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

NCT04604782 | Recruiting Phase 1 DMC

• 1 other identifier: GE-262-001
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 5

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

Conditions

Myocardial Ischemia; Coronary Artery Disease

Outcome Measures

Primary Outcomes (10)

• Occurrence of Adverse Events (AEs) following administration of Regadenoson

  An overall summary of AEs, SAEs, and Regadenoson-emergent AEs will be presented, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class and preferred term.

  70 hours after Regadenoson administration

• Changes in physical examinations following administration of Regadenoson

  The number of patients with changes in physical examination status from normal at baseline to abnormal at each post-administration time point will be summarized.

  Baseline and 2 hours after Regadenoson administration

• Changes in physical examinations following administration of Regadenoson

  The percentage of patients with changes in physical examination status from normal at baseline to abnormal at each post-administration time point will be summarized.

  Baseline and 2 hours after Regadenoson administration

• Changes in oxygen saturation following administration of Regadenoson

  The occurrence of post-administration vital sign values outside the normal limits will be summarized.

  Baseline, 15 and 5 minutes before Regadenoson administration and 1, 3, 6, 10, 15, 30 minutes and 1, 2 hours after Regadenoson administration

• Changes in blood pressure in mmHg following administration of Regadenoson

  The occurrence of post-administration vital sign values outside the normal limits will be summarized.

  Baseline, 15 and 5 minutes before Regadenoson administration and 1, 3, 6, 10, 15, 30 minutes and 1, 2 hours after Regadenoson administration

• Changes in heart rate as bpm following administration of Regadenoson

  The occurrence of post-administration vital sign values outside the normal limits will be summarized.

  Baseline, 15 and 5 minutes before Regadenoson administration and 1, 3, 6, 10, 15, 30 minutes and 1, 2 hours after Regadenoson administration

• Changes in body temperature (as degree C) following administration of Regadenoson

  The occurrence of post-administration body temperature values outside the normal limits will be summarized by counts and percentages by age group and actual dose.

  Baseline and 2 hours after Regadenoson administration

• Change from baseline in the results of 12-lead electrocardiograms (ECGs) following administration of Regadenoson

  Descriptive statistics will be used to describe the observed values and change from baseline for ECG intervals (RR, QT, QTcF\[Fridericia\])

  Baseline, 1 and 2 hours after Regadenoson administration

• Changes in serum chemistry following administration of regadenoson

  The occurrence of post-administration clinical laboratory values outside the normal limits will be summarized.

  Baseline and 2 hours after Regadenoson administration

• Time changes of regadenoson blood concentrations (ng/mL) with a single, body-weight adjusted i.v. dose in 3 paediatric populations: adolescents 12 to <18 years,children 2 to <12 years, and infants 1 to <24 months, and who weigh at least 3kg.

  Blood samples for PK assessment will be collected and processed for measurement of Regadenoson blood concentrations. Concentration-time profiles will be evaluated using compartmental methods and a population approach with mixed-effect modelling. A summary will be listed by patient and summarized by age group and actual dose at each time point.

  1, 3, 5, 10, and 20 minutes and 1 and 2 hours post Regadenoson administration

Secondary Outcomes (3)

• Determine the correlation between regadenoson PK concentration (ng/mL) and changes in HR (bpm), including impact of patient factors.

  1, 3, 5, 10, and 20 minutes and 1 and 2 hours post Regadenoson administration

• Determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass perfusion magnetic resonance imaging (MRI).

  1 hour post Regadenoson administration.

• Determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass quantitative myocardial perfusion reserve (MPR) analysis.

  1 hour post Regadenoson administration.

Study Arms (3)

adolescents aged 12 to <18 years

EXPERIMENTAL

Drug: Regadenoson

children aged 2 to <12 years

EXPERIMENTAL

Drug: Regadenoson

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

EXPERIMENTAL

Drug: Regadenoson

Interventions

Regadenoson DRUG

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

Also known as: Rapiscan

adolescents aged 12 to <18 years; children aged 2 to <12 years; infants aged 1 to <24 months and who weigh at least 3 kg

Eligibility Criteria

• Age: 4 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \* 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

You may not qualify if:

• \* 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:
• 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

Sponsors & Collaborators

• GE Healthcare: lead
• Covance: collaborator

Study Sites (5)

Paris Public Hospitals System; Necker Hospital for Sick Children

Paris, 75015, France

TERMINATED

Mitera Hospital

Athens, 15123, Greece

COMPLETED

Bambino Gesu Children Hospital

Roma, 00165, Italy

RECRUITING

Bristol Royal Hospital for Children

Bristol, BS28BJ, United Kingdom

NOT YET RECRUITING

King's College London, Rayne Institute

London, SE1 7EH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Myocardial Ischemia; Coronary Artery Disease

Interventions

regadenoson

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• David Thompson, MD, PhD

  GE Healthcare

  STUDY DIRECTOR

Central Study Contacts

Michelle Straszacker

CONTACT

+44 (0) 7827845147; michelle.straszacker@gehealthcare.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 27, 2020
• Study Start: May 20, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

GR (1); GB (2); IT (1); FR (1)