Trial Outcomes & Findings for Efficacy and Safety of Gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) (NCT NCT03996447)

Last Updated: 2025-09-22

Results Overview

The lesion visualization (per patient) was based on 3 co-primary criteria on marching lesions: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with gadopiclenol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each co-criterion was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between Paired \[unenhanced and contrast-enhanced\] images and Pre-contrast \[unenhanced\] images was calculated for each of the 3 co-primary criteria and for each reader.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

260 participants

Primary outcome timeframe

At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI.

Results posted on

2025-09-22

Participant Flow

Among the 260 screened patients, 4 were screen failed. A total of 256 patients were randomized (128 in each arm), of whom 6 discontinued the trial before receiving the first contrast agent. Then 250 patients (125 in each arm) received the first contrast agent and underwent the first MRI (First MRI Period). After a washout period of 2-14 days (Washout Period), 242 patients (120 in the Arm 1 and 122 in the Arm 2) received the second contrast agent and underwent the second MRI (Second MRI Period).

Participant milestones

Participant milestones
Measure	Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadopiclenol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR images obtained in the second MRI Examination Period. Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second	Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadobutrol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the second MRI Examination Period. Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second
First MRI Examination STARTED	128	128
First MRI Examination COMPLETED	125	125
First MRI Examination NOT COMPLETED	3	3
Washout STARTED	125	125
Washout COMPLETED	120	122
Washout NOT COMPLETED	5	3
Second MRI Examination STARTED	120	122
Second MRI Examination COMPLETED	120	122
Second MRI Examination NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadopiclenol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR images obtained in the second MRI Examination Period. Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second	Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI Cross-over study design For each patient in this Arm, he (she) performed the first contrast-enhanced MRI with gadobutrol as contrast agent (First MRI Period). After a washout period of 2-14 days (Washout Period), the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent (Second MRI Period). For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the second MRI Examination Period. Gadobutrol 1Mmol/mL Solution for Injection Vial: single intravenous (IV) bolus injection at a rate of 2ml/second Gadopiclenol: single intravenous (IV) bolus injection at a rate of 2ml/second
First MRI Examination Adverse Event	2	0
First MRI Examination Withdrawal by Subject	1	2
First MRI Examination Protocol Violation	0	1
Washout Adverse Event	2	0
Washout Follow-up unavailable due to COVID-19 pandemic	2	1
Washout Withdrawal by Subject	0	1
Washout Other reason	1	1

Baseline Characteristics

Efficacy and Safety of Gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI n=119 Participants Cross-over study design For Arm 1, the patient performed the first contrast-enhanced MRI with gadopiclenol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent. For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR Images obtained in the Second MRI Examination Period .	Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI n=120 Participants Cross-over study design For Arm 2, the patient performed the first contrast-enhanced MRI with gadobutrol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent. For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the Second MRI Examination Period.	Total n=239 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 13.4 • n=5 Participants	56.1 years STANDARD_DEVIATION 14.2 • n=7 Participants	57.2 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	63 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	57 Participants n=7 Participants	115 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	113 Participants n=5 Participants	109 Participants n=7 Participants	222 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	101 Participants n=5 Participants	98 Participants n=7 Participants	199 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment South Korea	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Belgium	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Hungary	57 participants n=5 Participants	43 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	24 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment Taiwan	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Poland	11 participants n=5 Participants	16 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Italy	10 participants n=5 Participants	12 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Mexico	5 participants n=5 Participants	11 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment France	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Spain	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Weight	77.9 Kg STANDARD_DEVIATION 19.5 • n=5 Participants	78.4 Kg STANDARD_DEVIATION 20.8 • n=7 Participants	78.1 Kg STANDARD_DEVIATION 20.1 • n=5 Participants

PRIMARY outcome

Timeframe: At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI.

Population: Full Analysis Set (FAS) included a total of 239 patients who had both Pre and Paired images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 119 patients in the Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients in the Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (per patient).

