Trial Outcomes & Findings for Safety and Efficacy of Gadobutrol 1.0 Molar ( Gadavist ) in Patients for Central Nervous System (CNS) Imaging (NCT NCT00623467)

NCT ID: NCT00623467

Last Updated: 2014-02-10

Results Overview

BR1 (reader 1 of 3) evaluated the images from the unenhanced magnetic resonance imaging (MRI) in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 343 participants
• Primary outcome timeframe: Up to 2 hours after injection of gadobutrol
• Results posted on: 2014-02-10

Participant Flow

The date of the first participant's first visit was 17 DEC 2007. The date of the last participant's last visit was 12 DEC 2008.

A total of 347 participants were screened for inclusion into the study; 4 participants failed screening because they did not meet the inclusion criteria. Therefore, 343 participants were enrolled into the study and received study drug.

Participant milestones

Measure	Gadobutrol (Gadavist, BAY86-4875) Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Overall Study STARTED	343
Overall Study COMPLETED	336
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Gadobutrol (Gadavist, BAY86-4875) Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Overall Study Lost to Follow-up	1
Overall Study Protocol Violation	4
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Safety and Efficacy of Gadobutrol 1.0 Molar ( Gadavist ) in Patients for Central Nervous System (CNS) Imaging

Baseline characteristics by cohort

Measure	Gadobutrol (Gadavist, BAY86-4875) n=343 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Age, Customized < 45 years	149 participants n=5 Participants
Age, Customized 45 - 64 years	145 participants n=5 Participants
Age, Customized ≥ 65 years	49 participants n=5 Participants
Sex: Female, Male Female	197 Participants n=5 Participants
Sex: Female, Male Male	146 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	68 participants n=5 Participants
Race/Ethnicity, Customized Black	9 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	87 participants n=5 Participants
Race/Ethnicity, Customized Asian	161 participants n=5 Participants
Race/Ethnicity, Customized Other	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: The full analysis set (FAS); which used data from all participants for whom data and images were available for the unenhanced MRI and combined unenhanced and gadobutrol-enhanced MRI, excluding the sample participants (the first participant from each study site).

BR1 (reader 1 of 3) evaluated the images from the unenhanced magnetic resonance imaging (MRI) in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=301 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=301 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1) internal morphology	1.87 scores on a scale Standard Deviation 0.51	2.40 scores on a scale Standard Deviation 0.54
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1) contrast enhancement	0.94 scores on a scale Standard Deviation 0.25	2.96 scores on a scale Standard Deviation 0.80
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1) border delineation	2.17 scores on a scale Standard Deviation 0.57	3.01 scores on a scale Standard Deviation 0.75

PRIMARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR2 (reader 2 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=309 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=309 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 2 (BR2) contrast enhancement	0.93 scores on a scale Standard Deviation 0.27	2.87 scores on a scale Standard Deviation 0.77
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 2 (BR2) border delineation	1.98 scores on a scale Standard Deviation 0.56	3.15 scores on a scale Standard Deviation 0.73
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 2 (BR2) internal morphology	1.38 scores on a scale Standard Deviation 0.43	2.46 scores on a scale Standard Deviation 0.54

PRIMARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR3 (reader 3 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=309 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=309 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 3 (BR3) contrast enhancement	0.93 scores on a scale Standard Deviation 0.25	2.86 scores on a scale Standard Deviation 0.77
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 3 (BR3) border delineation	1.64 scores on a scale Standard Deviation 0.45	2.76 scores on a scale Standard Deviation 0.76
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 3 (BR3) internal morphology	1.49 scores on a scale Standard Deviation 0.39	2.25 scores on a scale Standard Deviation 0.56

PRIMARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=311 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=311 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Average Reader (AR) contrast enhancement	0.93 scores on a scale Standard Deviation 0.23	2.86 scores on a scale Standard Deviation 0.73
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Average Reader (AR) border delineation	1.92 scores on a scale Standard Deviation 0.43	2.94 scores on a scale Standard Deviation 0.68
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Average Reader (AR) internal morphology	1.57 scores on a scale Standard Deviation 0.35	2.35 scores on a scale Standard Deviation 0.49

PRIMARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: FAS

The 3 blinded readers evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another to determine the total number of lesions.

Outcome measures

Measure	Unenhanced n=321 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=321 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers BR1	2.26 lesions Standard Deviation 7.61	2.93 lesions Standard Deviation 8.68
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers BR2	3.77 lesions Standard Deviation 11.79	3.60 lesions Standard Deviation 10.40
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers BR3	1.92 lesions Standard Deviation 7.19	2.37 lesions Standard Deviation 7.26
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers AR	2.65 lesions Standard Deviation 6.30	2.97 lesions Standard Deviation 6.95

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The clinical investigators evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible. The data for "contrast enhancement - unenhanced" were not collected for the clinical investigators.

