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

NCT02411201 | Completed Phase 4 Results

• 2 other identifiers: DGD-44-0632013-003215-21
• Study Type: interventional
• Target: 51
• Locations: 4 countries
• Sites: 9

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.

Conditions

Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Simulated Plasma Concentration of DOTAREM

  at 10 and 20 min post-injection

• MRI Lesion Visualization at Subject Level

  Pre-injection and post-injection (estimated between 5 and 20 minutes after injection)

Study Arms (1)

DOTAREM

EXPERIMENTAL

Drug: DOTAREM

Interventions

DOTAREM DRUG

Single intravenous injection of 0.1 mmol/kg body weight

Also known as: gadoterate meglumine

DOTAREM

Eligibility Criteria

• Age: Up to 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Guerbet: lead

Study Sites (9)

Landes-Frauen-und Kinderklinik Linz

Linz, 4020, Austria

Location

CHU

Bordeaux, 33604, France

Location

CHRU

Lille, 59037, France

Location

Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Department of Molecular and Neurological Clinical and Research Center

Budapest, 1083, Hungary

Location

University of Debrecen Medical Center

Debrecen, 4032, Hungary

Location

Borsod-Abaúj-Zemplén University County Hospital

Miskolc, 3526, Hungary

Location

Uniwersytecki Szpital Dziecięcy w Lublinie

Lublin, 20093, Poland

Location

Instytut Pomnik -Centrum Zdrowia Dziecka

Warsaw, 04730, Poland

Location

MeSH Terms

Interventions

gadoterate meglumine

Results Point of Contact

• Title: Corinne Dubourdieu, PharmD, Head of Clinical Projects and Medical Writing
• Organization: Guerbet

corinne.dubourdieu@guerbet-group.com

+33 (0) 1 45 91 50 00

Study Officials

• Project Manager

  Guerbet

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: April 8, 2015
• Study Start: March 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 9, 2017
• Results First Posted: March 9, 2017

Record last verified: 2017-01

Locations

HU (3); AU (1); FR (3); PL (2)