Comparison of Gadovist 75% Standard Dose to Dotarem at Full Standard Dose

Degree of lesion contrast enhancement is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced).

Lesion border delineation is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation).

Lesion internal morphology is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility)

Number of lesions identified (up to 10) detected by 3 blinded Readers. The mean (SD) number lesions in the Average Reader for gadobutrol and gadoterate in the Full Analysis Set was reported below.

The 3 Blinded Readers had to evaluate if the diagnosis resulting from the combined images was malignant disease or not. Each blinded Reader provided a malignant yes/no response. This was compared to the final diagnosis provided by the Investigator. The majority of Readers (2 or 3 Readers agree) was used to calculate sensitivity, specificity, and accuracy - eg. Final Diagnosis - Malignant (Reader 1-yes, Reader 2-no, Reader 3-yes --- Majority Reader yes) - this would be a match for sensitivity.

The percentage of sensitivity, specificity, and accuracy of detection of malignant disease detected by 3 blinded Readers, gadobutrol versus gadoterate (Full Analysis Set) is reported below for Majority Readers.

Diagnostic confidence detected by 3 blinded Readers, gadobutrol vs gadoterate (Full Analysis Set). Blinded Readers rated their confidence in diagnosis according to a 4-point scale (1 - Not confident; 2 - Somewhat confident; 3 - Confident; 4 - Very confident). Results for the Average Reader are reported below.

Comparison of image quality between gadobutrol and gadoterate detected by 3 blinded Readers (Full Analysis Set). Blinded Readers assessed the image quality of gadobutrol- and gadoterate-enhanced images (randomly assigned as left [L] and right [R] image positions) according to a 5-point scale (1- Image R is worse; 2 - Image R is slightly worse; 3- Image R is similar; 4 - Image R is slightly better; 5 - Image R is better). After unblinding of data, the above codes were translated into the following scale: -2 = Gadobutrol image set is worse ; -1 = Gadobutrol image set is slightly worse ; 0 = Image sets are the same ; 1 = Gadobutrol image set is slightly better; 2 = Gadobutrol image set is better. Results for the Average Reader are reported below.

Comparison of contrast enhancement utilizing an overall contrast enhancement estimation algorithm (Full Analysis Set). The exploratory algorithm analyzed the overall enhancement by comparing the axial T1w (longitudinal relaxation time-weighted) enhanced images to the T1w unenhanced images.

Number of subjects with treatment-emergent adverse events (TEAEs) (Safety Analysis Set). TEAEs are defined as any AEs that increase in intensity or that are newly developed during the TE period for Study Period 1 or Study Period 2, where TE period for Study Period 1 goes from the first study drug administration in Study Period 1 to 24 hours post-injection, and TE period for Study Period 2 from the first study drug administration in Study Period 2 to 24 hours post-injection.