Overview
This is a multi-centre, open-label, single-dose safety, tolerability and PK-pharmacodynamics (PD) study of the vasodilator regadenoson in 3 paediatric age groups for whom a pharmacologic stress perfusion CMR test is clinically indicated; adolescents aged 12 to <18 years (Cohort A), children aged 2 to <12 years (Cohort B), and infants aged 1 to <24 months and who weigh at least 3 kg (Cohort C). Regadenoson will be used as the pharmacologic stress agent in this study with MPI serving as both surrogate pharmacodynamic marker of the agent (MPR, MBF) and a clinically evaluable examination for the patient
Description
This is a multi-centre, open-label, single-dose safety, tolerability and PK-pharmacodynamics (PD) study of the vasodilator regadenoson in 3 paediatric age groups for whom a pharmacologic stress perfusion CMR test is clinically indicated; adolescents aged 12 to <18 years (Cohort A), children aged 2 to <12 years (Cohort B), and infants aged 1 to <24 months and who weigh at least 3 kg (Cohort C). Regadenoson will be used as the pharmacologic stress agent in this study with MPI serving as both surrogate pharmacodynamic marker of the agent (MPR, MBF) and a clinically evaluable examination for the patient.
At least 54 paediatric patients will be enrolled at approximately 10 centres in Europe: at least 24 adolescents aged 12 to <18 years (Cohort A), at least 18 children aged 2 to <12 years (Cohort B), and at least 12 infants aged 1 to <24 months (Cohort C). The study will be conducted in facilities appropriate for children, and by personnel knowledgeable and skilled in working with paediatric patients. Every attempt will be made to minimise the discomfort of the procedures to the patients. General anaesthesia/sedation with no oral-intake instructions may be used in accordance with age / disease specific requirements of the patient and as deemed necessary by the investigator per standard of care / local practice. In addition, adequate resuscitation equipment and personnel trained and certified in advanced life support must be readily available when regadenoson is administered. A Data Safety Monitoring Board (DSMB) will be in place, and will formally review all safety, efficacy, PK and PD information during the conduct of the study to ensure the safety of patients.
The study will be performed in a sequential manner across the 3 age groups, by decreasing age from adolescents (Cohort A) to children (Cohort B) and to infants (Cohort C). Dosing recommendations for the paediatric population are based on effective dose levels and PK data in adults. Based on a fixed dose of 400 µg regadenoson administered to adults with a mean body weight of 83.8 kg (body weight range: 42 to 161 kg), the effective mean weight-based dose was 4.8 µg/kg (range: 2.5 to 9.5 µg/kg). Within each age group, dosing will be extrapolated from PK-PD data obtained in adults and will be based on body weight-categories to provide approximately the same exposure as 400 µg in adults. The study will start with Cohort A (adolescents). Before the start of dosing in Cohort B, all safety, PK, and PD data obtained in Cohort A will be reviewed by the DSMB. Before the start of dosing in Cohort C, all safety, PK, and PD data obtained in Cohorts A and B will be reviewed by the DSMB.