Central Nervous System Pathology
Conditions
Keywords
CNS
Brief summary
Researchers in this study want to find the appropriate dose of drug BAY1747846 for adults undergoing MRI for known or highly suspected brain and/or spinal cord conditions so that the image quality is similar to that of drug gadobutrol for adults undergoing MRI. MRI stands for Magnetic resonance imaging which produces body pictures created by using magnetic energy rather than x-ray energy. Both BAY1747846 and gadobutrol are medicinal products known as gadolinium-based contrast agents (GBCA) which are used in MRI examinations to provide contrast enhancement and improve imaging performance. Gadobutrol (brand name: Gadavist, Gadovist) has been approved worldwide for the diagnosis of various disorders in adult and pediatric patients. BAY1747846 is a new GBCA under development with the goal to provide similar imaging performances in MRI. Participants in this study will receive both BAY1747846 and gadobutrol with a period of 3 - 14 days in between. A MRI examination will be performed after each injection. Participant will stay in this study for 2 - 4 weeks depending on the scheduling of the visits.
Interventions
Solution for IV injection, single dose
Solution for IV injection, single dose
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
This is a one-way crossover study with blinded participants and blinded image readers
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be at least 18 years of age at the time of signing the informed consent. * Known or highly suspected CNS pathology (contrast-enhancing CNS lesion) referred for contrast-enhanced MRI of the CNS. * Male and female. * Estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m\^2.
Exclusion criteria
* Considered clinically unstable or has a concomitant/intercurrent condition (e.g. COVID-19 infection) that would not allow participation for the full planned study period (i.e. period 1, 2 or both) in the judgement of the investigator. * Severe cardiovascular disease. * Patients undergoing liver transplantation. * Any contraindication to MRI examinations. * History of severe allergic or anaphylactic/anaphylactoid reaction to any allergen including drugs and contrast agents, foods, chemicals or other substances. * History of allergic asthma and/ or atopic dermatitis. * Suspected lesions or suffering from any of the following CNS diseases/lesion types as the main indication for MRI: * Lepto-meningeal disease (e.g. leptomeningeal carcinomatosis). Dural lesions (e.g. meningiomas) fulfilling inclusion criteria #2 are not excluded * Pituitary adenomas (macro and micro) * Tumors of the choroid plexus * Tumors of the pineal gland * Dermoid/epidermoid tumors * Infectious disease (e.g. brain abscess, cisticercosis, etc.) * Venous angiomas * Subacute/chronic ischemia * Encephalitis * Multiple sclerosis (acute and chronic) * Optic neuritis * Chordomas * Von Hippel Lindau syndrome * Hypertensive leukoencephalopathy. * Receipt of any contrast agent \< 72 h prior to the study MRIs, or planned receipt of any contrast agent within 72 h after the second study MRI. * Planned or expected biopsy in the region of interest or any interventional therapeutic procedure from the first study MRI up to 24 h after the second study MRI. * Planned or expected change in any treatment or procedure between the two study MRIs that may alter image comparability and /or chemotherapy which is changed between the two MRI procedures. * Contraindications to the administration of gadobutrol, as specified in the local product label.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Diagnostic Preference | At 5 minute post each injection | Overall diagnostic preference using a matched pairs approach was evaluated by 3 blinded readers using an ordinal 5-point scale (greatly prefer gadoquatrane, prefer gadoquatrane, no preference, prefer gadobutrol, greatly prefer gadobutrol). Percentage of participants and the respective Wald confidence intervals (CI) for image preference were reported for each of the 3 readers based on the 3-point preference scale (1=greatly prefer/prefer gadoquatrane, 0=no preference, -1=greatly prefer/prefer gadobutrol). If 2 or 3 readers reach the same conclusion on the recommended action (e.g. no dose adjustment needed), then this will be the recommended action taken. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Lesion Visualization Parameters on Post-contrast Images | At 5 minute post each injection | The 3 lesion visualization parameters (border delineation/degree of contrast enhancement/internal morphology) were combined by adding them up for each participant and each blinded reader, leading to only one variable on an ordinal 11-point scale (the higher values represent a better lesion visualization). Average reader was the mean of the 3 blinded readers averages of the scores per participant. Lesion border delineation: measured on a 4-point scale (1=None \[no/unclear delineation of the lesion boundaries\] to 4=Excellent \[clear and complete delineation\]). Degree of lesion contrast enhancement: measured on a 4-point scale (1=No \[lesion is not enhanced\] to 4=Excellent \[lesion is clearly and brightly enhanced\]). Lesion internal morphology: measured on a 3-point scale (1=Poor \[structure and internal morphology of the lesion is poorly visible\] to 3=Good \[structure and internal morphology of the lesion is sufficiently visible\]). |
| Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | At pre-injection and 5 minute post each injection | Lesion border delineation: up to 5 of the largest lesions were selected and scored using a 4-point scale (1=None \[no/unclear delineation of the lesion boundaries\] to 4=Excellent \[clear and complete delineation\]; the higher values represent a better lesion border delineation). Average reader was the mean of the 3 blinded readers averages of the scores per participant. |
| Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | At pre-injection and 5 minute post each injection | Degree of lesion contrast enhancement: up to the 5 largest lesions were selected and scored using a 4-point scale (1=No \[lesion is not enhanced\] to 4=Excellent \[lesion is clearly and brightly enhanced\]; the higher values represent a better degree of lesion contrast enhancement). Average reader was the mean of the 3 blinded readers averages of the scores per participant. |
| Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | At pre-injection and 5 minute post each injection | Lesion internal morphology: up to 5 of the largest lesions were selected and scored using a 3-point scale (1=Poor \[structure and internal morphology of the lesion is poorly visible\] to 3=Good \[structure and internal morphology of the lesion is sufficiently visible\]; the higher values represent a better lesion internal morphology). Average reader was the mean of the 3 blinded readers averages of the scores per participant. |
| Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | At pre-injection and 5 minute post injection | The 3 blinded readers recorded the total number of lesions for each pre-contrast and combined pre- and post-contrast magnetic resonance image set separately. The numbers of participants by number of detected lesions were reported. |
Countries
Bulgaria, Germany, Japan, United States
Participant flow
Recruitment details
Study was conducted at 17 study centers in 4 countries between 18-Nov-2020 (first participant first visit) and 6-Sep-2022 (last participant last visit).
Pre-assignment details
Of the 62 screened participants 5 were screening failures, resulting in 57 participants assigned to treatment who started with gadobutrol.
Participants by arm
| Arm | Count |
|---|---|
| Gadobutrol + Gadoquatrane Participants received one intravenous (IV) injection of gadobutrol 0.1 millimole(s) gadolinium/kilogram body weight (mmol Gd/kg bw) during treatment Period 1 and one IV injection of gadoquatrane (BAY1747846) 0.04 mmol Gd/kg bw during treatment Period 2. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 - Gadobutrol | Withdrawal by Subject | 1 |
| Period 2 - Gadoquatrane | Protocol Violation | 1 |
| Washout 3-14 Days | Pre-specified withdrawal criterion met | 1 |
| Washout 3-14 Days | Progressive disease | 1 |
| Washout 3-14 Days | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gadobutrol + Gadoquatrane |
|---|---|
| Age, Continuous | 55.9 Years STANDARD_DEVIATION 13.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 52 |
| other Total, other adverse events | 3 / 57 | 2 / 52 |
| serious Total, serious adverse events | 0 / 57 | 0 / 52 |
Outcome results
Primary
Overall Diagnostic Preference
Overall diagnostic preference using a matched pairs approach was evaluated by 3 blinded readers using an ordinal 5-point scale (greatly prefer gadoquatrane, prefer gadoquatrane, no preference, prefer gadobutrol, greatly prefer gadobutrol). Percentage of participants and the respective Wald confidence intervals (CI) for image preference were reported for each of the 3 readers based on the 3-point preference scale (1=greatly prefer/prefer gadoquatrane, 0=no preference, -1=greatly prefer/prefer gadobutrol). If 2 or 3 readers reach the same conclusion on the recommended action (e.g. no dose adjustment needed), then this will be the recommended action taken.
Time frame: At 5 minute post each injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance (MR) image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 1 (1) | 10 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 1 (0) | 34 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 1 (-1) | 56 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 2 (1) | 26 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 2 (0) | 42 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 2 (-1) | 32 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 3 (1) | 30 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 3 (0) | 28 Percentage of participants |
| Gadobutrol + Gadoquatrane | Overall Diagnostic Preference | Reader 3 (-1) | 42 Percentage of participants |
Comparison: Reader 1p-value: <0.0001McNemar
Comparison: Reader 2p-value: 0.5775McNemar
Comparison: Reader 3p-value: 0.3173McNemar
Secondary
Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images
Lesion border delineation: up to 5 of the largest lesions were selected and scored using a 4-point scale (1=None \[no/unclear delineation of the lesion boundaries\] to 4=Excellent \[clear and complete delineation\]; the higher values represent a better lesion border delineation). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
Time frame: At pre-injection and 5 minute post each injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.83 Scores on a scale | Standard Deviation 0.701 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.70 Scores on a scale | Standard Deviation 0.509 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 1.98 Scores on a scale | Standard Deviation 0.423 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Average reader | 1.82 Scores on a scale | Standard Deviation 0.438 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.45 Scores on a scale | Standard Deviation 0.589 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 3.28 Scores on a scale | Standard Deviation 0.751 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Average reader | 3.02 Scores on a scale | Standard Deviation 0.614 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 3.39 Scores on a scale | Standard Deviation 0.936 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 1.87 Scores on a scale | Standard Deviation 0.403 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.67 Scores on a scale | Standard Deviation 0.469 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Average reader | 1.81 Scores on a scale | Standard Deviation 0.394 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.88 Scores on a scale | Standard Deviation 0.698 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Average reader | 2.91 Scores on a scale | Standard Deviation 0.609 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.39 Scores on a scale | Standard Deviation 0.576 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 3.28 Scores on a scale | Standard Deviation 0.97 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Border Delineation on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 3.21 Scores on a scale | Standard Deviation 0.873 |
Comparison: Average Reader95% CI: [1.06, 1.34]
Comparison: Average Reader95% CI: [0.94, 1.25]
Secondary
Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images
Degree of lesion contrast enhancement: up to the 5 largest lesions were selected and scored using a 4-point scale (1=No \[lesion is not enhanced\] to 4=Excellent \[lesion is clearly and brightly enhanced\]; the higher values represent a better degree of lesion contrast enhancement). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
Time frame: At pre-injection and 5 minute post each injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.50 Scores on a scale | Standard Deviation 0.629 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 3.55 Scores on a scale | Standard Deviation 0.904 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 3.07 Scores on a scale | Standard Deviation 0.638 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 3.24 Scores on a scale | Standard Deviation 0.917 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 0.99 Scores on a scale | Standard Deviation 0.078 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 1.00 Scores on a scale | Standard Deviation 0.027 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.00 Scores on a scale | Standard Deviation 0 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 3.05 Scores on a scale | Standard Deviation 0.6 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.57 Scores on a scale | Standard Deviation 0.587 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 3.20 Scores on a scale | Standard Deviation 0.825 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Contrast Enhancement on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 3.49 Scores on a scale | Standard Deviation 0.925 |
Comparison: Average Reader95% CI: [1.87, 2.28]
Comparison: Average Reader95% CI: [1.86, 2.25]
Secondary
Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images
Lesion internal morphology: up to 5 of the largest lesions were selected and scored using a 3-point scale (1=Poor \[structure and internal morphology of the lesion is poorly visible\] to 3=Good \[structure and internal morphology of the lesion is sufficiently visible\]; the higher values represent a better lesion internal morphology). Average reader was the mean of the 3 blinded readers averages of the scores per participant.
Time frame: At pre-injection and 5 minute post each injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.27 Scores on a scale | Standard Deviation 0.444 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.05 Scores on a scale | Standard Deviation 0.185 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 1.05 Scores on a scale | Standard Deviation 0.221 |
| Gadobutrol + Gadoquatrane | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 1.13 Scores on a scale | Standard Deviation 0.194 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.13 Scores on a scale | Standard Deviation 0.598 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 2.45 Scores on a scale | Standard Deviation 0.677 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 2.39 Scores on a scale | Standard Deviation 0.493 |
| Gadoquatrane Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 2.62 Scores on a scale | Standard Deviation 0.693 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 1.04 Scores on a scale | Standard Deviation 0.234 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 1.05 Scores on a scale | Standard Deviation 0.211 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 1.16 Scores on a scale | Standard Deviation 0.218 |
| Gadoquatrane Pre-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 1.40 Scores on a scale | Standard Deviation 0.484 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Average Reader | 2.35 Scores on a scale | Standard Deviation 0.5 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 | 2.11 Scores on a scale | Standard Deviation 0.689 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 | 2.58 Scores on a scale | Standard Deviation 0.655 |
| Gadoquatrane Combined Pre- and Post-contrast | Lesion Visualization Parameter Internal Morphology on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 | 2.44 Scores on a scale | Standard Deviation 0.673 |
Comparison: Average Reader95% CI: [1.11, 1.43]
Comparison: Average Reader95% CI: [1.05, 1.32]
Secondary
Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images
The 3 blinded readers recorded the total number of lesions for each pre-contrast and combined pre- and post-contrast magnetic resonance image set separately. The numbers of participants by number of detected lesions were reported.
Time frame: At pre-injection and 5 minute post injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=0) | 4 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=1) | 43 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=2) | 3 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=3) | 0 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=0) | 4 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=1) | 42 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=2) | 0 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=3) | 2 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=0) | 10 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=1) | 40 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=2) | 0 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=3) | 0 Participants |
| Gadobutrol + Gadoquatrane | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=4) | 0 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=3) | 2 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=4) | 0 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=2) | 7 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=3) | 3 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=2) | 7 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=0) | 1 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=1) | 41 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=0) | 1 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=1) | 43 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=0) | 0 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=1) | 40 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=3) | 1 Participants |
| Gadoquatrane Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=2) | 3 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=2) | 1 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=3) | 2 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=0) | 5 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=4) | 0 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=1) | 42 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=2) | 0 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=3) | 0 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=3) | 2 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=0) | 9 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=1) | 40 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=0) | 7 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=1) | 40 Participants |
| Gadoquatrane Pre-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=2) | 1 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=1) | 42 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=3) | 3 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=3) | 2 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=0) | 1 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=2) | 3 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=1) | 43 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=2) | 6 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 1 (Nr. of lesions=1) | 41 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 2 (Nr. of lesions=0) | 0 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=0) | 1 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=4) | 2 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=3) | 1 Participants |
| Gadoquatrane Combined Pre- and Post-contrast | Number of Lesions on Pre-contrast and Combined Pre- and Post-contrast Images | Reader 3 (Nr. of lesions=2) | 4 Participants |
Secondary
Sum of Lesion Visualization Parameters on Post-contrast Images
The 3 lesion visualization parameters (border delineation/degree of contrast enhancement/internal morphology) were combined by adding them up for each participant and each blinded reader, leading to only one variable on an ordinal 11-point scale (the higher values represent a better lesion visualization). Average reader was the mean of the 3 blinded readers averages of the scores per participant. Lesion border delineation: measured on a 4-point scale (1=None \[no/unclear delineation of the lesion boundaries\] to 4=Excellent \[clear and complete delineation\]). Degree of lesion contrast enhancement: measured on a 4-point scale (1=No \[lesion is not enhanced\] to 4=Excellent \[lesion is clearly and brightly enhanced\]). Lesion internal morphology: measured on a 3-point scale (1=Poor \[structure and internal morphology of the lesion is poorly visible\] to 3=Good \[structure and internal morphology of the lesion is sufficiently visible\]).
Time frame: At 5 minute post each injection
Population: Full analysis set (FAS): All participants who have completed magnetic resonance image datasets that qualify for blinded read.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol + Gadoquatrane | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 1 | 9.95 Scores on a scale | Standard Deviation 1.447 |
| Gadobutrol + Gadoquatrane | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 2 | 7.67 Scores on a scale | Standard Deviation 1.292 |
| Gadobutrol + Gadoquatrane | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 3 | 9.28 Scores on a scale | Standard Deviation 1.877 |
| Gadobutrol + Gadoquatrane | Sum of Lesion Visualization Parameters on Post-contrast Images | Average reader | 9.00 Scores on a scale | Standard Deviation 1.294 |
| Gadoquatrane Post-contrast | Sum of Lesion Visualization Parameters on Post-contrast Images | Average reader | 8.94 Scores on a scale | Standard Deviation 1.229 |
| Gadoquatrane Post-contrast | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 1 | 9.67 Scores on a scale | Standard Deviation 1.541 |
| Gadoquatrane Post-contrast | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 3 | 9.65 Scores on a scale | Standard Deviation 1.598 |
| Gadoquatrane Post-contrast | Sum of Lesion Visualization Parameters on Post-contrast Images | Reader 2 | 7.49 Scores on a scale | Standard Deviation 1.406 |
Comparison: Average readerp-value: <0.000195% CI: [-0.24, 0.13]t-test, 1 sided