Clinical trial NCT05731492: A Study of Macitentan in Children Below 2 Years of Age
Official title: A Multicenter, Open-label, Single-arm Study to Assess the Pharmacokinetics and Safety of Macitentan in Children Aged 1 Month to <2 Years With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Arterial Hypertension, Pulmonary
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2023-02-16
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to learn what happens to macitentan and its active metabolite (aprocitentan) in the body of children aged between 1 month and 2 years.


Eligibility criteria: Inclusion Criteria:

* Pulmonary arterial hypertension (PAH): 1) including participants with Down syndrome. Diagnosis must have been confirmed by (historical, any time before screening) right heart catheterization mean pulmonary arterial pressure (mPAP) greater than or equal to (\>=) 25 millimeter of mercury (mmHg), pulmonary arterial wedge pressure (PAWP) less than or equal to (=\<)15 mmHg, pulmonary vascular resistance index greater than (\>) 3 Wood units \* meter square (m\^2) where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced left atrium pressure or left ventricular end diastolic pressure (in the absence of mitral stenosis) assessed by heart catheterization. a) Idiopathic PAH, or b) Heritable PAH, or c) PAH associated with congenital heart disease: i) Eisenmenger syndrome (Qp/Qs less than (\<) 1.5 and saturation of peripheral oxygen ≤ 90 percent (%) measured by pulse oximetry at room air), or ii) Inoperable open left-to-right shunts (with a Pulmonary vascular resistance \[PVR\] \> 8 WU and Qp/Qs \<2), or iii) Co-incidental shunt (that is, not explaining hemodynamically the presence of PAH), or iv) Post-operative PAH (persisting/recurring/developing ≥ 6 months after repair of shunt), or d) Drug or toxin induced PAH, or e) PAH associated with Human immunodeficiency viruses (HIV)
* World Health Organization Functional Class (WHO FC) I, II, or III
* PAH-specific treatment-naive participants or participants on PAH specific monotherapy or combination of 2 therapies. Use of macitentan before or during screening is allowed
* Body weight of greater than or equal to (\>=) 3.5 kilogram (kg)
* Parent(s) (preferably both if available or as per local requirements) or participant's legally designated representative must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and is/are willing to allow the child to participate in the study

Exclusion Criteria:

* PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
* Persistent pulmonary hypertension of the newborn
* The following congenital cardiac abnormalities: a) Cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, pulmonary atresia with ventricular septal defect, unless operatively repaired and with no residual shunt. b) Univentricular heart and/or participants with Fontan-palliation
* Pulmonary hypertension due to lung disease
* Known diagnosis of bronchopulmonary dysplasia

Primary outcomes:
measure: Trough Concentration of Macitentan and its Active Metabolite Aprocitentan at Week 4 in Steady-State
timeFrame: Predose (at Week 4)
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 1.5 years
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 1.5 years
measure: Number of Participants with AEs Leading to Premature Discontinuation of Macitentan
timeFrame: Up to 1.5 years
measure: Number of Participants with Adverse Event of Special Interests (AESIs)
timeFrame: Up to 1.5 years
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to 1.5 years
measure: Number of Participants with Change from Baseline in Clinical laboratory Values.
timeFrame: Up to 1.5 years
measure: Change from Baseline in Blood Pressure
timeFrame: Up to 1.5 years
measure: Change From Baseline in Heart Rate
timeFrame: Up to 1.5 years
measure: Change From Baseline in Body Weight
timeFrame: Up to 1.5 years
measure: Change From Baseline in Length
timeFrame: Up to 1.5 years
measure: Change from Baseline in Height
timeFrame: Up to 1.5 years
measure: Plasma Concentration of Macitentan and its Active Metabolite (Aprocitentan) for Macitentan Naive Participants
timeFrame: At 2, 5, and 24 hours after the first dose of macitentan on Day 1
measure: Trough Concentrations of Macitentan and its Active Metabolite Aprocitentan at Week 8 in Steady-State Conditions
timeFrame: Predose (at Week 8)
Other outcomes:
Locations:
city: Freiburg im Breisgau
country: Germany
facility: Universitatsklinikum Freiburg
city: Goettingen
country: Germany
facility: Universitatsmedizin Gottingen
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny We Wroclawiu
Study officials:
affiliation: Actelion
name: Actelion Pharmaceuticals Ltd Clinical Trial
role: STUDY_DIRECTOR
References: