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    Clinical Trial Results:
    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 (Gadovist 1.0)

    Summary
    EudraCT number
    		 2010-023003-96
    Trial protocol
    		 DE  
    Global end of trial date
    28 Nov 2013

    Results information
    Results version number
    		 v2(current)
    This version publication date
    07 Sep 2016
    First version publication date
    19 Jun 2015
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    • Correction of full data set
    Bayer sponsor contact information to be updated

    Trial information

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    Trial identification
    Sponsor protocol code
    BAY86-4875/91741
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01544166
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee , Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000994-PIP01-10
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Nov 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Nov 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Nov 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the pharmacokinetics (PK) of gadobutrol at the standard dose of 0.1 millimole per kilogram (mmol/kg) body weight (BW) in pediatric subjects from birth to less than 2 years of age (term newborn infants to toddlers 23 months of age inclusive).
    Protection of trial subjects
    The number of pediatric subjects participating in this study and procedures performed such as blood sampling were minimized as far as feasible. A population-based PK approach was employed allowing sparse sampling for PK analysis.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    United States: 8
    Worldwide total number of subjects
    44
    EEA total number of subjects
    32
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    5
    Infants and toddlers (28 days-23 months)
    39
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 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.

    Pre-assignment
    Screening details
    		 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).

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Overall Study
    Arm description
    		 Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants <2 years of age.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Gadobutrol
    Investigational medicinal product code
    BAY86-4875
    Other name
    Gadovist, Gadavist
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW.

    Number of subjects in period 1
    		Overall Study
    Started
    44
    Treated
    44
    Completed
    44

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall study
    Reporting group description
    		 Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants <2 years of age.

    Reporting group values
    		 Overall study Total
    Number of subjects
    		 44 44
    Age categorical
    Units: Subjects
        Newborns (0-27 days)
    		 5 5
        Infants and toddlers (28 days-23 months)
    		 39 39
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 8.8 ± 7.1 -
    Gender categorical
    Units: Subjects
        Female
    		 18 18
        Male
    		 26 26

    End points

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    End points reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants <2 years of age.

    Subject analysis set title
    Full Analysis Set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    FAS included all subjects who had combined unenhanced and enhanced image sets available regardless of any other protocol deviation.

    Subject analysis set title
    Per-Protocol Set (PPS)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Safety Analysis Set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    SAF included all subjects who received any amount of gadobutrol.

    Subject analysis set title
    Combined MRI Assessment
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Assessment was provided for the combined unenhanced and enhanced image set in all FAS subjects.

    Subject analysis set title
    Unenhanced MRI Assessment
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Assessment was provided for the unenhanced image set alone in all FAS subjects.

    Primary: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual

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    End point title
    		 Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual [1]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [2]
    Units: micromole*hour per liter (micromole*h/L)
        median (full range (min-max))
    776 (544 to 1470)
    Notes
    [2] - PK parameters were analysed using PPS, number of subjects analysed = 43.
    No statistical analyses for this end point

    Primary: Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual

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    End point title
    		 Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual [3]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [4]
    Units: Liter per hour per kilogram [L/(h*kg)]
        median (full range (min-max))
    0.128 (0.0666 to 0.184)
    Notes
    [4] - PK parameters were analysed using PPS, number of subjects analysed = 43.
    No statistical analyses for this end point

    Primary: Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual

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    End point title
    		 Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual [5]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [6]
    Units: Liter per kilogram (L/kg)
        median (full range (min-max))
    0.277 (0.236 to 0.409)
    Notes
    [6] - PK parameters were analysed using PPS, number of subjects analysed = 43.
    No statistical analyses for this end point

    Primary: Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual

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    End point title
    		 Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual [7]
    End point description
    MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.
    End point type
    Primary
    End point timeframe
    Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [8]
    Units: hours
        median (full range (min-max))
    2.18 (1.57 to 4.68)
    Notes
    [8] - PK parameters were analysed using PPS, number of subjects analysed = 43.
    No statistical analyses for this end point

    Primary: Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual

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    End point title
    		 Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual [9]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [10]
    Units: hours
        median (full range (min-max))
    1.62 (1.16 to 3.37)
    Notes
    [10] - PK parameters were analysed using PPS, number of subjects analysed = 43.
    No statistical analyses for this end point

    Primary: Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)

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    End point title
    		 Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20) [11]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    20 minutes post-injection
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [12]
    Units: micromole(s)/liter (micromole/L)
        median (full range (min-max))
    339 (230 to 456)
    Notes
    [12] - PPS. Here number of subjects analysed= 43. C20 was simulated for 2400 virtual paediatric subjects.
    No statistical analyses for this end point

    Primary: Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)

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    End point title
    		 Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30) [13]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    30 minutes post-injection
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not performed since as planned all continuous and ordinal categorical variables were analyzed by descriptive statistics only.
    End point values
    		 Overall Study
    Number of subjects analysed
    43 [14]
    Units: micromole(s)/liter (micromole/L)
        median (full range (min-max))
    292 (194 to 394)
    Notes
    [14] - PPS. Here number of subjects analysed= 43. C30 was simulated for 2400 virtual paediatric subjects.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Anatomical Area Evaluated

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    End point title
    		 Number of Subjects With Anatomical Area Evaluated
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [15]
    44 [16]
    Units: Subjects
        Abdomen: Liver
    1
    1
        Brain: Brain
    20
    20
        Brain: Orbit and brain
    1
    1
        Chest/thorax: Lung
    2
    2
        Head/neck: Head
    3
    3
        Head/neck: Neck
    1
    1
        Head/neck: Skull base/mandible
    1
    1
        Lymphatic system: Right arm
    1
    1
        Pelvic area: Trochanter major, femur neck
    1
    1
        Pelvic area: Testis
    1
    1
        Retroperitoneal: Kidney
    6
    6
        Retroperitoneal: Adrenal gland
    1
    1
        Spine: Spinal cord
    4
    4
        Spine: Lumbar spine
    1
    1
    Notes
    [15] - FAS
    [16] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Technical Adequacy for Diagnosis

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    End point title
    		 Number of Subjects With Technical Adequacy for Diagnosis
    End point description
    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. Number of subjects with any of the score for unenhanced and combined (pre- and post-contrast) MRI sets were reported.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [17]
    44 [18]
    Units: Subjects
        Score = 1
    0
    0
        Score = 2
    0
    0
        Score = 3
    3
    4
        Score = 4
    41
    40
    Notes
    [17] - FAS
    [18] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Technical Adequacy for Diagnosis by Body Region

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    End point title
    		 Number of Subjects With Technical Adequacy for Diagnosis by Body Region
    End point description
    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 (pre- and post-injection) images. Results per body regions were reported. All subjects only have images with score 3 and 4.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [19]
    44 [20]
    Units: Subjects
        Abdomen: Score 4
    1
    1
        Brain: Score 3
    1
    1
        Brain: Score 4
    20
    20
        Chest/thorax: Score 4
    2
    2
        Head/neck: Score 3
    1
    1
        Head/neck: Score 4
    4
    4
        Lymphatic system: Score 4
    1
    1
        Pelvic area: Score 4
    2
    2
        Retroperitoneal area: Score 4
    7
    7
        Spine: Score 3
    1
    2
        Spine: Score 4
    4
    3
    Notes
    [19] - FAS
    [20] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects by Overall Contrast Quality

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    End point title
    		 Number of Subjects by Overall Contrast Quality
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment
    Number of subjects analysed
    44 [21]
    Units: Subjects
        None
    1
        Poor
    0
        Moderate
    0
        Good
    5
        Excellent
    38
    Notes
    [21] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects by Overall Contrast Quality by Body Region

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    End point title
    		 Number of Subjects by Overall Contrast Quality by Body Region
    End point description
    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 on the postcontrast MRI only, which is evaluated together with the unenhanced, this is why it is called combined. Results per body regions were reported. Only subjects with scores "none, good, and excellent" were reported.
    End point type
    Secondary
    End point timeframe
    Images were taken post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment
    Number of subjects analysed
    44 [22]
    Units: Subjects
        Abdomen: Excellent
    1
        Brain: Good
    2
        Brain: Excellent
    19
        Chest/Thorax: Good
    1
        Chest/Thorax: Excellent
    1
        Head/Neck: Excellent
    5
        Lymphatic system: Excellent
    1
        Pelvic area: Excellent
    2
        Retroperitoneal: None
    1
        Retroperitoneal: Good
    1
        Retroperitoneal: Excellent
    5
        Spine: Good
    1
        Spine: Excellent
    4
    Notes
    [22] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Presence of Pathology

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    End point title
    		 Number of Subjects with Presence of Pathology
    End point description
    Presence of pathology was assessed for unenhanced and combined MRI sets and recorded as "yes/no". The number of subjects with presence of pathology for each MRI set was reported. The number of lesions identified for each MRI set was recorded as shown in the endpoint "Number of Subjects With Number of Lesions Detected".
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [23]
    44 [24]
    Units: Subjects
        Yes
    33
    33
        No
    11
    11
    Notes
    [23] - FAS
    [24] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Presence of Pathology by Body Region

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    End point title
    		 Number of Subjects with Presence of Pathology by Body Region
    End point description
    Presence of pathology was assessed for unenhanced and combined MRI sets and recorded as "yes/no". The number of subjects with presence of pathology for each MRI set per body region was reported. The number of lesions identified for each MRI set was recorded. Results per body region were reported. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [25]
    44 [26]
    Units: Subjects
        Abdomen: No
    0
    0
        Abdomen: Yes
    1
    1
        Brain: No
    10
    10
        Brain: Yes
    11
    11
        Chest/Thorax: No
    0
    0
        Chest/Thorax: Yes
    2
    2
        Head/Neck: No
    0
    0
        Head/Neck: Yes
    5
    5
        Lymphatic system: No
    0
    0
        Lymphatic system: Yes
    1
    1
        Pelvic area: No
    0
    0
        Pelvic area: Yes
    2
    2
        Retroperitoneal: No
    0
    0
        Retroperitoneal: Yes
    7
    7
        Spine: No
    1
    1
        Spine: Yes
    4
    4
    Notes
    [25] - FAS
    [26] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Number of Lesions Detected

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    End point title
    		 Number of Subjects With Number of Lesions Detected
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [27]
    44 [28]
    Units: Subjects
        Number of lesions=missing
    1
    2
        Number of lesions=1
    29
    29
        Number of lesions=2
    2
    2
        Number of lesions=10
    1
    0
    Notes
    [27] - 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.
    [28] - 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Number of Lesions Detected by Body Region

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    End point title
    		 Number of Subjects With Number of Lesions Detected by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [29]
    44 [30]
    Units: Subjects
        Abdomen: Missing lesion
    1
    1
        Abdomen: 1 lesion
    0
    0
        Abdomen: 2 lesion
    0
    0
        Abdomen: 10 lesion
    0
    0
        Brain: Missing lesion
    0
    0
        Brain: 1 lesion
    10
    10
        Brain: 2 lesion
    1
    1
        Brain: 10 lesion
    0
    0
        Chest/Thorax: Missing lesion
    0
    0
        Chest/Thorax: 1 lesion
    2
    2
        Chest/Thorax: 2 lesion
    0
    0
        Chest/Thorax: 10 lesion
    0
    0
        Head/Neck: Missing lesion
    0
    1
        Head/Neck: 1 lesion
    4
    4
        Head/Neck: 2 lesion
    0
    0
        Head/Neck: 10 lesion
    1
    0
        Lymphatic system: Missing lesion
    0
    0
        Lymphatic system: 1 lesion
    1
    1
        Lymphatic system: 2 lesion
    0
    0
        Lymphatic system: 10 lesion
    0
    0
        Pelvic area: Missing lesion
    0
    0
        Pelvic area: 1 lesion
    2
    2
        Pelvic area: 2 lesion
    0
    0
        Pelvic area: 10 lesion
    0
    0
        Retroperitoneal: Missing lesion
    0
    0
        Retroperitoneal: 1 lesion
    6
    6
        Retroperitoneal: 2 lesion
    1
    1
        Retroperitoneal: 10 lesion
    0
    0
        Spine: Missing lesion
    0
    0
        Spine: 1 lesion
    4
    4
        Spine: 2 lesion
    0
    0
        Spine: 10 lesion
    0
    0
    Notes
    [29] - 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.
    [30] - 44 subjects in the FAS were analyzed. The number of subjects with presence of pathology was 33.
    No statistical analyses for this end point

    Secondary: Contrast Enhancement in Lesion or Vessel

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    End point title
    		 Contrast Enhancement in Lesion or Vessel
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [31]
    44 [32]
    Units: Subjects
        None
    3
    44
        Moderate
    0
    0
        Good
    6
    0
        Excellent
    35
    0
    Notes
    [31] - FAS
    [32] - FAS
    No statistical analyses for this end point

    Secondary: Contrast Enhancement in Lesion or Vessel by Body Region

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    End point title
    		 Contrast Enhancement in Lesion or Vessel by Body Region
    End point description
    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. Evaluation was done on pre-injection and combined (pre- and post-injection) images. Only subjects with scores "none, good, and excellent" for unenhanced and combined MRI sets were reported.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [33]
    44 [34]
    Units: Subjects
        Abdomen: None
    1
    1
        Blood vessel: None
    0
    2
        Blood vessel: Excellent
    2
    0
        Brain: None
    0
    19
        Brain: Good
    1
    0
        Brain: Excellent
    18
    0
        Chest/Thorax: None
    1
    2
        Chest/Thorax: Good
    1
    0
        Head/Neck: None
    0
    5
        Head/Neck: Good
    1
    0
        Head/Neck: Excellent
    4
    0
        Lymphatic system: None
    0
    1
        Lymphatic system: Excellent
    1
    0
        Pelvic area: None
    0
    2
        Pelvic area: Good
    2
    0
        Retroperitoneal: None
    1
    7
        Retroperitoneal: Excellent
    6
    0
        Spine: None
    0
    5
        Spine: Good
    1
    0
        Spine: Excellent
    4
    0
    Notes
    [33] - FAS
    [34] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Border Delineation of Lesion of Vessel

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    End point title
    		 Number of Subjects With Border Delineation of Lesion of Vessel
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [35]
    44 [36]
    Units: Subjects
        None
    1
    5
        Moderate
    0
    6
        Good
    1
    9
        Excellent
    42
    24
    Notes
    [35] - FAS
    [36] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Border Delineation of Lesion of Vessel by Body Region

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    End point title
    		 Number of Subjects With Border Delineation of Lesion of Vessel by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [37]
    44 [38]
    Units: Subjects
        Abdomen: Excellent
    1
    1
        Blood vessel: Excellent
    2
    2
        Brain: Moderate
    0
    3
        Brain: Good
    0
    6
        Brain: Excellent
    19
    10
        Chest/Thorax: Good
    0
    1
        Chest/Thorax: Excellent
    2
    1
        Head/Neck: Good
    1
    2
        Head/Neck: Excellent
    4
    3
        Lymphatic system: Excellent
    1
    1
        Pelvic area: Moderate
    0
    1
        Pelvic area: Excellent
    2
    1
        Retroperitoneal: None
    1
    3
        Retroperitoneal: Excellent
    6
    4
        Spine: None
    0
    2
        Spine: Moderate
    0
    2
        Spine: Excellent
    5
    1
    Notes
    [37] - FAS
    [38] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects by Lesion Characterization or Homogeneity of Vessel Enhancement

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    End point title
    		 Number of Subjects by Lesion Characterization or Homogeneity of Vessel Enhancement
    End point description
    The degree of information on 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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [39]
    44 [40]
    Units: Subjects
        Poor
    1
    6
        Moderate
    0
    11
        Good
    43
    27
    Notes
    [39] - FAS
    [40] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects by Lesion Characterization or Homogeneity of Vessel Enhancement by Body Region

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    End point title
    		 Number of Subjects by Lesion Characterization or Homogeneity of Vessel Enhancement by Body Region
    End point description
    The degree of information on 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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [41]
    44 [42]
    Units: Subjects
        Abdomen: Good
    1
    1
        Blood vessel: Good
    2
    2
        Brain: Poor
    0
    1
        Brain: Moderate
    0
    5
        Brain: Good
    19
    13
        Chest/Thorax: Moderate
    0
    1
        Chest/Thorax: Good
    2
    1
        Head/Neck: Poor
    0
    1
        Head/Neck: Good
    5
    4
        Lymphatic system: Good
    1
    1
        Pelvic area: Moderate
    0
    2
        Pelvic area: Good
    2
    0
        Retroperitoneal: Poor
    1
    3
        Retroperitoneal: Good
    6
    4
        Spine: Poor
    0
    1
        Spine: Moderate
    0
    3
        Spine: Good
    5
    1
    Notes
    [41] - FAS
    [42] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Diagnoses

