Gadovist as diagnostic imaging agent is approved only for adult patients. Diseases usually representing indications for contrast-enhanced Magnetic Resonance Imaging (CE-MRI) are common also in a pediatric population. This study is a clinical routinely study in pediatric patients (male/ female) aged 2-17 years (3 age groups: 2-6, 7-11, and 12-17 years) who are scheduled to undergo Gd-enhanced MRI of brain, spine, liver and/or kidneys or Gd-enhanced MRA (single field of view). MedDRA version: 9.1
Conditions
Interventions
Trade Name: Gadovist®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: gadobutrol
CAS Number: 138071-82-6
Current Sponsor code: ZK 135079
Concentration unit: mmol/kg millimole(s)/kilo
Sponsors
Bayer Schering Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must fulfill the following inclusion criteria: 1.1.Patient is of specific age group, i.e. Age group I: 2 - 6 years Age group II: 7 - 11 years Age group III: 12 - 17 years 2. Patient is scheduled to undergo routine Gd-enhanced MRI of brain, spine, liver and/or kidneys or Gd-enhanced MRA (single field of view only) 3. Patient is able and willing to undergo the study MRI/MRA procedure with Gadovist 4. Patient is willing to comply with the study procedures (e.g. being followed-up for 24 (+/- 4) hours after the Gadovist injection) 5. Fully informed written consent of parent(s)/ legal representative(s) 6. Following informed consent by parent(s)/ legal representative(s), assent (as regarded as appropriate according to the opinion of the pediatrician and/or investigator) for active study participation is obtained based on age-appropriate trial information. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients are to be excluded from the study if they meet any of the following exclusion criteria: 1. Clinically unstable patient, e.g. patient in whom fluctuations in safety parameters may be observed during the study period due to underlying disease and/or respective treatment regiments (e.g. polytrauma patients, intensive care unit) 2. Patient undergoing a change in chemotherapy = 48 hours prior to and up to 24 hours after administration of Gadovist 3. Any planned intervention during the study and up to 24 hours after administration of Gadovist 4. Patient who has received or will receive any investigational drug 48 hours before MR-examination or during study participation. 5. Patient having received any other contrast agent within 30 hours prior to injection of Gadovist or likely to receive one during the 24-hour follow-up period 6. Patient presenting with contraindication for MRI, e.g. pacemaker, iron metal implants (e.g. aneurysm clips) or severe claustrophobia 7. Patient presenting with history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents 8. Severe inborn or acquired heart rhythm anomalies 9. Congenital long QT syndrome or family history of congenital long QT syndrome 10. Any medication that is known to prolong the QT interval 11. Uncorrected hypokalemia 12. Congenital heart defect or higher degree valvular pathology 13. Patient with renal insufficiency (i.e glomerular filtration rate (GFR) < 80% of age-adjusted normal value) 14. Patient with known and clinically relevant (e.g. more than 3 times upper limit of reference range) deviations of available clinical laboratory parameters from reference ranges, in particular with regard to liver / renal function and blood coagulation 15. Female adolescent who is pregnant or lactating 16. Female adolescent who is of childbearing potential and has not had a negative urine pregnancy test the same day as administration of Gadovist. The manufacturer’s instructions for performing the urinary pregnancy test are to be followed. 17. Previous participation in this study 18. Close affiliation with the investigational site; e.g. a close relative of the investigator 19. Child in institutionalized care (most vulnerable population) 20. Severely mentally or emotionally handicapped child according to the investigators opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: For the secondary pharmacokinetic objective, a quantitative evaluation of renally excreted gadolinium within a predefined collection period will be made up to 6 h post-injection in all patients aged > 9 years to evaluate the percentage of dose that is renally excreted within this time period. Evaluation of safety and tolerability of Gadovist 1.0 at the standard dose of 0.1 mmol/kg BW in children will be performed at baseline (within 24 hours pre-injection), immediately pre- and post-injection as well as during follow-up examinations up to 24 hours post-injection. In addition, MR images of Gadovist 1.0 at the standard dose of 0.1 mmol/kg BW will be assessed for contrast quality in children following MRI of brain/spine, liver and kidneys or MRA. ;Main Objective: The primary objective is to evaluate pharmacokinetic parameters of Gadovist 1.0 in plasma at the standard dose of 0.1 mmol/kg body weight in children of different age according to ICH E 11. To determine the pharmacokinetic parameters, blood samples need to be taken immediately prior to injection (baseline sample) as well as up to 8 hours post-injection. ;Primary end point(s): Pharmacokinetic (PK) parameters in plasma (primary PK variable): CL (Total clearance), AUC (Area under the drug concentration-time curve from administration to infinity), Vss (Volume of distribution at steady state), t1/2 (Terminal elimination half-life). | — |
Countries
Austria, Denmark, Germany, Sweden
Outcome results
None listed