E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029815 |
E.1.2 | Term | Nuclear magnetic resonance imaging |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | 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). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |