Clinical trial NCT01544166: Gadobutrol Pharmacokinetic and Safety Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)
Official title: Open-label, Multicenter, Pharmacokinetic, and Safety Study in Children (Term Newborn Infants to 23 Months of Age) Undergoing a Contrast-enhanced MRI With an Intravenous Injection of 0.1 mmol/kg BW Gadobutrol 1.0 M
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Magnetic Resonance Imaging
Keywords: Gadolinium, Pediatrics, MRI, contrast
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 44
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The main purpose of this study is to collect data on the way gadobutrol is taken into, moves around, and is eliminated from, the body of children aged 0 to less than 2 years. The study will also evaluate safety and tolerability, and efficacy of gadobutrol.

A maximum total amount of approximately 5 ml of blood will be needed for these analyses which will be drawn within 2-3 days.

Gadobutrol is a contrast agent used for enhancement of Magnetic Resonance Imaging (MRI), potentially allowing better visibility of tissues in the body. Children aged under 2 years scheduled for a routine contrast-enhanced MRI examination of any body region may take part in this study, in which case they will receive gadobutrol as contrast agent intravenously at the standard dose of 0.1 mmol/kg (0.1 ml/Kg) of body weight. Only subjects without renal insufficiency of any intensity (i.e. estimated Glomerular Filtration Rate \<80% of age adjusted normal value calculated based on the Schwartz formula) will be included in the trial.

The duration of this study as a whole is around 1 year and the total number of children to be enrolled is 50. A child will be expected to take part in the study for around 7 days.


Eligibility criteria: Inclusion Criteria:

* Pediatric subjects aged \<2 years (term newborn infants to toddlers 23 months of age inclusive)
* Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region

Exclusion Criteria:

* Subjects undergoing a change in chemotherapy within 48 hours prior to and up to 24 hours after gadobutrol injection
* Any planned intervention during the study and up to 24 hours after gadobutrol injection (excluding lumbar puncture)
* Subjects who received or will receive any investigational product within 48 hours before gadobutrol injection or during study participation
* Subjects who received or will receive any other contrast agent within 48 hours prior to gadobutrol injection or up to 24 hours after gadobutrol injection
* Subjects with contraindication for MRI such as iron metal implants (e.g. aneurysm clips)
* History of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents
* Subject with renal insufficiency of any intensity, i.e. estimated Glomerular Filtration Rate \<80% of age adjusted normal value calculated based on the Schwartz formula

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
timeFrame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
measure: Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual
timeFrame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
measure: Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual
timeFrame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
measure: Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual
timeFrame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
measure: Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual
timeFrame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
measure: Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)
timeFrame: 20 minutes post-injection
measure: Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)
timeFrame: 30 minutes post-injection
Secondary outcomes:
measure: Number of Subjects With Anatomical Area Evaluated
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Technical Adequacy for Diagnosis
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Technical Adequacy for Diagnosis by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects by Overall Contrast Quality
timeFrame: Images were taken post-injection (within about 15 minutes)
measure: Number of Subjects by Overall Contrast Quality by Body Region
timeFrame: Images were taken post-injection (within about 15 minutes)
measure: Number of Subjects With Presence of Pathology
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Presence of Pathology by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Number of Lesions Detected
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Number of Lesions Detected by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Contrast Enhancement in Lesion or Vessel
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Contrast Enhancement in Lesion or Vessel by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Border Delineation of Lesion of Vessel
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Border Delineation of Lesion of Vessel by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Diagnoses
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Diagnoses by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Additional Diagnostic Gain
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Additional Diagnostic Gain by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Confidence in Diagnosis
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Confidence in Diagnosis by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Final Diagnosis
timeFrame: Up to 4 weeks post-injection
measure: Number of Subjects With Final Diagnosis by Body Region
timeFrame: Up to 4 weeks post-injection
measure: Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Management From Unenhanced to Combined MRI
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region
timeFrame: Images were taken pre-injection and post-injection (within about 15 minutes)
measure: Number of Subjects With Clinically Significant Abnormal Laboratory Values
timeFrame: Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection
measure: Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection
timeFrame: Before gadobutrol injection
Other outcomes:
measure: Number of Subjects With Drug Related Serious and Non- Serious Adverse Events
timeFrame: From baseline to approximately 7 days after injection
Locations:
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Cincinnati
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Edmonton
country: Canada
state: Alberta
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Dresden
country: Germany
state: Sachsen
city: Jena
country: Germany
state: Thüringen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: