Trial Outcomes & Findings for Gadobutrol Pharmacokinetic and Safety Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive) (NCT NCT01544166)

NCT ID: NCT01544166

Last Updated: 2020-12-16

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 44 participants
• Primary outcome timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
• Results posted on: 2020-12-16

Participant Flow

Pediatric subjects who were less than (<) 2 years of age, scheduled to undergo contrast-enhanced magnetic resonance imaging (MRI) for routine diagnostic purposes were included in the study and were recruited from 9 centres in Canada, Germany and United States of America.

Total of 47 subjects were screened worldwide in the study and 44 were enrolled (i.e. assigned to study drug). It included 3 screening failures (3 patients were not treated and did not complete the study).

Participant milestones

Measure	Overall Study Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.
Overall Study STARTED	44
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.
Age, Continuous	8.8 months STANDARD_DEVIATION 7.1 • n=5 Participants
Age, Customized Newborns (0-27 days)	5 Participants n=5 Participants
Age, Customized Infants and toddlers (28 days-23 months)	39 Participants n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

Population: Per-protocol set (PPS) included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample.

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).

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual	776 micromole*h/L Interval 544.0 to 1470.0	—

PRIMARY outcome

Timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample.

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).

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual	0.128 L/(h*kg) Interval 0.0666 to 0.184	—

PRIMARY outcome

Timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample.

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.

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual	0.277 L/kg Interval 0.236 to 0.409	—

PRIMARY outcome

Timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample.

MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual	2.18 hours Interval 1.57 to 4.68	—

PRIMARY outcome

Timeframe: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample.

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.

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual	1.62 hours Interval 1.16 to 3.37	—

PRIMARY outcome

Timeframe: 20 minutes post-injection

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample. Here number of subjects analysed= 43. C20 was simulated for 2400 virtual paediatric participants.

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.

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)	339 micromole/L Interval 230.0 to 456.0	—

PRIMARY outcome

Timeframe: 30 minutes post-injection

Population: PPS included those subjects who received the appropriate dose of gadobutrol based on the dose specification of 0.1 mmol/kg BW plus/minus 10% and had quantifiable gadolinium plasma concentrations in at least 1 valid PK sample. C30 was simulated for 2400 virtual paediatric participants.

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.

Outcome measures

Measure	Overall Study n=43 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)	292 micromole/L Interval 194.0 to 394.0	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Anatomical Area Evaluated Pelvic area:Trochanter major, femur neck	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Abdomen: Liver	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Brain: Brain	20 subjects	20 subjects
Number of Subjects With Anatomical Area Evaluated Brain: Orbit and brain	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Chest/thorax: Lung	2 subjects	2 subjects
Number of Subjects With Anatomical Area Evaluated Head/neck: Head	3 subjects	3 subjects
Number of Subjects With Anatomical Area Evaluated Head/neck: Neck	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Head/neck: Skull base/mandible	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Lymphatic system: Right arm	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Pelvic area: Testis	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Retroperitoneal: Kidney	6 subjects	6 subjects
Number of Subjects With Anatomical Area Evaluated Retroperitoneal: Adrenal gland	1 subjects	1 subjects
Number of Subjects With Anatomical Area Evaluated Spine: Spinal cord	4 subjects	4 subjects
Number of Subjects With Anatomical Area Evaluated Spine: Lumbar spine	1 subjects	1 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Technical Adequacy for Diagnosis Score = 1	0 subjects	0 subjects
Number of Subjects With Technical Adequacy for Diagnosis Score = 2	0 subjects	0 subjects
Number of Subjects With Technical Adequacy for Diagnosis Score = 3	4 subjects	3 subjects
Number of Subjects With Technical Adequacy for Diagnosis Score = 4	40 subjects	41 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Head/neck: Score 4	4 subjects	4 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Abdomen: Score 4	1 subjects	1 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Brain: Score 3	1 subjects	1 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Brain: Score 4	20 subjects	20 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Chest/thorax: Score 4	2 subjects	2 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Head/neck: Score 3	1 subjects	1 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Lymphatic system: Score 4	1 subjects	1 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Pelvic area: Score 4	2 subjects	2 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Retroperitoneal area: Score 4	7 subjects	7 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Spine: Score 3	2 subjects	1 subjects
Number of Subjects With Technical Adequacy for Diagnosis by Body Region Spine: Score 4	3 subjects	4 subjects

SECONDARY outcome

Timeframe: Images were taken post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects by Overall Contrast Quality None	1 subjects	—
Number of Subjects by Overall Contrast Quality Poor	0 subjects	—
Number of Subjects by Overall Contrast Quality Moderate	0 subjects	—
Number of Subjects by Overall Contrast Quality Good	5 subjects	—
Number of Subjects by Overall Contrast Quality Excellent	38 subjects	—

SECONDARY outcome

Timeframe: Images were taken post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects by Overall Contrast Quality by Body Region Abdomen: Excellent	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Brain: Good	2 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Brain: Excellent	19 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Chest/Thorax: Good	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Chest/Thorax: Excellent	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Head/Neck: Excellent	5 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Lymphatic system: Excellent	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Pelvic area: Excellent	2 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Retroperitoneal: None	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Retroperitoneal: Good	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Retroperitoneal: Excellent	5 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Spine: Good	1 subjects	—
Number of Subjects by Overall Contrast Quality by Body Region Spine: Excellent	4 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Presence of Pathology Yes	33 subjects	33 subjects
Number of Subjects With Presence of Pathology No	11 subjects	11 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Presence of Pathology by Body Region Abdomen: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Abdomen: Yes	1 subjects	1 subjects
Number of Subjects With Presence of Pathology by Body Region Brain: No	10 subjects	10 subjects
Number of Subjects With Presence of Pathology by Body Region Brain: Yes	11 subjects	11 subjects
Number of Subjects With Presence of Pathology by Body Region Chest/Thorax: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Chest/Thorax: Yes	2 subjects	2 subjects
Number of Subjects With Presence of Pathology by Body Region Head/Neck: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Head/Neck: Yes	5 subjects	5 subjects
Number of Subjects With Presence of Pathology by Body Region Lymphatic system: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Lymphatic system: Yes	1 subjects	1 subjects
Number of Subjects With Presence of Pathology by Body Region Pelvic area: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Pelvic area: Yes	2 subjects	2 subjects
Number of Subjects With Presence of Pathology by Body Region Retroperitoneal: No	0 subjects	0 subjects
Number of Subjects With Presence of Pathology by Body Region Retroperitoneal: Yes	7 subjects	7 subjects
Number of Subjects With Presence of Pathology by Body Region Spine: No	1 subjects	1 subjects
Number of Subjects With Presence of Pathology by Body Region Spine: Yes	4 subjects	4 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation. 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Number of Lesions Detected Number of lesions=missing	2 subjects	1 subjects
Number of Subjects With Number of Lesions Detected Number of lesions=1	29 subjects	29 subjects
Number of Subjects With Number of Lesions Detected Number of lesions=2	2 subjects	2 subjects
Number of Subjects With Number of Lesions Detected Number of lesions=10	0 subjects	1 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation. 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Number of Lesions Detected by Body Region Abdomen: Missing lesion	1 subjects	1 subjects
Number of Subjects With Number of Lesions Detected by Body Region Brain: 1 lesion	10 subjects	10 subjects
Number of Subjects With Number of Lesions Detected by Body Region Brain: 2 lesion	1 subjects	1 subjects
Number of Subjects With Number of Lesions Detected by Body Region Chest/Thorax: 1 lesion	2 subjects	2 subjects
Number of Subjects With Number of Lesions Detected by Body Region Head/Neck: Missing lesion	1 subjects	0 subjects
Number of Subjects With Number of Lesions Detected by Body Region Head/Neck: 1 lesion	4 subjects	4 subjects
Number of Subjects With Number of Lesions Detected by Body Region Head/Neck: 10 lesion	0 subjects	1 subjects
Number of Subjects With Number of Lesions Detected by Body Region Lymphatic system: 1 lesion	1 subjects	1 subjects
Number of Subjects With Number of Lesions Detected by Body Region Pelvic area: 1 lesion	2 subjects	2 subjects
Number of Subjects With Number of Lesions Detected by Body Region Retroperitoneal: 1 lesion	6 subjects	6 subjects
Number of Subjects With Number of Lesions Detected by Body Region Retroperitoneal: 2 lesion	1 subjects	1 subjects
Number of Subjects With Number of Lesions Detected by Body Region Spine: 1 lesion	4 subjects	4 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Contrast Enhancement in Lesion or Vessel None	44 subjects	3 subjects
Contrast Enhancement in Lesion or Vessel Moderate	0 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel Good	0 subjects	6 subjects
Contrast Enhancement in Lesion or Vessel Excellent	0 subjects	35 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Contrast Enhancement in Lesion or Vessel by Body Region Abdomen: None	1 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Blood vessel: None	2 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Blood vessel: Excellent	0 subjects	2 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Brain: None	19 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Brain: Good	0 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Brain: Excellent	0 subjects	18 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Chest/Thorax: None	2 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Chest/Thorax: Good	0 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Head/Neck: None	5 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Head/Neck: Good	0 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Head/Neck: Excellent	0 subjects	4 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Lymphatic system: None	1 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Lymphatic system: Excellent	0 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Pelvic area: None	2 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Pelvic area: Good	0 subjects	2 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Retroperitoneal: None	7 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Retroperitoneal: Excellent	0 subjects	6 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Spine: None	5 subjects	0 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Spine: Good	0 subjects	1 subjects