Outcome measures

Measure	Unenhanced n=312 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=312 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator contrast enhancement	NA scores on a scale Standard Deviation NA The data for "contrast enhancement - unenhanced" were not collected for the clinical investigators.	2.97 scores on a scale Standard Deviation 0.80
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator border delineation	2.51 scores on a scale Standard Deviation 0.75	3.40 scores on a scale Standard Deviation 0.50
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator internal morphology	2.03 scores on a scale Standard Deviation 0.64	2.78 scores on a scale Standard Deviation 0.30

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: FAS

The clinical investigators evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another to determine the total number of lesions.

Outcome measures

Measure	Unenhanced n=321 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=321 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	2.53 lesions Standard Deviation 4.60	2.74 lesions Standard Deviation 4.78

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR1 (reader 1 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=245 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=245 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) contrast enhancement	0.84 scores on a scale Standard Deviation 0.40	2.42 scores on a scale Standard Deviation 1.37
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) border delineation	1.66 scores on a scale Standard Deviation 0.96	2.40 scores on a scale Standard Deviation 1.15
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) internal morphology	1.66 scores on a scale Standard Deviation 0.94	2.11 scores on a scale Standard Deviation 0.88

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR2 (reader 2 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=246 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=246 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) contrast enhancement	0.80 scores on a scale Standard Deviation 0.42	2.28 scores on a scale Standard Deviation 1.26
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) border delineation	1.67 scores on a scale Standard Deviation 0.98	2.79 scores on a scale Standard Deviation 1.21
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) internal morphology	1.19 scores on a scale Standard Deviation 0.74	2.22 scores on a scale Standard Deviation 0.91

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR3 (reader 3 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=248 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=248 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) contrast enhancement	0.81 scores on a scale Standard Deviation 0.41	2.48 scores on a scale Standard Deviation 1.29
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) border delineation	1.07 scores on a scale Standard Deviation 0.71	2.34 scores on a scale Standard Deviation 1.22
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) internal morphology	1.10 scores on a scale Standard Deviation 0.70	2.00 scores on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=273 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=273 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) border delineation	1.42 scores on a scale Standard Deviation 0.77	2.42 scores on a scale Standard Deviation 1.08
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) internal morphology	1.27 scores on a scale Standard Deviation 0.68	2.04 scores on a scale Standard Deviation 0.82
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) contrast enhancement	0.79 scores on a scale Standard Deviation 0.38	2.29 scores on a scale Standard Deviation 1.23

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR1 (reader 1 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=289 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=289 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) contrast enhancement	1.00 scores on a scale Standard Deviation 0.04	3.40 scores on a scale Standard Deviation 0.48
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) border delineation	2.57 scores on a scale Standard Deviation 0.45	3.51 scores on a scale Standard Deviation 0.49
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) internal morphology	2.03 scores on a scale Standard Deviation 0.30	2.65 scores on a scale Standard Deviation 0.35

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR2 (reader 2 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=289 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=289 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) contrast enhancement	1.01 scores on a scale Standard Deviation 0.09	3.36 scores on a scale Standard Deviation 0.39
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) border delineation	2.18 scores on a scale Standard Deviation 0.29	3.45 scores on a scale Standard Deviation 0.38
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2) internal morphology	1.49 scores on a scale Standard Deviation 0.22	2.67 scores on a scale Standard Deviation 0.27

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

BR3 (reader 3 of 3) evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=289 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=289 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) internal morphology	1.79 scores on a scale Standard Deviation 0.16	2.50 scores on a scale Standard Deviation 0.27
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) contrast enhancement	1.00 scores on a scale Standard Deviation 0.05	3.22 scores on a scale Standard Deviation 0.37
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3) border delineation	2.07 scores on a scale Standard Deviation 0.27	3.15 scores on a scale Standard Deviation 0.38

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=289 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=289 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) contrast enhancement	1.01 scores on a scale Standard Deviation 0.04	3.33 scores on a scale Standard Deviation 0.34
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) border delineation	2.28 scores on a scale Standard Deviation 0.27	3.37 scores on a scale Standard Deviation 0.34
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR) internal morphology	1.77 scores on a scale Standard Deviation 0.15	2.61 scores on a scale Standard Deviation 0.24

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. The data for contrast enhancement - gadobutrol combined was shown below.

Outcome measures

Measure	Unenhanced n=284 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Contrast Enhancement for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI by Clinical Investigator	2.84 scores on a scale Standard Deviation 1.24	—

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The clinical investigators evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=285 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=285 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator border delineation	2.44 scores on a scale Standard Deviation 1.01	3.26 scores on a scale Standard Deviation 0.79
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator internal morphology	2.06 scores on a scale Standard Deviation 0.82	2.73 scores on a scale Standard Deviation 0.50

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The clinical investigators evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.

