Trial Outcomes & Findings for Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function (NCT NCT04119843)

NCT ID: NCT04119843

Last Updated: 2025-02-06

Results Overview

Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion border delineation from 1 (poor: lesion border is poorly distinct) to 4 (excellent: lesion border is sharply and clearly distinct). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

87 participants

Primary outcome timeframe

Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0

Results posted on

2025-02-06

Participant Flow

A total of 87 participants were enrolled in 32 study sites in Europe, Asia, North America, and South America between February 2020 and February 2023.

The study consisted of: * Screening Period (Day -28 to Day -1) * Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration) providing a Baseline magnetic resonance imaging (MRI) using an unenhanced MRI examination of the liver * Day of MRI (Day 0) included intake of mangoral after a fast of at least 4 hours and a mangoral-enhanced liver MRI 4 \[±1\] hours after mangoral administration * Follow-up visits following contrast administration (up to Day 7).

Participant milestones

Participant milestones
Measure	Mangoral All participants received a single oral dose of mangoral (800 mg manganese \[II\] chloride tetrahydrate \[MnCl2 4H2O\]). Mangoral is a novel manganese-based contrast agent for liver MRI. Unenhanced MRI of the liver was performed during the Baseline Period, i.e., either on the day prior to the mangoral-enhanced MRI or predose on the same day as the mangoral-enhanced MRI. Mangoral-enhanced MRI of the liver was performed 4 (±1) hours after investigational medicinal product (IMP) administration. Each unenhanced and each mangoral-enhanced liver MRI examination will consist of axial T1- and T2-weighted image sequences and a diffusion-weighted imaging (DWI) sequence.
Overall Study STARTED	87
Overall Study Underwent Unenhanced MRI	85
Overall Study Underwent Mangoral-enhanced MRI	85
Overall Study COMPLETED	83
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Mangoral All participants received a single oral dose of mangoral (800 mg manganese \[II\] chloride tetrahydrate \[MnCl2 4H2O\]). Mangoral is a novel manganese-based contrast agent for liver MRI. Unenhanced MRI of the liver was performed during the Baseline Period, i.e., either on the day prior to the mangoral-enhanced MRI or predose on the same day as the mangoral-enhanced MRI. Mangoral-enhanced MRI of the liver was performed 4 (±1) hours after investigational medicinal product (IMP) administration. Each unenhanced and each mangoral-enhanced liver MRI examination will consist of axial T1- and T2-weighted image sequences and a diffusion-weighted imaging (DWI) sequence.
Overall Study Adverse Event	3
Overall Study Death	1

Baseline Characteristics

Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mangoral n=87 Participants All participants received a single oral dose of mangoral (800 mg). Mangoral is a novel manganese-based contrast agent for liver MRI. Unenhanced MRI of the liver was performed during the Baseline Period, i.e., either on the day prior to the mangoral-enhanced MRI or predose on the same day as the mangoral-enhanced MRI. Mangoral-enhanced MRI of the liver was performed 4 (±1) hours after IMP administration. Each unenhanced and each mangoral-enhanced liver MRI examination will consist of axial T1- and T2-weighted image sequences and a DWI sequence.
Age, Continuous	64.7 years STANDARD_DEVIATION 11.63 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	48 Participants n=5 Participants
Race/Ethnicity, Customized White	28 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0

Population: Full Analysis Set (FAS): All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. The overall number of participants analyzed includes all participants that contributed data for the outcome measure. The number of participants analyzed per row includes only participants with matched lesions (detected and scored on both unenhanced MRI and combined MRI) by each reader.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI Reader 1	3.46 score on a scale Standard Deviation 0.861	2.51 score on a scale Standard Deviation 0.815	—
Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI Reader 2	3.80 score on a scale Standard Deviation 0.607	3.00 score on a scale Standard Deviation 0.952	—
Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI Reader 3	2.97 score on a scale Standard Deviation 0.782	2.31 score on a scale Standard Deviation 0.847	—

PRIMARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0

Population: FAS: All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. The overall number of participants analyzed includes all participants that contributed data for the outcome measure. The number of participants analyzed per row includes only participants with matched lesions (detected and scored on both unenhanced MRI and combined MRI) by each reader.