Outcome measures

Outcome measures
Measure	Patients With Gadopiclenol Paired Images n=239 Participants The analysis included 239 patients on marching lesions who had both gadopiclenol Paired images and gadopiclonol Pre images: 119 patients of Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients of Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (at patient level). Therefore, the 239 patients with gadopiclenol Paired images are the same patients with gadopiclenol Pre images.	Patients With Gadopiclenol Pre Images n=239 Participants The analysis included 239 patients on marching lesions who had both gadopiclenol Paired images and gadopiclonol Pre images: 119 patients of Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients of Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (at patient level). Therefore, the 239 patients with gadopicleno Pre images are the same patients with gadopiclenol Paired images.
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Contrast enhancement - Reader 1	3.77 mean of a score (on a scale) per patient Standard Error 0.03	1.00 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Border delineation - Reader 1	3.90 mean of a score (on a scale) per patient Standard Error 0.02	2.08 mean of a score (on a scale) per patient Standard Error 0.02
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Border delineation - Reader 2	3.64 mean of a score (on a scale) per patient Standard Error 0.04	1.74 mean of a score (on a scale) per patient Standard Error 1.90
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Border delineation - Reader 3	3.97 mean of a score (on a scale) per patient Standard Error 0.03	2.61 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Internal morphology - Reader 1	3.92 mean of a score (on a scale) per patient Standard Error 0.03	1.66 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Internal morphology - Reader 2	3.65 mean of a score (on a scale) per patient Standard Error 0.03	1.88 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Internal morphology - Reader 3	3.97 mean of a score (on a scale) per patient Standard Error 0.04	2.01 mean of a score (on a scale) per patient Standard Error 0.04
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Contrast enhancement - Reader 2	3.58 mean of a score (on a scale) per patient Standard Error 0.03	1.00 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI Contrast enhancement - Reader 3	3.90 mean of a score (on a scale) per patient Standard Error 0.02	1.00 mean of a score (on a scale) per patient Standard Error 0.02

SECONDARY outcome

Timeframe: At each of two MRI examinations with an interval of 2-14 days between 2 MRI examinations

Population: Per-Protocol Set (PPS) analysis population including a total of 236 patients (117 patients of Arm 1 and 119 patients of Arm 2) with no major protocol deviation who have Paired (combined unenhanced and contrast-enhanced) images for both gadopiclenol and gadobutrol assessable for this secondary outcome mesure for at least one matching lesion for at least one off-site reader. The analysis was based on participants (per patient).

The lesion visualization (per patient) was based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images performed with gadopiclenol and images performed with gadobutrol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each of the 3 lesion visualization co-criteria was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between gadopiclenol scores mean and gadobutrol scores mean was calculated for each of the 3 co-primary criteria and for each reader.

Outcome measures

Outcome measures
Measure	Patients With Gadopiclenol Paired Images n=236 Participants The analysis included 239 patients on marching lesions who had both gadopiclenol Paired images and gadopiclonol Pre images: 119 patients of Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients of Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (at patient level). Therefore, the 239 patients with gadopiclenol Paired images are the same patients with gadopiclenol Pre images.	Patients With Gadopiclenol Pre Images n=236 Participants The analysis included 239 patients on marching lesions who had both gadopiclenol Paired images and gadopiclonol Pre images: 119 patients of Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients of Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (at patient level). Therefore, the 239 patients with gadopicleno Pre images are the same patients with gadopiclenol Paired images.
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Internal morphology - Reader 1	3.93 mean of a score (on a scale) per patient Standard Error 0.02	3.93 mean of a score (on a scale) per patient Standard Error 0.02
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Contrast enhancement - Reader 1	3.78 mean of a score (on a scale) per patient Standard Error 0.04	3.77 mean of a score (on a scale) per patient Standard Error 0.04
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Contrast enhancement - Reader 2	3.57 mean of a score (on a scale) per patient Standard Error 0.04	3.52 mean of a score (on a scale) per patient Standard Error 0.04
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Contrast enhancement - Reader 3	3.89 mean of a score (on a scale) per patient Standard Error 0.03	3.81 mean of a score (on a scale) per patient Standard Error 0.03
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Border delineation - Reader 1	3.91 mean of a score (on a scale) per patient Standard Error 0.02	3.93 mean of a score (on a scale) per patient Standard Error 0.02
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Border delineation - Reader 2	3.64 mean of a score (on a scale) per patient Standard Error 0.04	3.60 mean of a score (on a scale) per patient Standard Error 0.04
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Border delineation - Reader 3	3.97 mean of a score (on a scale) per patient Standard Error 0.01	3.95 mean of a score (on a scale) per patient Standard Error 0.01
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Internal morphology - Reader 2	3.64 mean of a score (on a scale) per patient Standard Error 0.04	3.62 mean of a score (on a scale) per patient Standard Error 0.04
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI Internal morphology - Reader 3	3.97 mean of a score (on a scale) per patient Standard Error 0.02	3.92 mean of a score (on a scale) per patient Standard Error 0.02

