Pulmonary arterial hypertension MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Actelion Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children. 2. Males or females between = 2 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Etiology 1. Subjects with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis. 2. Subjects with PAH associated with Eisenmenger syndrome. 3. Subjects with moderate to large left-to-right shunts. 4. Subjects 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 subjects with Fontan-palliation. 5. Subjects with pulmonary hypertension due to lung disease (e.g., bronchopulmonary dysplasia). Treatment and intervention 6. Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment. 7. Subjects having received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are scheduled to receive any of these compounds during the trial. 8. Treatment with another investigational drug within 4 weeks prior to enrollment. 9. History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator’s judgment. Baseline abnormalities 10. Uncontrolled thyroid disease as per investigator judgment. 11. Hemoglobin or hematocrit 221 µmol/L). Other categories 15. Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations. 16. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study treatment(s) (e.g., cholecystectomy). 17. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, which leads to similar exposures as adult doses in children from = 2 to < 18 years of age, with pulmonary arterial hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population.;Secondary Objective: To evaluate the safety and tolerability of selexipag in children from = 2 to < 18 years of age with PAH.;Primary end point(s): Primary pharmacokinetic (PK) endpoint: - Model-based exposure (AUCt,ss, combined) of selexipag and ACT-333679 corrected for their potency, determined during the 12 weeks up-titration period.;Timepoint(s) of evaluation of this end point: - PK sampling at Weeks 1, 2, 4, 6 and 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary PK endpoints: - Area under the plasma concentration-time curve over a dose interval at steady state (AUCt,ss), maximum concentration at steady state (Cmax,ss), time to reach Cmax,ss (tmax,ss) for selexipag and ACT-333679, based on non-compartmental analysis (NCA). -Ttrough concentration at steady state (Ctrough, ss) for selexipag and ACT-333679. Safety endpoints • Treatment-emergent AEs (TEAEs), treatment-emergent serious adverse events (TESAEs) and treatment-emergent deaths (all causes), AEs leading to permanent discontinuation of study drug. • Treatment-emergent marked laboratory abnormalities and ECG abnormalities up to EOT+ 3 days. • Change from baseline up to EOT + 3 days in: - selected hematology and blood chemistry laboratory variables. - TSH - Vital signs (blood pressure, heart rate) - Height and body mass index - Sexual maturation (Tanner stage) ;Timepoint(s) of evaluation of this end point: - AUCt,ss, cmax,ss, tmax,ss: PK sampling at Weeks 1, 2, 4, 6 and 12 - Ctrough: PK sampling at Weeks 2, 4,and 6 - TEAEs, TESAEs,treatment emergent deaths and AEs leading to permanent discontinuation: continuously from Day 1 up to 3 days after the end of treatment - Tanner stage: at screening (baseline), Week 16 and every 6 months after the first 12 months - Other safety endpoints: on Day 1 (baseline), Week 12 and Week 16, then every 3 months during the first 12 months and every 6 months thereafter up to the end of treatment visit, with additional timepoints for vital signs (Week 4), ECG (Weeks 1 & 4), laboratory tests (Week 4), TSH (Weeks 4 & 8) | — |
Countries
Belarus, Belgium, Canada, China, France, Germany, Hungary, Israel, Italy, Malaysia, Netherlands, Poland, Romania, Russian Federation, Serbia, Singapore, Taiwan, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactClinical Trial Disclosure Desk
Actelion Pharmaceuticals Ltd
Outcome results
None listed