DOTAREM Pharmacokinetics and Safety Study in Pediatric Subjects Aged < 2 Years
- Registration Number
- NCT02411201
- Lead Sponsor
- Guerbet
- Brief Summary
The main purpose of the study is to evaluate the pharmacokinetics of DOTAREM® in the body of children aged less than 2 years thanks to several blood samples (3 ml in total) taken following the administration of DOTAREM®.
DOTAREM® is a contrast agent commonly used for enhancement of Magnetic Resonance Imaging (MRI) to potentially improve the quality of the images and help the diagnosis. Children aged less than 2 years scheduled to undergo routine gadolinium-enhanced MRI of any body region may take part in the study. In this case they will receive DOTAREM®, a solution injected at the standard dose of 0.2mL/kg (0.1 mmol/kg) of body weight.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 51
- 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, estimated glomerular filtration rate calculated based on the Schwartz formula
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DOTAREM DOTAREM -
- Primary Outcome Measures
Name Time Method Rate Constant of the Terminal Phase of DOTAREM Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Rate constant of the terminal phase was determined from typical and individual DOTAREM concentration-time profiles.
Total Clearance of DOTAREM From Plasma Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Total clearance was determined from typical and individual DOTAREM concentration-time profiles.
Area Under the Curve of DOTAREM in Plasma Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Area under the curve was determined from typical and individual DOTAREM concentration-time profiles.
Terminal Elimination Half-life of DOTAREM From Plasma Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Terminal elimination half-life was determined from typical and individual DOTAREM concentration-time profiles.
Volume of Distribution of DOTAREM at Steady State Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Volume of distribution at steady state was determined from typical and individual DOTAREM concentration-time profiles.
- Secondary Outcome Measures
Name Time Method Simulated Plasma Concentration of DOTAREM at 10 and 20 min post-injection Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method.
MRI Lesion Visualization at Subject Level Pre-injection and post-injection (estimated between 5 and 20 minutes after injection) Lesion visualization was assessed on up to five most representative lesions per subject based on scoring of 3 co-endpoints:
* border delineation (based on a 3-point scale where 1=none; 2=moderate and 3=clear and complete)
* internal morphology (based on a 3-point scale where 1=poorly visible; 2=moderately visible and 3=sufficiently visible)
* contrast enhancement (based on a 3-point scale where 1=none; 2=weak and 3=clear and bright)
For each co-endpoint, a sum of scores was calculated at subject level as follows: sum of scores = score of the lesion 1 (+ score of the lesion 2 + score of the lesion 3 + score of the lesion 4 + score of the lesion 5, when applicable)
Trial Locations
- Locations (9)
CHU
🇫🇷Bordeaux, France
Uniwersytecki Szpital Dziecięcy w Lublinie
🇵🇱Lublin, Poland
Hôpital de Hautepierre
🇫🇷Strasbourg, France
CHRU
🇫🇷Lille, France
Department of Molecular and Neurological Clinical and Research Center
🇭🇺Budapest, Hungary
Borsod-Abaúj-Zemplén University County Hospital
🇭🇺Miskolc, Hungary
Landes-Frauen-und Kinderklinik Linz
🇦🇹Linz, Austria
University of Debrecen Medical Center
🇭🇺Debrecen, Hungary
Instytut Pomnik -Centrum Zdrowia Dziecka
🇵🇱Warszawa, Poland