Cohorts 1 and 2, and if there is no
      safety concern based on review by an Independent Data Monitoring Committee (IDMC).

Children'S Hospital Cardiac Care Center University Of Colorado

University of Iowa Hospital

Seattle Children's Hospital

State Institution Republican Scientific And Practical Center For Pediatric Surgery

Health Institution 4Th City Children'S Clinical Hospital

UZ Gent

Centre Hospitalier Sainte Justine

Beijing Anzhen Hospital

Shanghai Children's Medical Center

CHU Arnaud de Villeneuve

Hôpital Necker - Enfants Malades

Chu Hopital Des Enfants

Universitätsklinikum Freiburg Zentrum

Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály

Schneider Children's Medical Center

Sheba Medical Center

Institut Jantung Negara (National Heart Institute)

Sarawak General Hospital

Wojewodzki Szpital Specjalistyczny We Wroclawiu

Kazan State Medical University

Federal State Budget Scientific Institution

Moscow Scientific Research Institute For Pediatrics And Childrens Surgery Of Rosmedtechnologies

Samara Regional Clinical Cardiological Dispensary

Federal State Budgetary Institution

Saint Petersburg State Pediatric Medical University

Univerzitetska Dečja Klinika

Institut Za Zdravstvenu Zaštitu Majke I Deteta Srbije ''Dr Vukan Čupić''

National Cheng Kung University Hospital

National Taiwan University Hospital

Municipal Enterprise Of The Dnipropetrovsk Regional Council

State Institution Of The Ministry Of Health Of Ukraine

Lviv Regional Clinical Hospital

Municipal Institution Of The Zaporizhzhya Regional Council

Great Ormond Street Hospital

Shanghai Childrens Medical Center

Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Felnott kardiologiai osztaly

Sarawak Heart Center

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

Institut Za Zdravstvenu Zastitu Majke I Deteta Srbije Dr Vukan Cupic

Scientific and Research Institution of Cardiovascular Diseases Complex Problems

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures