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. MedDRA version: 20.1 Leve
Conditions
Sponsors
GE Healthcare Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be included in the study if they meet all of the following criteria: 1. Male or female adolescent aged from 12 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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). 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. 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. 4. Pregnant or lactating females, or females of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test also required). 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. 6. Patients with 2nd or 3rd degree AV block or sick sinus syndrome with or without an artificial pacemaker. 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). 8. Out of acceptable range sitting or semi-recumbent resting BP or HR (beats per minute [bpm]) at screening as provided below: a) 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 9. Use of any experimental or investigational drug or device within 30 days prior to dosing with study drug. 10. Consumption of methylxanthine-containing products such as caffeinated coffee, tea, caffeinated soft drinks, cocoa or chocolate in the 48 hours prior to dosing. 11. Aminophylline or theophylline use within 24 hours, dipyridamole use within 48 hours prior to dosing. 12. History of alcohol abuse or drug addiction, as determined by the Investigator. 13. 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. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of a single, body-weight (weight category) adjusted intravenous (i.v.) bolus dose of regadenoson in paediatric patients aged 1 month to <18 years and who weigh at least 3 kg. 2. To characterise the pharmacokinetics (PK) of a single, body-weight (weight category) adjusted i.v. dose of regadenoson and the effects on heart rate (HR) in 3 paediatric populations: adolescents aged 12 to <18 years, children aged 2 to <12 years, and infants aged 1 to <24 months, and who weigh at least 3 kg.;Secondary Objective: 1. To determine the relationship between regadenoson PK variables/exposure and changes in HR, including impact of patient factors. 2. To determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass perfusion magnetic resonance imaging (MRI) and quantitative myocardial perfusion reserve (MPR) analysis.;Primary end point(s): Primary Safety Endpoints: Occurrence of AEs, including AEs of special interest (AESIs), changes in physical examination, vital signs (BP, HR, oxygen saturation, body temperature), ECG evaluation, clinical laboratory tests (serum chemistry), and post-regadenoson-dosing concomitant medications. Primary Pharmacokinetic Endpoints: For Cohort A, plasma samples for measurement of regadenoson concentrations will be collected at 1, 3, 5, 10, and 20 minutes, and at 1 and 2 hours post-regadenoson dose. Concentration-time profiles will be evaluated using compartmental methods and a population approach with mixed-effect modelling. 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. For Cohorts B and C, population PK modelling similar to that used in Cohort A will be applied. The frequency, time points, and/or sampling windows of blood draws for PK will be determined after analysis of the da | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass perfusion CMR and the MPR starting at 2 minutes after regadenoson injection will be assessed. The quantitative CMR endpoint (MPR) will be assessed in a central read at the end of the study by an independent reader blinded to the clinical outcome/management decisions of the patient.;Secondary end point(s): 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]). | — |
Countries
France, Greece, Italy, United Kingdom
Contacts
Public ContactClinical Trial Information
GE Healthcare Ltd.
Outcome results
None listed