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Phase 1 N=44 Diagnostic

Gadobutrol Pharmacokinetic and Safety Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)

Magnetic Resonance Imaging

Enrolled (actual)
44
Serious AEs
6.8%
Results posted
Nov 2014
Primary outcome: Primary: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual — 776 micromole*h/L

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Gadobutrol (Gadavist, BAY86-4875) (Drug)
Age
Pediatric
Sex
All
Sponsor
Bayer
Primary completion
Nov 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
776
PRIMARY
Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual
0.128
PRIMARY
Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual
0.277
PRIMARY
Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual
2.18
PRIMARY
Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual
1.62
PRIMARY
Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)
339
PRIMARY
Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)
292
SECONDARY
Number of Subjects With Anatomical Area Evaluated
1; 1; 20; 20; 1; 1
SECONDARY
Number of Subjects With Technical Adequacy for Diagnosis
0; 0; 0; 0; 4; 3
SECONDARY
Number of Subjects With Technical Adequacy for Diagnosis by Body Region
1; 1; 1; 1; 20; 20
SECONDARY
Number of Subjects by Overall Contrast Quality
1; 0; 0; 5; 38
SECONDARY
Number of Subjects by Overall Contrast Quality by Body Region
1; 2; 19; 1; 1; 5
SECONDARY
Number of Subjects With Presence of Pathology
33; 33; 11; 11
SECONDARY
Number of Subjects With Presence of Pathology by Body Region
0; 0; 1; 1; 10; 10
SECONDARY
Number of Subjects With Number of Lesions Detected
2; 1; 29; 29; 2; 2
SECONDARY
Number of Subjects With Number of Lesions Detected by Body Region
1; 1; 10; 10; 1; 1
SECONDARY
Contrast Enhancement in Lesion or Vessel
44; 3; 0; 0; 0; 6
SECONDARY
Contrast Enhancement in Lesion or Vessel by Body Region
1; 1; 2; 0; 0; 2
SECONDARY
Number of Subjects With Border Delineation of Lesion of Vessel
5; 1; 6; 0; 9; 1
SECONDARY
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region
1; 1; 2; 2; 3; 0
SECONDARY
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement
6; 1; 11; 0; 27; 43
SECONDARY
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region
1; 1; 2; 2; 1; 0
SECONDARY
Number of Subjects With Diagnoses
1; 2; 4; 4; 1; 1
SECONDARY
Number of Subjects With Diagnoses by Body Region
1; 1; 1; 1; 1; 1
SECONDARY
Number of Subjects With Additional Diagnostic Gain
19; 24; 1
SECONDARY
Number of Subjects With Additional Diagnostic Gain by Body Region
1; 11; 9; 1; 2; 3
SECONDARY
Number of Subjects With Confidence in Diagnosis
6; 1; 14; 3; 24; 40
SECONDARY
Number of Subjects With Confidence in Diagnosis by Body Region
1; 1; 1; 0; 8; 0
SECONDARY
Number of Subjects With Final Diagnosis
24; 6; 6; 4; 2; 1
SECONDARY
Number of Subjects With Final Diagnosis by Body Region
1; 3; 1; 1; 6; 2
SECONDARY
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI
39; 5
SECONDARY
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region
1; 0; 20; 1; 2; 0
SECONDARY
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis
33; 11
SECONDARY
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region
1; 0; 17; 4; 1; 1
SECONDARY
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis
32; 12
SECONDARY
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region
1; 0; 16; 5; 1; 1
SECONDARY
Number of Subjects With Change in Management From Unenhanced to Combined MRI
36; 8
SECONDARY
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region
1; 0; 19; 2; 2; 0
SECONDARY
Number of Subjects With Clinically Significant Abnormal Laboratory Values
SECONDARY
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection
61.8; 91.7; 136.3; 115.2; 150.4

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01544166). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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