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

NCT ID: NCT04604782

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-20
• Study Completion Date: 2026-12-31

Brief 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

Detailed 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.

Conditions

Myocardial Ischemia; Coronary Artery Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

adolescents aged 12 to <18 years

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

Regadenoson (Rapiscan®): Single i.v. bolus dose in stress rest CMR

children aged 2 to <12 years

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

Regadenoson (Rapiscan®): Single i.v. bolus dose in stress rest CMR

infants aged 1 to <24 months and who weigh at least 3 kg

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

Regadenoson (Rapiscan®): Single i.v. bolus dose in stress rest CMR

Interventions

Regadenoson

Regadenoson (Rapiscan®): Single i.v. bolus dose in stress rest CMR

Intervention Type: DRUG

Other Intervention Names

Rapiscan

Eligibility 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.

• Minimum Eligible Age: 4 Weeks
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Covance

INDUSTRY

Sponsor Role: collaborator

GE Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Thompson, MD, PhD

Role: STUDY_DIRECTOR

GE Healthcare

Locations

Paris Public Hospitals System; Necker Hospital for Sick Children

Paris, , France

Site Status: TERMINATED

Mitera Hospital

Athens, , Greece

Site Status: RECRUITING

Bambino Gesu Children Hospital

Roma, , Italy

Site Status: RECRUITING

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status: NOT_YET_RECRUITING

King's College London, Rayne Institute

London, , United Kingdom

Site Status: RECRUITING

Countries

France; Greece; Italy; United Kingdom

Central Contacts

Michelle Straszacker

Role: CONTACT

michelle.straszacker@gehealthcare.com

+44 (0) 7827845147

Facility Contacts

Aphrodite Tzifa, MD

Role: primary

atzifa@mitera.gr

+30 210 6869788

Maria Giulia Gagliardi, MD, PhD

Role: primary

mgiulia.gagliardi@opbg.net

+39 06 6859 2407

Srinivas Narayan, MD

Role: primary

Srinivas.Narayan@uhbw.nhs.uk

+44 0117 342 8460

Kuberan Pushparajah, MD

Role: primary

kuberan.pushparajah@kcl.ac.uk

+44 (0)7714 989547

Other Identifiers

GE-262-001

Identifier Type: -

Identifier Source: org_study_id