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    End point title
    		 Number of Subjects With Diagnoses
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [43]
    44 [44]
    Units: Subjects
        Benign lesion
    2
    1
        Malignant lesion
    4
    4
        Vascular malformation
    1
    1
        Structural malformation
    2
    2
        Inflammation
    3
    2
        Congenital disease / syndrome
    8
    6
        No lesion/Normal
    11
    10
        Other
    13
    18
    Notes
    [43] - FAS
    [44] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Diagnoses by Body Region

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    End point title
    		 Number of Subjects With Diagnoses by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [45]
    44 [46]
    Units: Subjects
        Abdomen: Other
    1
    1
        Brain: Malignant lesion
    1
    1
        Brain: Inflammation
    1
    1
        Brain: Congenital disease/syndrome
    3
    3
        Brain: No lesion/Normal
    10
    9
        Brain: Other
    6
    7
        Chest/Thorax: Structural malformation
    1
    1
        Chest/Thorax: Other
    1
    1
        Head/Neck: Benign lesion
    1
    1
        Head/Neck: Malignant lesion
    1
    1
        Head/Neck: Inflammation
    1
    1
        Head/Neck: Other
    2
    2
        Lymphatic system: Vascular malformation
    1
    1
        Pelvic area: Benign lesion
    1
    0
        Pelvic area: Inflammation
    1
    0
        Pelvic area: Other
    0
    2
        Retroperitoneal: Malignant lesion
    1
    1
        Retroperitoneal: Congenital disease/syndrome
    5
    3
        Retroperitoneal: Other
    1
    3
        Spine: Malignant lesion
    1
    1
        Spine: Structural malformation
    1
    1
        Spine: No lesion/Normal
    1
    1
        Spine: Other
    2
    2
    Notes
    [45] - FAS
    [46] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Additional Diagnostic Gain

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    End point title
    		 Number of Subjects with Additional Diagnostic Gain
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment
    Number of subjects analysed
    44 [47]
    Units: Subjects
        Scale 1
    19
        Scale 2
    24
        Scale 3
    1
    Notes
    [47] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Additional Diagnostic Gain by Body Region

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    End point title
    		 Number of Subjects with Additional Diagnostic Gain by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment
    Number of subjects analysed
    44 [48]
    Units: Subjects
        Abdomen: Scale 2
    1
        Brain: Scale 1
    11
        Brain: Scale 2
    9
        Brain: Scale 3
    1
        Chest/Thorax: Scale 2
    2
        Head/Neck: Scale 1
    3
        Head/Neck: Scale 2
    2
        Lymphatic system: Scale 2
    1
        Pelvic area: Scale 2
    2
        Retroperitoneal: Scale 1
    3
        Retroperitoneal: Scale 2
    4
        Spine: Scale 1
    2
        Spine: Scale 2
    3
    Notes
    [48] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Confidence in Diagnosis

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    End point title
    		 Number of Subjects with Confidence in Diagnosis
    End point description
    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, 3 = Very confident. Evaluation was done on pre-injection and combined (pre- and post-injection) images.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [49]
    44 [50]
    Units: Subjects
        Not confident
    1
    6
        Confident
    3
    14
        Very confident
    40
    24
    Notes
    [49] - FAS
    [50] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects with Confidence in Diagnosis by Body Region

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    End point title
    		 Number of Subjects with Confidence in Diagnosis by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Combined MRI Assessment Unenhanced MRI Assessment
    Number of subjects analysed
    44 [51]
    44 [52]
    Units: Subjects
        Abdomen: Confident
    1
    1
        Brain: Not confident
    0
    1
        Brain: Confident
    0
    8
        Brain: Very confident
    21
    12
        Chest/Thorax: Confident
    0
    1
        Chest/Thorax: Very confident
    2
    1
        Head/Neck: Confident
    0
    2
        Head/Neck: Very confident
    5
    3
        Lymphatic system: Very confident
    1
    1
        Pelvic area: Not confident
    0
    2
        Pelvic area: Confident
    2
    0
        Retroperitoneal: Not confident
    1
    3
        Retroperitoneal: Very confident
    6
    4
        Spine: Confident
    0
    2
        Spine: Very confident
    5
    3
    Notes
    [51] - FAS
    [52] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Final Diagnosis

