A clinical study to confirm the doses of selexipag to be used in children with pulmonary arterial hypertensio
- Conditions
- Pulmonary arterial hypertensionMedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-000145-39-DE
- Lead Sponsor
- Actelion Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 < 18 years of age at Baseline / Enrollment / Visit 2 weighing = 9 kg.
3. PAH diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before the participant’s enrollment
4. 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
• PAH associated with HIV
• PAH associated with connective tissue disease
5. Word Health Organizaition functional class (WHO FC) II to III.
6. 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.
7. 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 + 30 days (EOS).
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Etiology
1. Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis.
2. Participants with PAH associated with Eisenmenger syndrome.
3. Participants with moderate to large left-to-right shunts.
4. 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 subjects with Fontan palliation.
5. Participants with PH due to lung disease and/or hypoxia. For subjects with Down syndrome, exclusion of lung disease and hypoxia causing PH should be documented (e.g., computed tomography scan, polysomnography, lung function tests).
Treatment and intervention
6. Previous treatment with Uptravi® (selexipag) within 2 weeks prior to enrollment.
7. Participants having received prostacyclin (epoprostenol) or prostacyclin analogs2 (i.e., treprostinil, iloprost, beraprost) within 2 months prior to enrollment or who are scheduled to receive any of these compounds during the trial.
8. Treatment with another investigational drug within 4 weeks prior to enrollment.
9. Treatment with strong and moderate inhibitors of CYP2C8 (e.g., gemfibrozil, clopidogrel, deferasirox, teriflunomide) within 2 weeks prior to enrollment until the last dose of selexipag + 3 days.
10. Treatment with inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, and fluconazole) are prohibited from 2 weeks prior to enrollment and until the last dose of selexipag + 3 days.
11. Any PAH-related surgical intervention planned, or participants listed for organ transplantation related to PAH.
12. History or current suspicion of intussusception or ileus or gastrointestinal obstruction, per investigator’s judgment.
Baseline abnormalities
13. Known concomitant life-threatening disease with a life expectancy < 12 months.
14. Uncontrolled thyroid disease, per investigator’s judgment.
15. Hemoglobin or hematocrit < 75% of the lower limit of normal range.
16. 1 Moderate or severe hepatic impairment, eg, Child-Pugh Class B or
C [see Appendix 4].
17. Clinical signs of hypotension that, in the investigator’s judgment, would preclude the initiation of a PAH-specific therapy.
18. Participants with severe renal insufficiency (estimated creatinine clearance < 30 mL/min or serum creatinine > 221 µmol/L).
19. Severe coronary heart disease or unstable angina as assessed by the investigator.
20. Myocardial infarction within the last 6 months prior to enrollment.
21. Decompensated cardiac failure if not under close supervision.
22. Severe arrhythmias as assessed by the investigator.
23. Cerebrovascular events (e.g., transient ischemic attack, stroke) within the last 3 months prior to enrollment.
24. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to PH.
Pregnancy and breastfeeding
25. Pregnancy (including family planning) or breastfeeding.
Other categories
26. Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations.
27. Drug or substance abuse, or any condition that, in the opinion of the investigator, may prevent compliance with the protocol or adherence to study treatment.
28. Loss of 250 mL or more of blood within 3 months prior to screening.
29. History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interf
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, that 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: <br>- 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 Outcome Measures
Name Time Method