Outcome measures

Measure	Unenhanced n=289 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=289 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator contrast enhancement	NA scores on a scale Standard Deviation NA The data for "contrast enhancement - unenhanced" were not collected for the clinical investigators.	3.47 scores on a scale Standard Deviation 0.50
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator border delineation	2.56 scores on a scale Standard Deviation 0.69	3.55 scores on a scale Standard Deviation 0.41
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator internal morphology	1.97 scores on a scale Standard Deviation 0.65	2.82 scores on a scale Standard Deviation 0.25

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The majority reader diagnosis was the diagnosis provided by at least 2 of the BRs. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the majority reader diagnoses for the combined unenhanced/gadobutrol-enhanced and the unenhanced MR images was the percentage of the exact matches with the final clinical diagnosis.

Outcome measures

Measure	Unenhanced n=224 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=224 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	51.8 per. of the exact diagnostic matches	61.2 per. of the exact diagnostic matches

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the investigator diagnoses for the combined unenhanced/gadobutrol-enhanced and the unenhanced MR images was the percentage of the exact matches with the final clinical diagnosis.

Outcome measures

Measure	Unenhanced n=261 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=261 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	67.0 per. of the exact diagnostic matches	74.3 per. of the exact diagnostic matches

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of abnormal brain tissue.

Outcome measures

Measure	Unenhanced n=239 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=239 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	74.9 percentage of participants	79.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects abnormal brain tissue as defined by the independent truth committee.

Outcome measures

Measure	Unenhanced n=199 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=199 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	75.4 percentage of participants	83.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes abnormal brain tissue as defined by the independent truth committee

Outcome measures

Measure	Unenhanced n=40 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=40 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	72.5 percentage of participants	60.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.

Outcome measures

Measure	Unenhanced n=261 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=261 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	82.4 percentage of participants	87.4 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.

Outcome measures

Measure	Unenhanced n=63 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=63 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	57.1 percentage of participants	77.8 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.

Outcome measures

Measure	Unenhanced n=198 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=198 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	90.4 percentage of participants	90.4 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.

Outcome measures

Measure	Unenhanced n=261 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=261 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	88.9 percentage of participants	92.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.

Outcome measures

Measure	Unenhanced n=63 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=63 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	71.4 percentage of participants	79.4 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: All participants in the FAS with assessments for this outcome measure.

The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.

Outcome measures

Measure	Unenhanced n=198 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=198 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	94.4 percentage of participants	97.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: FAS

The BRs recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident. The AR score was the mean of the means of the 3 BRs.

Outcome measures

Measure	Unenhanced n=321 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=321 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader	2.70 scores on a scale Standard Deviation 0.61	3.13 scores on a scale Standard Deviation 0.64

SECONDARY outcome

Timeframe: Up to 2 hours after injection of gadobutrol

Population: FAS

The investigator recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident.

Outcome measures

Measure	Unenhanced n=321 Participants Participants had diagnostic imaging before receiving any contrast agent	Gadobutrol (Gadavist, BAY86-4875) n=321 Participants Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	2.61 scores on a scale Standard Deviation 0.95	3.45 scores on a scale Standard Deviation 0.74

Adverse Events

Gadobutrol (Gadavist, BAY86-4875)

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gadobutrol (Gadavist, BAY86-4875) n=343 participants at risk Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Nervous system disorders Transient ischaemic attack	0.29% 1/343 • Number of events 1

Other adverse events

Measure	Gadobutrol (Gadavist, BAY86-4875) n=343 participants at risk Participants were administered a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) bolus administration using a power injector via a peripheral vein (an antecubital vein was preferred). Gadobutrol was injected at a rate of 2 mL/second followed by a 20-mL 0.9% saline flush at the same rate.
Gastrointestinal disorders Nausea	2.3% 8/343 • Number of events 8
General disorders Fatigue	1.5% 5/343 • Number of events 5
Investigations Red blood cells urine positive	1.2% 4/343 • Number of events 4
Investigations White blood cells urine positive	1.5% 5/343 • Number of events 5
Nervous system disorders Headache	3.5% 12/343 • Number of events 16

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor is interested in the publication of the results of every study it performs. All relevant aspects regarding publication will be part of the contract between the sponsor and the investigator/institution. The sponsor has committed to the global industry position on disclosure of information about clinical trials. The information regarding the study protocol is made publicly available on the internet at www.clinicaltrials.gov.
• Publication restrictions are in place

Restriction type: OTHER