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    End point title
    		 Number of Subjects With Final Diagnosis
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Up to 4 weeks post-injection
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [53]
    Units: Subjects
        Other diagnoses
    24
        Congenital disease/syndrome
    6
        No lesions/normal
    6
        Malignant lesions
    4
        Benign lesions
    2
        Infectious disease
    1
        Structural malformation
    1
    Notes
    [53] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Final Diagnosis by Body Region

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    End point title
    		 Number of Subjects With Final Diagnosis by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Up to 4 weeks post-injection
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [54]
    Units: Subjects
        Abdomen: Other
    1
        Brain: Other
    10
        Chest/ thorax: No lesion/Normal
    6
        Chest/ thorax: Congenital disease / syndrome
    3
        Chest/ thorax: Other
    2
        Chest/ thorax: Infectious disease
    1
        Chest/ thorax: Malignant lesion
    1
        Head/ neck: Other
    3
        Head/ neck: Benign lesion
    1
        Head/ neck: Malignant lesion
    1
        Lymphatic system: Other
    1
        Pelvic area: Benign lesion
    1
        Pelvic area: Other
    1
        Retroperitoneal: Congenital disease / syndrome
    3
        Retroperitoneal: Other
    3
        Retroperitoneal: Malignant lesion
    1
        Spine: Other
    3
        Spine: Malignant lesion
    1
        Spine: Structural malformation
    1
    Notes
    [54] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI

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    End point title
    		 Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [55]
    Units: Subjects
        No
    39
        Yes
    5
    Notes
    [55] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region

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    End point title
    		 Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [56]
    Units: Subjects
        Abdomen: No
    1
        Abdomen: Yes
    0
        Brain: No
    20
        Brain: Yes
    1
        Chest/Thorax: No
    2
        Chest/Thorax: Yes
    0
        Head/Neck: No
    5
        Head/Neck: Yes
    0
        Lymphatic system: No
    1
        Lymphatic system: Yes
    0
        Pelvic area: No
    0
        Pelvic area: Yes
    2
        Retroperitoneal: No
    5
        Retroperitoneal: Yes
    2
        Spine: No
    5
        Spine: Yes
    0
    Notes
    [56] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis

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    End point title
    		 Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [57]
    Units: Subjects
        No
    33
        Yes
    11
    Notes
    [57] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region

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    End point title
    		 Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region
    End point description
    The analysis value for change in diagnosis was recorded as "yes/no". Results per body regions were reported.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [58]
    Units: Subjects
        Abdomen: No
    1
        Abdomen: Yes
    0
        Brain: No
    17
        Brain: Yes
    4
        Chest/Thorax: No
    1
        Chest/Thorax: Yes
    1
        Head/Neck: No
    4
        Head/Neck: Yes
    1
        Lymphatic system: No
    0
        Lymphatic system: Yes
    1
        Pelvic area: No
    1
        Pelvic area: Yes
    1
        Retroperitoneal: No
    5
        Retroperitoneal: Yes
    2
        Spine: No
    4
        Spine: Yes
    1
    Notes
    [58] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis

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    End point title
    		 Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [59]
    Units: Subjects
        No
    32
        Yes
    12
    Notes
    [59] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region

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    End point title
    		 Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [60]
    Units: Subjects
        Abdomen: No
    1
        Abdomen: Yes
    0
        Brain: No
    16
        Brain: Yes
    5
        Chest/Thorax: No
    1
        Chest/Thorax: Yes
    1
        Head/Neck: No
    4
        Head/Neck: Yes
    1
        Lymphatic system: No
    0
        Lymphatic system: Yes
    1
        Pelvic area: No
    1
        Pelvic area: Yes
    1
        Retroperitoneal: No
    5
        Retroperitoneal: Yes
    2
        Spine: No
    4
        Spine: Yes
    1
    Notes
    [60] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Management From Unenhanced to Combined MRI

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    End point title
    		 Number of Subjects With Change in Management From Unenhanced to Combined MRI
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [61]
    Units: Subjects
        No
    36
        Yes
    8
    Notes
    [61] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region

