Magnetic Resonance ImagingPhase 1NCT01544166
Gadobutrol Pharmacokinetic and Safety Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)
A Phase 1 study testing Gadobutrol (Gadavist, BAY86-4875) in people with Magnetic Resonance Imaging, run by Bayer at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 2 years
- Conditions the study is for
- Magnetic Resonance Imaging
- What is being tested?
- Gadobutrol (Gadavist, BAY86-4875)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 16 May 2012to 28 Nov 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States5 sites
Study site
Boston, Massachusetts, 02111
Study site
Chicago, Illinois, 60611
Study site
Cincinnati, Ohio, 45229
Study site
Houston, Texas, 77030
Study site
Savannah, Georgia, 31406
Germany3 sites
Study site
Dresden, Saxony, 01307
Study site
Halle, Saxony-Anhalt, 06097
Study site
Jena, Thuringia, 07740
About this study
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
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.
Read more
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.
- Conditions
- Magnetic Resonance Imaging
- Being tested
- Gadobutrol (Gadavist, BAY86-4875)
- Keywords
- Gadolinium, Pediatrics, MRI, contrast
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gadobutrol (Gadavist, BAY86-4875)Drug
Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants <2 years of age.
| Study group | Role | What they receive |
|---|---|---|
| Overall study | Experimental | Not described Receives: Drug: Gadobutrol (Gadavist, BAY86-4875) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC from time 0 (start of injection) to infinity was reported in micromole*hour per liter (micromole*h/L).
Measured: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual
Clearance is the volume of the fluid presented to the eliminating organ that is effectively completely cleared of drug per unit time and depends on the rate of elimination. CL of gadobutrol normalized for body weight, was reported in Liter per hour per kilogram (L/(h*kg).
Measured: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual
Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state.
Measured: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual
MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.
Measured: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual
Half-life refers to the elimination of the drug, that is, the time it takes for the blood plasma concentration to reach half the concentration. Terminal elimination half-life of gadobutrol from plasma is expressed in hours and is derived from the terminal slope of the concentration versus time curve.
Measured: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C20 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
Measured: 20 minutes post-injection
Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C30 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
Measured: 30 minutes post-injection
Secondary outcomes (33)
Number of Subjects With Anatomical Area Evaluated
Subjects were referred for MRI of any body region. The primary anatomical area to be evaluated by MRI was assessed. Anatomical Area was recorded prior to gadobutrol injection for the unenhanced MRI procedure and after gadobutrol injection for the gadobutrol-enhanced MRI procedure. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Technical Adequacy for Diagnosis
The technical adequacy of the unenhanced image set and the combined unenhanced and enhanced image set was assessed based on the following 4 point scale: 1=Region visualized with artifacts compromising quality and interpretability of images, 2=Only partial evaluation of images possible, region not covered adequately anatomically, 3=Region visualized with artifacts, partially compromising image quality but evaluation and diagnosis still possible, 4=Region clearly visualized, excellent quality. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Technical Adequacy for Diagnosis by Body Region
The technical adequacy of the the unenhanced image set and the combined unenhanced and enhanced image set was assessed based 4-point scale and body region. Four-point scale: 1=Region visualized with artifacts compromising quality and interpretability of images, 2=Only partial evaluation of images possible, region not covered adequately anatomically, 3=Region visualized with artifacts, partially compromising image quality but evaluation and diagnosis still possible, 4=Region clearly visualized, excellent quality. Evaluation was done on pre-injection and combined images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Overall Contrast Quality
A qualitative assessment of the overall contrast using the following pre-defined 5-point scale: 1= None (for example, in case of a non-enhancing vessel), 2= Poor, 3= Moderate, 4= Good, 5= Excellent, was done. This parameter was assessed in the postcontrast MRI only, which is evaluated together with the unenhanced, this is why it is called combined. Data for combined MRI set was reported.
Measured: Images were taken post-injection (within about 15 minutes)
Number of Subjects by Overall Contrast Quality by Body Region
A qualitative assessment of the overall contrast using the following pre-defined 5-point scale: 1= None (for example, in case of a non-enhancing vessel), 2= Poor, 3= Moderate, 4= Good, 5= Excellent, was done in the postcontrast MRI only, which is evaluated together with the unenhanced, this is why it is called combined. Data for combined MRI set was reported.