Contrast Enhancement in Lesion or Vessel by Body Region Spine: Excellent	0 subjects	4 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Border Delineation of Lesion of Vessel None	5 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel Moderate	6 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel Good	9 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel Excellent	24 subjects	42 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Spine: None	2 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Spine: Moderate	2 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Spine: Excellent	1 subjects	5 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Head/Neck: Good	2 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Head/Neck: Excellent	3 subjects	4 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Brain: Moderate	3 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Abdomen: Excellent	1 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Blood vessel: Excellent	2 subjects	2 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Brain: Good	6 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Brain: Excellent	10 subjects	19 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Chest/Thorax: Good	1 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Chest/Thorax: Excellent	1 subjects	2 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Lymphatic system: Excellent	1 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Pelvic area: Moderate	1 subjects	0 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Pelvic area: Excellent	1 subjects	2 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Retroperitoneal: None	3 subjects	1 subjects
Number of Subjects With Border Delineation of Lesion of Vessel by Body Region Retroperitoneal: Excellent	4 subjects	6 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement Poor	6 subjects	1 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement Moderate	11 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement Good	27 subjects	43 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Abdomen: Good	1 subjects	1 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Blood vessel: Good	2 subjects	2 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Brain: Poor	1 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Brain: Moderate	5 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Brain: Good	13 subjects	19 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Chest/Thorax: Moderate	1 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Chest/Thorax: Good	1 subjects	2 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Head/Neck: Poor	1 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Head/Neck: Good	4 subjects	5 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Lymphatic system: Good	1 subjects	1 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Pelvic area: Moderate	2 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Pelvic area: Good	0 subjects	2 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Retroperitoneal: Poor	3 subjects	1 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Retroperitoneal: Good	4 subjects	6 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Spine: Poor	1 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Spine: Moderate	3 subjects	0 subjects
Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region Spine: Good	1 subjects	5 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Diagnoses Benign lesion	1 subjects	2 subjects
Number of Subjects With Diagnoses Malignant lesion	4 subjects	4 subjects
Number of Subjects With Diagnoses Vascular malformation	1 subjects	1 subjects
Number of Subjects With Diagnoses Structural malformation	2 subjects	2 subjects
Number of Subjects With Diagnoses Inflammation	2 subjects	3 subjects
Number of Subjects With Diagnoses Congenital disease / syndrome	6 subjects	8 subjects
Number of Subjects With Diagnoses No lesion/Normal	10 subjects	11 subjects
Number of Subjects With Diagnoses Other	18 subjects	13 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Diagnoses by Body Region Abdomen: Other	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Brain: Malignant lesion	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Brain: Inflammation	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Brain: Congenital disease/syndrome	3 subjects	3 subjects
Number of Subjects With Diagnoses by Body Region Brain: No lesion/Normal	9 subjects	10 subjects
Number of Subjects With Diagnoses by Body Region Brain: Other	7 subjects	6 subjects
Number of Subjects With Diagnoses by Body Region Chest/Thorax: Structural malformation	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Chest/Thorax: Other	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Head/Neck: Benign lesion	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Head/Neck: Malignant lesion	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Head/Neck: Inflammation	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Head/Neck: Other	2 subjects	2 subjects
Number of Subjects With Diagnoses by Body Region Lymphatic system: Vascular malformation	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Pelvic area: Benign lesion	0 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Pelvic area: Inflammation	0 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Pelvic area: Other	2 subjects	0 subjects
Number of Subjects With Diagnoses by Body Region Retroperitoneal: Malignant lesion	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Retroperitoneal: Congenital disease/syndrome	3 subjects	5 subjects
Number of Subjects With Diagnoses by Body Region Retroperitoneal: Other	3 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Spine: Malignant lesion	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Spine: Structural malformation	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Spine: No lesion/Normal	1 subjects	1 subjects
Number of Subjects With Diagnoses by Body Region Spine: Other	2 subjects	2 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Additional Diagnostic Gain Scale 1	19 subjects	—
Number of Subjects With Additional Diagnostic Gain Scale 2	24 subjects	—
Number of Subjects With Additional Diagnostic Gain Scale 3	1 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Additional Diagnostic Gain by Body Region Abdomen: Scale 2	1 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Brain: Scale 1	11 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Brain: Scale 2	9 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Brain: Scale 3	1 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Chest/Thorax: Scale 2	2 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Head/Neck: Scale 1	3 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Head/Neck: Scale 2	2 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Lymphatic system: Scale 2	1 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Pelvic area: Scale 2	2 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Retroperitoneal: Scale 1	3 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Retroperitoneal: Scale 2	4 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Spine: Scale 1	2 subjects	—
Number of Subjects With Additional Diagnostic Gain by Body Region Spine: Scale 2	3 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Confidence in Diagnosis Not confident	6 subjects	1 subjects
Number of Subjects With Confidence in Diagnosis Confident	14 subjects	3 subjects
Number of Subjects With Confidence in Diagnosis Very confident	24 subjects	40 subjects

