A Study to Evaluate the Safety and Pharmacokinetics of Regadenoson in Pediatric Patients

• Status: Recruiting
• Trial end date: 2024-08-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GE Healthcare
• Collaborator: Covance
• Treatments: Regadenoson

Criteria

Inclusion Criteria:

• * Male or female adolescent aged from 12 to <18 years (Cohort A) or child aged from 2 to <12 years (Cohort B) or infant aged from 1 to <24 months (Cohort C).

• Patient weighs at least 3 kg.

• Patients who need to undergo a clinically indicated pharmacologic stress perfusion CMR test and who are considered fit for a pharmacological stress perfusion CMR by the investigator. The pharmacologic stress perfusion CMR may be performed in patients for further evaluation of cardiovascular conditions or diseases, such as, but not limited to, Kawasaki disease, congenital heart diseases, congenital coronary abnormalities, and post-cardiac surgery / transplantation, etc.

• Stable medication regimen for at least 7 days prior to dosing. Stable is defined as no addition, discontinuation, or change of any medications (or their doses), that could alter the rate-pressure product (HR x BP).

• Patients and those whose parents or legally authorised representatives are, in the Investigator's view, likely to be compliant and complete the study will be eligible to participate

• Post-menarchal female patients must have a negative urine pregnancy test at screening and at pre-dose on the dosing day.

• Post-menarchal female patients must be practicing abstinence, or be using an effective form of birth control (e.g., intrauterine device, oral contraceptives, contraceptive implants or injections, diaphragm with spermicide, cervical cap, or consort use of condom) for at least 30 days before being enrolled in the study

Exclusion Criteria:

• * Prior allergic reaction to Gd contrast agents and/or regadenoson or any component of its formulation, or to aminophylline or to its components (ethylenediamine and theophylline).

• Standard clinical contraindications to MRI as per institutional guidance, including patients with cochlear implants and implanted cardiac devices, or considered unfit for a pharmacologic stress perfusion CMR test by the investigator.

• All patients will be screened for eGFR within 24 hours before the exam and patients presenting with eGFR <30 mL/min/1.73 m2 (by the Schwartz formula) will be excluded.

• Pregnant or lactating females, or females of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test also required).

• In the judgment of the Investigator, any clinically significant ongoing medical condition (e.g., myocardial infarction, or unstable angina within 5 days, pericardial inflammatory disease, severe cardiac outflow tract obstruction, acutely decompensated heart failure, uncontrolled epilepsy, high risk for seizures, etc.) or clinically significant laboratory abnormality that is considered to potentially jeopardise the patient's safety.

• Patients with 2nd or 3rd degree atrioventricular block or sick sinus syndrome with or without an artificial pacemaker.

• Known or suspected bronchoconstrictive and bronchospastic lung disease either being unstable or requiring active treatment (e.g., wheezing noted on physical exam, frequent exacerbations or active treatment with a bronchodilator or corticosteroids).

• Out of acceptable range sitting or semi-recumbent resting BP or HR (beats per minute [bpm]) at screening as provided below:

1. Acceptable range for BP (systolic / diastolic mmHg):

• For Cohorts A and B: 85-130 / 45-90

• For Cohort C: 80-120 / 40-80 b) Acceptable range for HR:

• For Cohort A: 55 to 100 bpm

• For Cohort B: 60 to 120 bpm

• For Cohort C: 70 to 160 bpm

• Use of any experimental or investigational drug or device within 30 days prior to dosing with study drug

• Consumption of methylxanthine-containing products such as caffeinated coffee, tea, caffeinated soft drinks, cocoa or chocolate in the 48 hours prior to dosing

• Aminophylline or theophylline use within 24 hours, dipyridamole use within 48 hours prior to dosing.

• History of alcohol abuse or drug addiction, as determined by the Investigator

• Currently smokes more than 5 cigarettes or equivalent per day, and if eligible for the study, would not be able to abstain from smoking from midnight prior to dosing until the end of the study period

• Positive urine drug screen at the screening visit, including amphetamines, barbiturates, cannabinoids, cocaine, ethanol and opiates. This will be performed for all patients in Cohort A and those patients at age-appropriate risk in Cohorts B and C, as determined by the investigator.

Note: If the patient is currently receiving prescribed medications containing any of these ingredients, re-screening can only be considered if found acceptable based on the best medical judgement of the investigator and after discussion with the medical monitor. Otherwise, patients with a positive urine drug test will be considered a screen failure.