Pediatric subject aged <2 years (term newborn infants to toddlers 23 months of age inclusive) scheduled to undergo routine gadolinium-enhanced Magnetic Resonance Imaging of any body region MedDRA version: 16.1 Level: PT Classification code 10058644 Term: Nuclear magnetic resonance imaging whole body System Organ Class: 10022891 - Investigations
Conditions
Interventions
Trade Name: Dotarem 0.5 mmol/ml
Product Name: Dotarem 0.5 mmol/ml, solution for injection in vials
Product Code: G449.06
Pharmaceutical Form: Solution for injection
Sponsors
GUERBET
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Pediatric subject aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Subject planned for intervention (e.g. surgery) between the screening visit and up to 24 hours after DOTAREM injection •Subject whose preceding or subsequent treatment to DOTAREM injection (e.g., blood loss or receiving blood, treatment with diuretics, etc…) would alter DOTAREM pharmacokinetics parameters •Subject with subsequent planned treatment after DOTAREM injection that would prevent obtaining the required blood samples (e.g., emergency surgery, etc…) •Subject with a history of a bleeding disorder •Subject with severe liver disease (Child’s Pugh Classification B or greater or serum direct bilirubin greater than 0.3 mg/dL, age adjusted) •Subject with electrolyte or fluid imbalance that presents undue risk •Subject undergoing a change in chemotherapy within 48 hours prior to and up to 24 hours after DOTAREM injection •Subject who received or will receive any other contrast agent within 72 hours prior to DOTAREM injection or up to 24 hours after DOTAREM injection •Subject with contraindication for MRI such as iron metal implants (e.g. aneurysm clips) •Subject with history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents •Subject having participated within 30 days in a clinical study involving an investigational drug or device •Subject planned to participate simultaneously to another clinical study •Any condition which, based on the investigator's clinical judgement, would prevent the subject from participating in all study assessments and visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate pharmacokinetics profile in plasma of DOTAREM following single intravenous injection in pediatric subjects aged up to 23 months (inclusive);Secondary Objective: -To evaluate the DOTAREM safety (clinical and biological) following single administration up to 7 ± 1 day. -To evaluate efficacy of DOTAREM-enhanced MRI in brain (intracranial), spine and associated tissues in a subgroup of at least 20 subjects as assessed by on-site investigator;Primary end point(s): DOTAREM pharmacokinetics in plasma: •The start of administration is set as time point 0 (T0), and blood samples will be collected during three time windows as 10 to 60 min, 2.0 to 4.0 hours and 6.0 to 8.0 hours post-injection, at time points which are allocated by randomization. •DOTAREM concentrations in plasma will be analyzed using a validated LC-MS-MS method. •The following pharmacokinetic parameters from plasma samples will be determined from typical and individual DOTAREM concentration-time profiles: AUC, ß, t½ß, ClT, Vd.;Timepoint(s) of evaluation of this end point: The start of administration is set as time point 0 (T0), and blood samples will be collected during three time windows as 10 to 60 min, 2.0 to 4.0 hours and 6.0 to 8.0 hours post-injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical and biological safety: •Height and weight at screening visit •Vital signs (blood pressure and heart rate) at several time points/intervals (at baseline (prior to injection), post injection immediately after MRI, between 2 and 4 hours and at 24 ± 4 hours) •Blood samples for safety laboratory variables centrally analyzed (biochemistry and hematology) at screening and post injection at 24 ± 4 hours •Estimated glomerular filtration rate (eGFR) at screening and post injection at 24 ± 4 hours •Urine samples for safety assessment (urinalysis with dipstick) at screening and post injection at 24 ± 4 hours •Tolerance at the injection site over 24 ± 4 hours after injection. •Adverse events will be monitored from the beginning of subject’s participation in the study (ICF signature) to the end of a 7 ± 1 day follow-up period. DOTAREM-MRI efficacy evaluation in brain (intracranial), spine and associated tissues (pre and post contrast assessment): •Lesion visualization: lesions will be assessed by on-site radiologist using a 3-point scale for 3 co-endpoints (lesion border delineation, internal morphology and contrast enhancement). •Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR) and Pre-Post Contrast Variation (?CNR) will be computed. •Quality of T1 weighted images will be assessed using a 3 graded scale.;Timepoint(s) of evaluation of this end point: •Height and weight at screening visit •Vital signs at baseline (prior to injection), post injection immediately after MRI, between 2 and 4 hours and at 24 ± 4 hours •Blood samples for safety laboratory variables centrally a nalyzed at screening and post injection at 24 ± 4 hours •Estimated glomerular filtration rate (eGFR) at screening and post injection at 24 ± 4 hours •Urine samples for safety assessment (urinalysis with dipstick) at screening and post injection at 24 ± 4 hours •Tolerance at the injection site over 24 ± 4 hours after injection. •Adverse eve | — |
Countries
Austria, France, Hungary
Contacts
Public ContactClinical Development
GUERBET
Outcome results
None listed