Adverse Events

Gadopiclenol

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Gadobutrol

Serious events: 1 serious events

Other events: 42 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Gadopiclenol n=247 participants at risk AEs reported after MRI with gadopiclenol	Gadobutrol n=245 participants at risk AEs reported after MRI with gadobutrol
General disorders General Physical Health Deterioration	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)

Other adverse events

Additional Information

Jing Hao, MD, Global Head of Medical Affairs & Clinical Development

Guerbet

Phone: +33 (0) 1 45 91 50 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Gadopiclenol n=247 participants at risk AEs reported after MRI with gadopiclenol	Gadobutrol n=245 participants at risk AEs reported after MRI with gadobutrol
General disorders Injection site pain	2.0% 5/247 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	2.0% 5/245 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site bruising	1.2% 3/247 • Number of events 3 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	1.2% 3/245 • Number of events 3 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site erythema	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	1.2% 3/245 • Number of events 3 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site coldness	0.81% 2/247 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site warmth	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.82% 2/245 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site haematoma	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site haemorrhage	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.82% 2/245 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site paraesthesia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Vessel puncture site haemorrhage	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.82% 2/245 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Asthenia	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Drug ineffective	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Fatigue	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Feeling hot	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site discomfort	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site extravasation	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site hypoaesthesia	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Injection site oedema	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
General disorders Pyrexia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Nervous system disorders Headache	0.81% 2/247 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	2.0% 5/245 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Nervous system disorders Dizziness	2.0% 5/247 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Nervous system disorders Dysgeusia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.82% 2/245 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Nervous system disorders Partial seizures	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.82% 2/245 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Investigations Blood creatinine increased	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	2.0% 5/245 • Number of events 5 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Investigations Blood phosphorus decreased	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Investigations Neutrophil count increased	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Gastrointestinal disorders Nausea	1.6% 4/247 • Number of events 4 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Gastrointestinal disorders Paraesthesia oral	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Gastrointestinal disorders Vomiting	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Skin and subcutaneous tissue disorders Dermatitis contact	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Skin and subcutaneous tissue disorders Erythema	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Musculoskeletal and connective tissue disorders Myofascial pain syndrome	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Musculoskeletal and connective tissue disorders Pain in extremity	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Infections and infestations Sinusitis	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Infections and infestations Upper respiratory tract infection	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Injury, poisoning and procedural complications Incorrect dose administered	0.81% 2/247 • Number of events 2 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Psychiatric disorders Claustrophobia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Psychiatric disorders Sleep disorder	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Blood and lymphatic system disorders Anaemia macrocytic	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Cardiac disorders Tachycardia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Eye disorders Scleral haemorrhage	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Metabolism and nutrition disorders Hypoglycaemia	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/247 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.41% 1/245 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)
Vascular disorders Pallor	0.40% 1/247 • Number of events 1 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)	0.00% 0/245 • Adverse events were recorded from informed consent signature up to one day after the second MRI (i.e., minimum of 4 days and a maximum of 23 days)