Visualization of focal liver lesions was measured by 2 co-primary variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion contrast from 1 (poor: difference in signal intensity between the lesion and the surrounding normal liver tissue is poor) to 4 (excellent: difference in signal intensity between the lesion and the surrounding liver is marked). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI Reader 1	3.47 score on a scale Standard Deviation 0.844	2.49 score on a scale Standard Deviation 0.813	—
Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI Reader 2	3.86 score on a scale Standard Deviation 0.417	2.84 score on a scale Standard Deviation 0.926	—
Co-primary Endpoint: Lesion Contrast in Combined MRI Compared to Unenhanced MRI Reader 3	3.33 score on a scale Standard Deviation 0.684	2.51 score on a scale Standard Deviation 0.919	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0; and combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0

Assessments of unenhanced MRI, mangoral-enhanced MRI, and combined MRI for detection of lesions were undertaken by on-site readers (assessing participants at their own site) and during central reading sessions by 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Number of Lesions Detected by Each MRI Method On-site Readers	6.2 lesions Standard Deviation 9.35	5.7 lesions Standard Deviation 9.07	6.4 lesions Standard Deviation 9.57
Number of Lesions Detected by Each MRI Method Reader 1	4.3 lesions Standard Deviation 5.39	3.5 lesions Standard Deviation 5.18	4.2 lesions Standard Deviation 5.19
Number of Lesions Detected by Each MRI Method Reader 2	3.6 lesions Standard Deviation 5.34	3.1 lesions Standard Deviation 5.07	3.2 lesions Standard Deviation 4.85
Number of Lesions Detected by Each MRI Method Reader 3	4.5 lesions Standard Deviation 5.55	4.1 lesions Standard Deviation 5.58	4.3 lesions Standard Deviation 5.59

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Visualization of focal liver lesions was measured by variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion border delineation from 1 (poor: lesion border is poorly distinct) to 4 (excellent: lesion border is sharply and clearly distinct). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	3.34 score on a scale Standard Deviation 0.814	2.57 score on a scale Standard Deviation 0.783	—
Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	3.71 score on a scale Standard Deviation 0.647	2.95 score on a scale Standard Deviation 0.986	—
Lesion Border Delineation in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	2.86 score on a scale Standard Deviation 0.881	2.27 score on a scale Standard Deviation 0.854	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Visualization of focal liver lesions was measured by variables: 'lesion border delineation' and 'lesion contrast' compared to liver background. Qualitative assessment determined on the 4-point scales for up to 15 lesions per participant. Each lesion was assessed for lesion contrast from 1 (poor: difference in signal intensity between the lesion and the surrounding normal liver tissue is poor) to 4 (excellent: difference in signal intensity between the lesion and the surrounding liver is marked). Central reading sessions were undertaken by 3 independent, blinded readers. The scores were calculated for each participant by summing the individual lesion scores and calculating the mean. The total score could range from 1 to 4 for each participant with higher scores representing a better outcome.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	3.53 score on a scale Standard Deviation 0.816	2.80 score on a scale Standard Deviation 0.940	—
Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	3.52 score on a scale Standard Deviation 0.735	2.57 score on a scale Standard Deviation 0.787	—
Lesion Contrast in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	3.18 score on a scale Standard Deviation 0.882	2.46 score on a scale Standard Deviation 0.933	—

SECONDARY outcome

Population: FAS: All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. The number of participants analyzed represents the number of participants with analyzed MRI images. Independent readers analyzed a maximum of 15 lesions per participant.

Each lesion was evaluated on a 3-point scale: 1 (lesion is detected with low confidence), 2 (lesion is detected with moderate confidence), 3 (lesion is detected with high confidence). Higher confidence in lesion detection scores represent better outcomes. Assessments of unenhanced MRI, mangoral-enhanced MRI, and combined MRI for confidence in lesion detection were undertaken by on-site readers (assessing participants are their own site) and during central reading sessions by 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=417 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=387 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI n=397 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Confidence in Lesion Detection Score On-site Readers	2.8 score on a scale Standard Deviation 0.42	2.5 score on a scale Standard Deviation 0.66	2.8 score on a scale Standard Deviation 0.47
Confidence in Lesion Detection Score Reader 1	2.8 score on a scale Standard Deviation 0.53	2.8 score on a scale Standard Deviation 0.54	2.8 score on a scale Standard Deviation 0.57
Confidence in Lesion Detection Score Reader 2	3.0 score on a scale Standard Deviation 0.20	3.0 score on a scale Standard Deviation 0.26	2.9 score on a scale Standard Deviation 0.29
Confidence in Lesion Detection Score Reader 3	2.9 score on a scale Standard Deviation 0.45	2.8 score on a scale Standard Deviation 0.59	2.9 score on a scale Standard Deviation 0.38

SECONDARY outcome

Population: FAS: All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. The number of participants analyzed represents the number of participants with analyzed MRI images. Independent readers analyzed a maximum of 15 lesions per participant.

