DOTAREM Pharmacokinetics and Safety Study in Pediatric Subjects Aged < 2 Years

DOTAREM® Pharmacokinetics, Safety and Efficacy Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)

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.

Study Overview

• Status: Completed
• Conditions: Magnetic Resonance Imaging
• Intervention / Treatment: Drug: DOTAREM

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4020
    • Landes-Frauen-und Kinderklinik Linz
• France
  • Bordeaux, France, 33604
    • CHU
  • Lille, France, 59037
    • CHRU
  • Strasbourg, France, 67098
    • Hôpital de Hautepierre
• Hungary
  • Budapest, Hungary, 1083
    • Department of Molecular and Neurological Clinical and Research Center
  • Debrecen, Hungary, 4032
    • University of Debrecen Medical Center
  • Miskolc, Hungary, 3526
    • Borsod-Abaúj-Zemplén University County Hospital
• Poland
  • Lublin, Poland, 20093
    • Uniwersytecki Szpital Dziecięcy w Lublinie
  • Warszawa, Poland, 04730
    • Instytut Pomnik -Centrum Zdrowia Dziecka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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, estimated glomerular filtration rate calculated based on the Schwartz formula

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DOTAREM	Drug: DOTAREM; Single intravenous injection of 0.1 mmol/kg body weight; Other Names: gadoterate meglumine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of DOTAREM in Plasma	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.	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
Rate Constant of the Terminal Phase of DOTAREM	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.	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
Terminal Elimination Half-life of DOTAREM From Plasma	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.	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
Total Clearance of DOTAREM From Plasma	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.	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
Volume of Distribution of DOTAREM at Steady State	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simulated Plasma Concentration of DOTAREM	Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method.	at 10 and 20 min post-injection
MRI Lesion Visualization at Subject Level	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)	Pre-injection and post-injection (estimated between 5 and 20 minutes after injection)

Collaborators and Investigators

• Sponsor: Guerbet
• Investigators: Study Director: Project Manager, Guerbet

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: March 11, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (ESTIMATE): April 8, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
• Other Study ID Numbers: DGD-44-063; 2013-003215-21 (EUDRACT_NUMBER)