A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension
Selexipag is available for the treatment of pulmonary arterial hypertension (PAH) in adults in various countries. The efficacy of selexipag to delay disease progression was shown in a previous pivotal study conducted in 1156 adult patients with PAH. Given the similarities in the functional changes of PAH in children and adults, it is expected that children suffering from PAH could benefit from treatment with selexipag. The aim of the present study is to confirm the doses of selexipag to be used in pediatric patients with PAH older than 2 years. To fulfill this aim, blood levels of selexipag (pharmacokinetic assessments) as well as the safety, and tolerability of selexipag in children with PAH will be assessed.
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|Eligible Ages||2 Years - 18 Years|
- - Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children.
- - Males or females between ≥ 2 and < 18 years of age with weight ≥ 9 kg.
- - PAH diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before subject'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.
- - Subjects 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 patients 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).
- - Subjects with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis.
- - Subjects with PAH associated with Eisenmenger syndrome.
- - Subjects with moderate to large left-to-right shunts.
- - 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.
- - Subjects with pulmonary hypertension due to lung disease.
- - Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment.
- - 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.
- - 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% 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.
- - Subjects with severe renal insufficiency.
- - Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations.
- - 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).
- - Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Principal Investigator Affiliation||Actelion|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Countries||Belarus, France, Germany, Hungary, Israel, Malaysia, Poland, Russian Federation, Serbia, Taiwan, Ukraine, United Kingdom, United States|
The disease, disorder, syndrome, illness, or injury that is being studied.
|Pulmonary Arterial Hypertension|
The selection of the starting dose for pediatric patients is based on the pharmacokinetic (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 patients at a starting dose of 200 microgram (μg). As in adults, selexipag will be up-titrated to the individual maximum tolerated dose (iMTD) during the first 12 weeks. Approximately 55 subjects will be enrolled in 3 different age cohorts to obtain at least 40 subjects 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 subjects from Cohort 1 at Week 12, a first interim analysis will be conducted to establish the dose-exposure relationship using a population PK model. 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).
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