Each lesion was evaluated on a 3-point scale: 1 (lesion is localized to a liver segment with low confidence), 2 (lesion is localized to a liver segment with moderate confidence), 3 (lesion is localized to a liver segment with high confidence). Assessments of unenhanced MRI, mangoral-enhanced MRI, and combined MRI for confidence in lesion localization were undertaken by on-site readers (assessing participants at their own site) and during central reading sessions by 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=417 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=387 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI n=397 Lesions All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Confidence in Lesion Localization Score On-site Readers	2.9 score on a scale Standard Deviation 0.42	2.5 score on a scale Standard Deviation 0.65	2.8 score on a scale Standard Deviation 0.49
Confidence in Lesion Localization Score Reader 1	2.8 score on a scale Standard Deviation 0.51	2.7 score on a scale Standard Deviation 0.57	2.8 score on a scale Standard Deviation 0.51
Confidence in Lesion Localization Score Reader 2	3.0 score on a scale Standard Deviation 0.20	2.9 score on a scale Standard Deviation 0.30	3.0 score on a scale Standard Deviation 0.19
Confidence in Lesion Localization Score Reader 3	2.9 score on a scale Standard Deviation 0.26	2.9 score on a scale Standard Deviation 0.33	3.0 score on a scale Standard Deviation 0.17

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Assessments of unenhanced MRI and mangoral-enhanced MRI for lesion dimensions were undertaken during central reading sessions by 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Longest Diameter of Largest and Smallest Lesion Largest Lesion: Reader 1	38.2 mm Standard Deviation 29.53	42.2 mm Standard Deviation 32.49	—
Longest Diameter of Largest and Smallest Lesion Smallest Lesion: Reader 1	21.4 mm Standard Deviation 24.20	23.5 mm Standard Deviation 23.75	—
Longest Diameter of Largest and Smallest Lesion Smallest Lesion: Reader 2	25.3 mm Standard Deviation 26.46	27.2 mm Standard Deviation 25.50	—
Longest Diameter of Largest and Smallest Lesion Smallest Lesion: Reader 3	17.0 mm Standard Deviation 23.06	19.8 mm Standard Deviation 23.89	—
Longest Diameter of Largest and Smallest Lesion Largest Lesion: Reader 2	47.9 mm Standard Deviation 36.03	44.5 mm Standard Deviation 31.49	—
Longest Diameter of Largest and Smallest Lesion Largest Lesion: Reader 3	35.2 mm Standard Deviation 27.45	35.5 mm Standard Deviation 31.25	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Population: FAS: All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. As pre-specified in the statistical analysis plan, results are presented for SI enhancement following mangoral-enhanced MRI compared to unenhanced MRI.