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment n=44 Participants Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Confidence in Diagnosis by Body Region Abdomen: Confident	1 subjects	1 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Brain: Not confident	1 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Brain: Confident	8 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Brain: Very confident	12 subjects	21 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Chest/Thorax: Confident	1 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Chest/Thorax: Very confident	1 subjects	2 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Head/Neck: Confident	2 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Head/Neck: Very confident	3 subjects	5 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Lymphatic system: Very confident	1 subjects	1 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Pelvic area: Not confident	2 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Pelvic area: Confident	0 subjects	2 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Retroperitoneal: Not confident	3 subjects	1 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Retroperitoneal: Very confident	4 subjects	6 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Spine: Confident	2 subjects	0 subjects
Number of Subjects With Confidence in Diagnosis by Body Region Spine: Very confident	3 subjects	5 subjects

SECONDARY outcome

Timeframe: Up to 4 weeks post-injection

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Final Diagnosis Other diagnoses	24 subjects	—
Number of Subjects With Final Diagnosis Congenital disease/syndrome	6 subjects	—
Number of Subjects With Final Diagnosis No lesions/normal	6 subjects	—
Number of Subjects With Final Diagnosis Malignant lesions	4 subjects	—
Number of Subjects With Final Diagnosis Benign lesions	2 subjects	—
Number of Subjects With Final Diagnosis Infectious disease	1 subjects	—
Number of Subjects With Final Diagnosis Structural malformation	1 subjects	—

SECONDARY outcome

Timeframe: Up to 4 weeks post-injection

Population: Full analysis set (FAS) included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Final Diagnosis by Body Region Abdomen: Other	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Chest/ thorax: Congenital disease/syndrome	3 subjects	—
Number of Subjects With Final Diagnosis by Body Region Chest/ thorax: Infectious disease	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Chest/ thorax: Malignant lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Chest/ thorax: No lesion/Normal	6 subjects	—
Number of Subjects With Final Diagnosis by Body Region Chest/ thorax: Other	2 subjects	—
Number of Subjects With Final Diagnosis by Body Region Brain: Other	10 subjects	—
Number of Subjects With Final Diagnosis by Body Region Head/neck: Benign lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Head/neck: Malignant lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Head/neck: Other	3 subjects	—
Number of Subjects With Final Diagnosis by Body Region Lymphatic system: Other	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Pelvic area: Benign lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Pelvic area: Other	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Retroperitoneal: Congenital disease/syndrome	3 subjects	—
Number of Subjects With Final Diagnosis by Body Region Retroperitoneal: Malignant lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Retroperitoneal: Other	3 subjects	—
Number of Subjects With Final Diagnosis by Body Region Spine: Malignant lesion	1 subjects	—
Number of Subjects With Final Diagnosis by Body Region Spine: Other	3 subjects	—
Number of Subjects With Final Diagnosis by Body Region Spine: Structural malformation	1 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI No	39 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI Yes	5 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Abdomen: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Abdomen: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Brain: No	20 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Brain: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Chest/Thorax: No	2 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Chest/Thorax: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Head/Neck: No	5 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Head/Neck: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Lymphatic system: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Lymphatic system: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Pelvic area: No	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Pelvic area: Yes	2 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Retroperitoneal: No	5 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Retroperitoneal: Yes	2 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Spine: No	5 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region Spine: Yes	0 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis No	33 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis Yes	11 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Brain: No	17 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Brain: Yes	4 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Chest/Thorax: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Abdomen: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Abdomen: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Chest/Thorax: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Head/Neck: No	4 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Head/Neck: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Lymphatic system: No	0 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Lymphatic system: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Pelvic area: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Pelvic area: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Retroperitoneal: No	5 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Retroperitoneal: Yes	2 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Spine: No	4 subjects	—
Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region Spine: Yes	1 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis No	32 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis Yes	12 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Abdomen: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Abdomen: Yes	0 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Brain: No	16 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Brain: Yes	5 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Chest/Thorax: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Chest/Thorax: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Head/Neck: No	4 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Head/Neck: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Lymphatic system: No	0 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Lymphatic system: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Pelvic area: No	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Pelvic area: Yes	1 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Retroperitoneal: No	5 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Retroperitoneal: Yes	2 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Spine: No	4 subjects	—
Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region Spine: Yes	1 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Management From Unenhanced to Combined MRI No	36 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI Yes	8 subjects	—

