REGADENOSON for Myocardial perfusion abnormalities | Kawasaki disease | Congenital heart disease | Post-cardiac surgery/transplantation

Inclusion criteria

• {"criterion_text":"- 1. Male or female patient aged 2 to <18 years.\n- 2. Patient weighs at least 6 kg.\n- 3. 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.\n- 4. 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 × BP).\n- 5. 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.\n- 6. Post-menarcheal female patients must have a negative urine pregnancy test at screening and at pre-dose on the dosing day.\n- 7. Post-menarcheal female patients and male 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.\n- 8. Parents or legally authorised representatives have signed the Informed Consent Form for this study approved by the Ethics Committee or the Institutional Review Board (IRB) for the patient to participate in the study indicating that the patient (and/or a legally acceptable representative) has been informed of all pertinent aspects of the study, and, for patients who are able, have signed age-appropriate paediatric assent."}

Exclusion criteria

• {"criterion_text":"- Patients must be excluded from participating in this study if they meet any of the following criteria: 1. 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).\n- 2. 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.\n- 3. 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.\n- 4. Pregnant or lactating females or females of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test also required).\n- 5. 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.\n- 6. Patients with 2nd or 3rd degree atrioventricular block or sick sinus syndrome with or without an artificial pacemaker.\n- 7. 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).\n- 8. Out of acceptable range sitting or semi-recumbent resting BP or HR (beats per minute [bpm]) at screening and dosing day as provided below: a) Acceptable range for BP (systolic / diastolic mmHg): 85 to 130 / 45 to 90 b) Acceptable range for HR: 55 to 100 bpm for 12 to <18 years old, and 60 to 120 bpm for 2 to <12 years old.\n- 9. Use of any experimental or investigational drug or device within 30 days prior to dosing with study drug.\n- 10. Consumption of methylxanthine-containing products such as caffeinated coffee, tea, caffeinated soft drinks, cocoa, or chocolate in the 48 hours prior to dosing.\n- 11. Aminophylline or theophylline use within 24 hours, dipyridamole use within 48 hours prior to dosing.\n- 12. History of alcohol abuse or drug addiction.\n- 13. Positive urine drug screen at the screening visit, including amphetamines, barbiturates, cannabinoids, cocaine, ethanol and opiates, unless it is a prescribed medication containing any of these ingredients, the investigator finds it acceptable, and after agreement from the Sponsor medical monitor.\n- 14. 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."}

Primary endpoints

• {"endpoint_text":"- Primary Safety Endpoints: Occurrence of AEs, including AEs of special interest (AESIs), changes in physical examination, vital signs (BP, HR, RR, oxygen saturation, body temperature), ECG evaluation, clinical laboratory tests (serum chemistry), and post-regadenoson dosing concomitant medications. Evaluation will begin at the time of patient consent for the trial and continue through completion of the study or early withdrawal/termination. Collection of AEs will continue through study completion","definition_or_measurement_approach":"Safety assessed by collection of adverse events (including AESIs), physical exam findings, vital signs (BP, HR, RR, O2 saturation, temperature), ECG evaluations, clinical laboratory tests (serum chemistry) and concomitant medications. Evaluation begins at consent and continues through study completion or early withdrawal."}
• {"endpoint_text":"- or withdrawal/termination after the final PK blood draw (at 2 hours post-regadenoson dose) with an additional recommended observation as considered appropriate based on the patient’s condition and/or local standard of care practice and during the follow-up phone call or clinic visit at 48 hours (±12 hours).","definition_or_measurement_approach":"Defines timing of withdrawal/termination relative to PK sampling; includes recommended additional observation based on patient condition and a follow-up phone call or clinic visit at 48 hours (±12 hours) post-dose."}
• {"endpoint_text":"- Primary Pharmacokinetic Endpoints: The plasma samples for measurement of regadenoson concentrations will be collected at 1, 3, 5, 10, and 20 minutes and 1 and 2 hours post-regadenoson dose. Concentration-time profiles will be evaluated using compartmental methods and a population approach with mixed-effect modelling.","definition_or_measurement_approach":"PK measured via plasma regadenoson concentrations at 1, 3, 5, 10 and 20 minutes, and 1 and 2 hours post-dose. Analysis using compartmental methods and population mixed-effects modelling to generate concentration–time profiles and PK parameters."}
• {"endpoint_text":"- The effect of patient factors (such as, but not limited to, age, gender, body weight, height, body mass index [BMI], body surface area [BSA], renal function [SCr, eGFR]) on the PK variables will be assessed.","definition_or_measurement_approach":"Assessment of covariate effects on PK variables (e.g., age, sex, weight, height, BMI, BSA, renal function SCr and eGFR) through PK modelling and exposure-response analyses."}

Secondary endpoints

• {"endpoint_text":"- \"Secondary Pharmacodynamic Endpoints: The relationship between regadenoson PK variables/exposure and changes in HR will be assessed, including impact of patient factors (e.g., age, gender, body weight, height, BMI, BSA, renal function [SCr, eGFR]).\"","definition_or_measurement_approach":"Assess relationship between regadenoson exposure and heart rate (HR) changes; includes evaluating impact of patient covariates (age, gender, weight, height, BMI, BSA, renal function) on PD response (HR). HR measured serially around dosing; correlated with PK exposures."}

France

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

19-08-2025

Processing Time Days

406

Number Of Sites

1

Number Of Participants

1

Greece

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

20-08-2025

Processing Time Days

407

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

491

Number Of Sites

2

Number Of Participants

1

Primary sponsor

Full Name

GE Healthcare Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Third parties

• {"country":"United States","full_name":"National Medical Services Inc.","duties_or_roles":"Clinical chemistry","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Transportation of lab kits and samples; Clinical Chemistry.","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Fortrea Development Ltd. Branch Of Foreign Company","duties_or_roles":"","organisation_type":"Pharmaceutical company"}