Measured: Images were taken post-injection (within about 15 minutes)
Number of Subjects With Presence of Pathology
Presence of pathology was assessed for unenhanced and combined MRI sets and recorded as "yes/no". The number of lesions identified for each MRI set was recorded.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Presence of Pathology by Body Region
Presence of pathology was assessed for unenhanced and combined MRI sets and recorded as "yes/no". The number of lesions identified for each MRI set was recorded. Results per body region were reported.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Number of Lesions Detected
Presence of pathology included presence of lesions and was recorded as "yes/no". If "yes" the number of subjects with specified lists of lesions and body region was reported. Evaluation was done on pre- injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Number of Lesions Detected by Body Region
Presence of pathology included presence of lesions and was recorded as "yes/no". If "yes" the number of subjects with specified lists of lesions and body region was reported. Evaluation was done on pre- injection and combined (pre- and post-injection) images. Data of subjects with missing number of lesions or at least one lesion in unenhanced and combined MRI sets were reported.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Contrast Enhancement in Lesion or Vessel
The contrast-enhancement for each lesion or vessel was recorded on a 4-point scale: 1 = None, lesion or vessel is not enhanced; 2 = Moderate, lesion or vessel is weakly enhanced; 3 = Good, lesion or vessel is clearly enhanced; 4 = Excellent, lesion or vessel is clearly and brightly enhanced. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Contrast Enhancement in Lesion or Vessel by Body Region
The contrast-enhancement for each lesion or vessel was recorded on a 4-point scale: 1 = None, lesion or vessel is not enhanced; 2 = Moderate, lesion or vessel is weakly enhanced; 3 = Good, lesion or vessel is clearly enhanced; 4 = Excellent, lesion or vessel is clearly and brightly enhanced. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Border Delineation of Lesion of Vessel
The border delineation for each lesion or vessel was recorded on a 4-point scale: 1 = None, no or unclear delineation of the boundary between the lesion or vessel and the surrounding tissue; 2 = Moderate, some aspects of border delineation covered; 3 = Good, almost clear delineation, but not complete on relevant slices; 4 = Excellent, clear and complete delineation.Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region
The border delineation for each lesion or vessel was recorded on a 4-point scale: 1 = None, no or unclear delineation of the boundary between the lesion or vessel and the surrounding tissue; 2 = Moderate, some aspects of border delineation covered; 3 = Good, almost clear delineation, but not complete on relevant slices; 4 = Excellent, clear and complete delineation.The results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement
The degree of visualization of internal morphology and structure was recorded on a 3-point scale: 1= Poor, the structure and internal morphology of the lesion or vessel is poorly visible; 2 = Moderate, the structure and internal morphology of the lesion or vessel is visible but sufficient information cannot be obtained; 3 = Good, the structure and internal morphology of the lesion or vessel is sufficiently visible for diagnostic purposes.Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region
The degree of visualization of internal morphology and structure was recorded on a 3-point scale: 1 = Poor, the structure and internal morphology of the lesion or vessel is poorly visible; 2 = Moderate, the structure and internal morphology of the lesion or vessel is visible but sufficient information cannot be obtained; 3 = Good, the structure and internal morphology of the lesion or vessel is sufficiently visible for diagnostic purposes. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Diagnoses
The following diagnoses were reported for both the unenhanced MRI and the combined MRI image sets: Other diagnoses, No lesions/normal, Congenital disease/syndrome, Malignant lesion, Inflammation, Structural malformation, Benign lesion, and Vascular malformation. Evaluation was done on pre- injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Diagnoses by Body Region
The following diagnoses were reported for both the unenhanced MRI and the combined MRI image sets: Other diagnoses, No lesions/normal, Congenital disease/syndrome, Malignant lesion, Inflammation, Structural malformation, Benign lesion, and Vascular malformation. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Additional Diagnostic Gain
Additional diagnostic gain by the contrast-enhanced image set was assessed on a 3-point scale: scale 1 = Initial diagnosis unchanged, scale 2 = Initial diagnosis changed - improved, i.e. more specific, and scale 3 = Initial diagnosis changed -new diagnosis. Evaluation was done on combined (pre- and post- injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Additional Diagnostic Gain by Body Region
Additional diagnostic gain by the contrast-enhanced image set was assessed on a 3-point scale: scale 1 = Initial diagnosis unchanged, scale 2 = Initial diagnosis changed - improved, i.e. more specific, and scale 3 = Initial diagnosis changed -new diagnosis. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Confidence in Diagnosis
Diagnostic confidence based on the unenhanced MRI image sets and thereafter on the combined MRI image sets were assessed on a 3-point scale, as 1 = Not confident, 2 = Confident and 3 = Very confident. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Confidence in Diagnosis by Body Region
Diagnostic confidence based on the unenhanced MRI image sets and thereafter on the combined MRI image sets were assessed on a 3-point scale, as 3 = Very confident, 2 = Confident, and 1 = Not confident. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Final Diagnosis
The final diagnosis of the subjects was based on all clinical information available and was provided separately within 4 weeks after MRI. Evaluation was done on pre-injection and combined (pre- and post- injection) images.
Measured: Up to 4 weeks post-injection
Number of Subjects With Final Diagnosis by Body Region
The final diagnosis of the subjects was based on all clinical information available and was provided separately within 4 weeks after MRI. Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images. Only subjects with final diagnosis were reported.