SECONDARY outcome

Timeframe: Images were taken pre-injection and post-injection (within about 15 minutes)

Population: FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Lymphatic system: No	1 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Abdomen: No	1 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Abdomen: Yes	0 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Brain: No	19 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Brain: Yes	2 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Chest/Thorax: No	2 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Chest/Thorax: Yes	0 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Head/Neck: No	5 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Head/Neck: Yes	0 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Lymphatic system: Yes	0 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Pelvic area: No	0 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Pelvic area: Yes	2 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Retroperitoneal: No	3 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Retroperitoneal: Yes	4 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Spine: No	5 subjects	—
Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region Spine: Yes	0 subjects	—

SECONDARY outcome

Timeframe: Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection

Population: Safety Analysis Set (SAF) included all subjects who received any amount of gadobutrol.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Clinically Significant Abnormal Laboratory Values	0 subjects	—

SECONDARY outcome

Timeframe: Before gadobutrol injection

Population: SAF included all subjects who received any amount of gadobutrol. Here "n" included subjects who were evaluable at specified age group.

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.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection < 1 month (n=5)	61.8 milliliter/minute/1.73 square Standard Deviation 19.2	—
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection 1 to < 2 months (n=4)	91.7 milliliter/minute/1.73 square Standard Deviation 24.8	—
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection 2 to < 6 months (n=9)	136.3 milliliter/minute/1.73 square Standard Deviation 67.1	—
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection 6 to < 12 months (n=11)	115.2 milliliter/minute/1.73 square Standard Deviation 45.9	—
Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection 12 to < 24 months (n=15)	150.4 milliliter/minute/1.73 square Standard Deviation 33.9	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to approximately 7 days after injection

Population: SAF included all subjects who received any amount of gadobutrol.

An Adverse Event (AE) was any untoward medical occurrence in a subject who received study drug. A Serious AE (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly, or deemed significant for any other reason. The drug-relatedness of AEs was determined by the Investigator based on his/her clinical decision based on all available information, and was based on the question whether there was a "reasonable causal relationship" to the study treatment.

Outcome measures

Measure	Overall Study n=44 Participants Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.	Combined MRI Assessment Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.
Number of Subjects With Drug Related Serious and Non- Serious Adverse Events Any study drug-related AE	1 subjects	—
Number of Subjects With Drug Related Serious and Non- Serious Adverse Events Any study drug-related SAE	0 subjects	—

Adverse Events

Overall Study

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Overall Study n=44 participants at risk Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.
Infections and infestations Infected cyst	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Infections and infestations Subdural empyema	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.

Other adverse events

Measure	Overall Study n=44 participants at risk Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.
Gastrointestinal disorders Abnormal faeces	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Gastrointestinal disorders Constipation	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Gastrointestinal disorders Vomiting	4.5% 2/44 • Number of events 3 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
General disorders Catheter site erythema	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
General disorders Pyrexia	11.4% 5/44 • Number of events 5 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Infections and infestations Nasopharyngitis	6.8% 3/44 • Number of events 4 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Infections and infestations Rash pustular	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Infections and infestations Rhinitis	4.5% 2/44 • Number of events 2 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Investigations Body temperature increased	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Investigations Oxygen saturation decreased	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Nervous system disorders Convulsion	2.3% 1/44 • Number of events 2 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Renal and urinary disorders Urine odour abnormal	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Cough	11.4% 5/44 • Number of events 5 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.3% 1/44 • Number of events 2 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Respiratory distress	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.
Respiratory, thoracic and mediastinal disorders Rhonchi	2.3% 1/44 • Number of events 1 • From baseline to approximately 7 days after injection. (S)AEs detailed below are both drug-unrelated and related. One non-serious adverse drug reaction (ADR) of Vomiting was reported in one subject (2.3%). Please refer to "other pre-specified endpoint 41" under "outcome measures.

Additional Information

Therapeutic Area Head

Bayer HealthCare AG

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor is interested in the publication of the results of every study it performs. All relevant aspects regarding publication will be part of the contract between the sponsor and the investigator/institution.
• Publication restrictions are in place

Restriction type: OTHER