Study to evaluate the product flow, breakdown and elimination of DOTAREM from the blood and its safety and efficacy in children aged > 2 years

• Register: EUCTR
• Last refreshed on: 25 January 2016
• Main ID: EUCTR2013-003215-21-HU
• Date of registration: 09/07/2014
• Prospective Registration: Yes
• Primary sponsor: GUERBET
• Public title: Study to evaluate the product flow, breakdown and elimination of DOTAREM from the blood and its safety and efficacy in children aged > 2 years
• Scientific title: DOTAREM® Pharmacokinetics, Safety and Efficacy Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)
• Date of first enrolment: 21/11/2014
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003215-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Hungary

Contacts

• Name: Clinical Development
• Affiliation: GUERBET

• Name: Clinical Development
• Affiliation: GUERBET

Key inclusion & exclusion criteria

Inclusion criteria:
•Pediatric subject aged <2 years (term newborn infants to toddlers 23 months of age inclusive). Term is defined as =37 weeks of amenorrhea
•Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region (e.g. CNS, cardiac) at the dose of 0.1 mmol/kg BW (0.2 mL/kg BW)
•Subject with normal renal function for its age, - according to estimated glomerular filtration rate calculated based on the Schwartz formula
•Subject whose parents or legal guardian (where applicable) has/have provided his/her/their fully informed written consent for the participation of the child in the trial. Parents or guardian must have the ability to read, understand and willingness to sign the informed consent form
•Subject with health insurance, according to the local regulatory requirement
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
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:
•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 known severe liver disease
•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 who received will receive any investigational product within 7 days before DOTAREM injection or during study participation
•Any condition which, based on the investigator's clinical judgement, would prevent the subject from participating in all study assessments and visits


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

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: 18.0 Level: PT Classification code 10058644 Term: Nuclear magnetic resonance imaging whole body System Organ Class: 10022891 - Investigations

Intervention(s)

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
INN or Proposed INN: GADOTERIC ACID
CAS Number: 72573-82-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 279.32-

Primary Outcome(s)

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.

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

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

Main Objective: To evaluate pharmacokinetics profile in plasma of DOTAREM following single intravenous injection in pediatric subjects aged up to 23 months (inclusive)

Secondary Outcome(s)

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) centrally analyzed 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) centrally analyzed 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 from the beginning of subject’s participation in the study (ICF signature) to the end of a 7 ± 1 day follow-up period.
•MRI efficacy (pre and post contrast assessment) evaluated at D0

Secondary ID(s)

65.041

DGD-44-063

Source(s) of Monetary Support

GUERBET