A prospective, multicenter, open-label, single-arm, Phase 2 study to investigate the safety, tolerability and pharmacokinetics of selexipag in children with pulmonary arterial hypertensio
- Conditions
- 4. PAH belonging to Nice 2013 Updated Classification Group 1 (including Down syndrome) and of one of the following etiologies: - Idiopathic (iPAH)- Heritable (hPAH)- aPAH-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 (PAH aCTD)I27.0Primary pulmonary hypertension
- Registration Number
- DRKS00015024
- Lead Sponsor
- Actelion Pharmaceuticals Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 63
1. Signed and dated informed consent by the parent(s) or LAR(s) AND assent from developmentally capable children.
2. Males or females between = 2 and < 18 years of age with weight = 9 kg.
3. PAH diagnosis confirmed by documented historical RHC performed at any time before subject’s enrollment, and characterized by:
• mPAP = 25 mmHg,
and
• PAWP = 15 mmHg
(in the absence of pulmonary vein obstruction and/or significant lung disease PAWP, can be replaced by LAP or, in absence of mitral stenosis, by LVEDP)
and
• PVRi > 3 WU × m2
4. PAH belonging to Nice 2013 Updated Classification Group 1 (including Down syndrome) and of one of the following etiologies:
• iPAH
• hPAH
• aPAH-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-aCTD
5. WHO FC II to III.
6. Subjects treated with an ERA and/or a PDE-5 inhibitor provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or patients 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 plus 30 days (EOS).
Etiology
1.Subjects with PAH due to portal hypertension, schistosomiasis, 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.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 subjects listed for organ transplantation related to PAH.
12.History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator’s judgment.
Baseline abnormalities
13.Known concomitant life-threatening disease with a life expectancy < 12 months.
14.Uncontrolled thyroid disease as per investigator judgment.
15.Hemoglobin or hematocrit < 75% of the lower limit of normal range.
16.Known severe or moderate hepatic impairment, i.e., Child-Pugh Class B or C [see Appendix 4]
17.Clinical signs of hypotension that in the investigator’s judgment would preclude initiation of a PAH-specific therapy.
18.Subjects with severe renal insufficiency (estimated creatinine clearance < 30 mL/min or serum creatinine > 221 µmol/L).
Pregnancy and breastfeeding
19.Pregnancy (including family planning) or breastfeeding.
Other categories
20.Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations.
21.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.
22.Loss of 250 mL or more of blood within 3 months prior to screening.
23.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).
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint is model-based exposure (AUCt,ss, combined) of selexipag and ACT-333679 corrected for their potency, determined during the 12 week up-titration period
- Secondary Outcome Measures
Name Time Method • AUCt,ss, Cmax,ss and tmax,ss for selexipag and ACT-333679 based on non-compartmental analysis (NCA).<br>• Ctrough, ss on Day 15, and at Weeks 4 and 6 (i.e., Visits 4, 5, 6) for selexipag and ACT-333679