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    End point title
    		 Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Images were taken pre-injection and post-injection (within about 15 minutes)
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [62]
    Units: Subjects
        Abdomen: No
    1
        Abdomen: Yes
    0
        Brain: No
    19
        Brain: Yes
    2
        Chest/Thorax: No
    2
        Chest/Thorax: Yes
    0
        Head/Neck: No
    5
        Head/Neck: Yes
    0
        Lymphatic system: No
    1
        Lymphatic system: Yes
    0
        Pelvic area: No
    0
        Pelvic area: Yes
    2
        Retroperitoneal: No
    3
        Retroperitoneal: Yes
    4
        Spine: No
    5
        Spine: Yes
    0
    Notes
    [62] - FAS
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormal Laboratory Values

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    End point title
    		 Number of Subjects With Clinically Significant Abnormal Laboratory Values
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [63]
    Units: Subjects
    0
    Notes
    [63] - SAF
    No statistical analyses for this end point

    Secondary: Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection

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    End point title
    		 Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection
    End point description
    The estimated glomerular filtration rate (eGFR) is used to assess the renal function in the pediatric population. eGFR was calculated based on the Schwartz formula with blood sampling for serum creatinine (Scr) not exceeding 14 days prior to gadobutrol injection. If Scr was measured with routine methods that had not been recalibrated to be traceable to isotope dilution mass spectrometry (IDMS), the eGFR was obtained from the original Schwartz formula: eGFR = k * height / Scr; where k is a proportionality constant (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 IDMS, the updated Schwartz formula was used to obtain the eGFR: eGFR = 0.413 * height / Scr. eGFR was reported in the following age groups: < 1 month, 1 to < 2 months, 2 to < 6 months, 6 to < 12 months, and 12 to < 24 months.
    End point type
    Secondary
    End point timeframe
    Before gadobutrol injection
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [64]
    Units: milliliter/minute/1.73 square meters
    arithmetic mean (standard deviation)
        < 1 month (n=5)
    61.8 ± 19.2
        1 to < 2 months (n=4)
    91.7 ± 24.8
        2 to < 6 months (n=9)
    136.3 ± 67.1
        6 to < 12 months (n=11)
    115.2 ± 45.9
        12 to < 24 months (n=15)
    150.4 ± 33.9
    Notes
    [64] - Here "n" included subjects who were evaluable at specified age group.
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Drug Related Serious and Non-Serious Adverse Events

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    End point title
    		 Number of Subjects With Drug Related Serious and Non-Serious Adverse Events
    End point description
    An Adverse Event (AE) was any untoward medical occurrence attributed to study drug in a subject who received study drug. A Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Drug-related adverse events are AEs as determined by the Investigator. The relatedness between adverse events and the administration of treatment was determined by the Investigator based on his/her clinical decision based on all available information. The assessment of the causal relationship to study drug was based on the question whether there was a “reasonable causal relationship” to the study treatment in question.
    End point type
    Other pre-specified
    End point timeframe
    From baseline to approximately 7 days after injection
    End point values
    		 Overall Study
    Number of subjects analysed
    44 [65]
    Units: Subjects
        Any study drug-related AE
    1
        Any study drug-related SAE
    0
    Notes
    [65] - SAF included all subjects who received any amount of gadobutrol.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of informed consent signed up to approximately 7 days after injection.
    Adverse event reporting additional description
    (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 ” in end points section.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 -

    Serious adverse events
    		 Overall Study
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 44 (6.82%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Infected cyst
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subdural empyema
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Overall Study
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 44 (38.64%)
    Investigations
    Body temperature increased
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    2
    General disorders and administration site conditions
    Catheter site erythema
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    5
    Gastrointestinal disorders
    Abnormal faeces
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Constipation
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    2 / 44 (4.55%)
         occurrences all number
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    5
    Pneumothorax
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    2
    Dyspnoea
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Rhonchi
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Respiratory distress
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Renal and urinary disorders
    Urine odour abnormal
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Infections and infestations
    Rash pustular
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    4
    Rhinitis
         subjects affected / exposed
    2 / 44 (4.55%)
         occurrences all number
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Results for Typical PK parameters were provided by the median value of the population together with the min-max range (individual PK). Typical PK parameter as described in study protocol was reflected by the Median PK parameter in the study report.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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