Measured: Up to 4 weeks post-injection
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI
The analysis value for change in diagnosis was recorded as "yes/no". Evaluation was done on pre- injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region
The analysis value for change in diagnosis was recorded as "yes/no". Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis
The analysis value for change in diagnosis was recorded as "yes/no". Evaluation was done on pre- injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region
The analysis value for change in diagnosis was recorded as "yes/no". Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis
The analysis value for change in diagnosis was recorded as "yes/no". Evaluation was done on pre- injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region
The analysis value for change in diagnosis was recorded as "yes/no". Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Management From Unenhanced to Combined MRI
The subject management was indicated based on the unenhanced images alone. The analysis value for change in subject management was recorded as "yes/no". Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region
The subject management was indicated based on the unenhanced images alone. The analysis value for change in subject management was recorded as "yes/no". Results per body regions were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
Measured: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Clinically Significant Abnormal Laboratory Values
Change in post-injection test values, such as resulting in a change in subject management or which were not the result of laboratory error and were considered clinically significant by the investigator was reported.
Measured: Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection
eGFR was calculated based on the Schwartz formula with blood sampling for serum creatinine (Scr) not exceeding 14 days prior to gadobutrol injection. Otherwise, the eGFR was obtained from the original Schwartz formula: eGFR = k * height / Scr where k = 0.45 in term newborn infants < 1 year of age, and k = 0.55 in children up to 13 years of age. If Scr was measured by an enzymatic creatinine method that had been calibrated to be traceable to Isotope dilution mass spectroscopy (IDMS), the updated Schwartz formula was used: eGFR = 0.413*height/Scr.
Measured: Before gadobutrol injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2012 (estimated)
- Study start16 May 2012
- Primary completion28 Nov 2013
- Study completion28 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Magnetic Resonance ImagingStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01544166
- Sponsor's protocol ID
- 91741
- Other IDs
- 2010-023003-96
- Status last verified
- Nov 2020
- First submitted
- 28 Feb 2012
- Last updated
- 16 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01544166
- Acronym / sponsor ID
- 91741
- Conditions
- Magnetic Resonance Imaging
- Keywords
- Gadolinium, Pediatrics, MRI, contrast
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 16 May 2012 (actual)
- Primary completion
- 28 Nov 2013 (actual)
- Study completion
- 28 Nov 2013 (actual)
- First posted
- 5 Mar 2012 (estimated)
- Results
- Posted 26 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Overall study | Experimental | Drug: Gadobutrol (Gadavist, BAY86-4875) |
Who may qualify
- Ages
- Up to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gadobutrol (Gadavist, BAY86-4875)Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants <2 years of age. | Drug | Overall study |
Primary outcome
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
Time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC from time 0 (start of injection) to infinity was reported in micromole*hour per liter (micromole*h/L).
Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual
Time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Clearance is the volume of the fluid presented to the eliminating organ that is effectively completely cleared of drug per unit time and depends on the rate of elimination. CL of gadobutrol normalized for body weight, was reported in Liter per hour per kilogram (L/(h*kg).
Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual
Time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state.
Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual
Time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.
Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual
Time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Half-life refers to the elimination of the drug, that is, the time it takes for the blood plasma concentration to reach half the concentration. Terminal elimination half-life of gadobutrol from plasma is expressed in hours and is derived from the terminal slope of the concentration versus time curve.
Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)
Time frame: 20 minutes post-injection
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C20 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)
Time frame: 30 minutes post-injection
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C30 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
33 secondary outcomes
Number of Subjects With Anatomical Area Evaluated
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Technical Adequacy for Diagnosis
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Technical Adequacy for Diagnosis by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Overall Contrast Quality
Time frame: Images were taken post-injection (within about 15 minutes)
Number of Subjects by Overall Contrast Quality by Body Region
Time frame: Images were taken post-injection (within about 15 minutes)
Number of Subjects With Presence of Pathology
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Presence of Pathology by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Number of Lesions Detected
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Number of Lesions Detected by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Contrast Enhancement in Lesion or Vessel
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Contrast Enhancement in Lesion or Vessel by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Border Delineation of Lesion of Vessel
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Diagnoses
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Diagnoses by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Additional Diagnostic Gain
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Additional Diagnostic Gain by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Confidence in Diagnosis
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Confidence in Diagnosis by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Final Diagnosis
Time frame: Up to 4 weeks post-injection
Number of Subjects With Final Diagnosis by Body Region
Time frame: Up to 4 weeks post-injection
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Management From Unenhanced to Combined MRI
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region
Time frame: Images were taken pre-injection and post-injection (within about 15 minutes)
Number of Subjects With Clinically Significant Abnormal Laboratory Values
Time frame: Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection
Time frame: Before gadobutrol injection
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gadobutrol (Gadavist, BAY86-4875) in people with Magnetic Resonance Imaging, run by Bayer at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Germany, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual (time frame: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.