Quantitative SI was measured by positioning circular regions of interest in a homogenous area in the liver and the assessed liver lesion on the same image. SI liver was defined as the SI of the liver. Liver SI enhancement (%) = (\[SI liver post contrast - SI liver pre contrast\] / \[SI liver pre contrast\]) × 100. Assessments of unenhanced MRI and mangoral-enhanced MRI for liver SI were undertaken during central reading sessions by the 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Percentage Liver Signal Intensity (SI) Enhancement in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	—	72.159 Percentage SI enhancement Standard Deviation 148.2818	—
Percentage Liver Signal Intensity (SI) Enhancement in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	—	59.633 Percentage SI enhancement Standard Deviation 113.7548	—
Percentage Liver Signal Intensity (SI) Enhancement in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	—	61.456 Percentage SI enhancement Standard Deviation 105.3634	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Quantitative SI was measured by positioning circular regions of interest in a homogenous area in the liver and the assessed liver lesion on the same image. Up to 5 lesions per participant of ≥ 2 cm in diameter were evaluated and these lesions were the same on pre-and post-contrast images. SI lesion was defined as the SI of these lesions. SI liver was defined as the SI of the liver. LLC = (SI liver - SI lesion) / (SI liver + SI lesion). Higher ratio scores represent a better outcome. Assessments of unenhanced MRI and mangoral-enhanced MRI for LLC ratio were undertaken during central reading sessions by the 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Liver-to-lesion Contrast (LLC) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	0.306 ratio Standard Deviation 0.1816	0.143 ratio Standard Deviation 0.1694	—
Liver-to-lesion Contrast (LLC) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	0.291 ratio Standard Deviation 0.2709	0.109 ratio Standard Deviation 0.2739	—
Liver-to-lesion Contrast (LLC) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	0.331 ratio Standard Deviation 0.2162	0.142 ratio Standard Deviation 0.1882	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Quantitative SI was measured by positioning circular regions of interest in a homogenous area in the liver and the assessed liver lesion on the same image. SI liver was defined as the SI of the liver. Standard deviation of the background noise was measured using the largest possible rectangular region of interest vertical to the patient's abdomen in the direction of the phase-encoding gradient. SNR = SI liver / standard deviation noise. Higher ratio scores represent a better outcome. Assessments of unenhanced MRI and mangoral-enhanced MRI for SNR were undertaken during central reading sessions by the 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Signal-to-noise Ratio (SNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	322.951 ratio Standard Deviation 365.1663	286.428 ratio Standard Deviation 581.8717	—
Signal-to-noise Ratio (SNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	531.223 ratio Standard Deviation 1175.7566	226.367 ratio Standard Deviation 362.3748	—
Signal-to-noise Ratio (SNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	419.706 ratio Standard Deviation 694.8662	248.653 ratio Standard Deviation 508.6403	—

SECONDARY outcome

Timeframe: Unenhanced MRI: Baseline Period (Day -1 to Day 0); mangoral-enhanced MRI: 4 hours after mangoral administration on Day 0

Quantitative SI was measured by positioning circular regions of interest in a homogenous area in the liver and the assessed liver lesion on the same image. Up to 5 lesions per participant of ≥ 2 cm in diameter were evaluated and these lesions were the same on pre-and post-contrast images. SI lesion was defined as the SI of these lesions. SI liver was defined as the SI of the liver. Standard deviation of the background noise was measured using the largest possible rectangular region of interest vertical to the patient's abdomen in the direction of the phase-encoding gradient. CNR = (SI liver - mean of SI lesion) / standard deviation noise. Higher ratio scores represent a better outcome. Assessments of unenhanced MRI and mangoral-enhanced MRI for CNR were undertaken during central reading sessions by the 3 independent, blinded readers.

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Contrast-to-noise Ratio (CNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	137.281 ratio Standard Deviation 161.1640	56.564 ratio Standard Deviation 197.1474	—
Contrast-to-noise Ratio (CNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	277.270 ratio Standard Deviation 650.8484	33.506 ratio Standard Deviation 214.2616	—
Contrast-to-noise Ratio (CNR) in Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	241.093 ratio Standard Deviation 510.3520	91.019 ratio Standard Deviation 306.2666	—

SECONDARY outcome

Population: FAS: All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. As pre-specified in the statistical analysis plan, results are presented for change in recommended management following combined MRI and mangoral-enhanced MRI only.

A participant was considered to have a change in recommended management when compared to unenhanced MRI if recommended management was different following assessment of the combined MRI or mangoral-enhanced MRI, including next steps in management (i.e. chemotherapy, surgery, local ablation procedure, combination therapy, or other \[specify\]). Recommended patient management from "other" in unenhanced MRI to "other" in combined MRI or mangoral-enhanced MRI was considered not a change regardless of the free text. Assessments of unenhanced MRI, mangoral-enhanced MRI, and combined MRI for confidence in lesion detection were undertaken by on-site readers (assessing participants at their own site with access to patient records) and during central reading sessions by 3 independent, blinded readers (without access to patient records).

Outcome measures

Outcome measures
Measure	Mangoral-enhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver 4 \[±1\] hours after mangoral administration. Mangoral-enhanced MRI was defined as the reading of the mangoral enhanced MRI only.	Unenhanced MRI n=85 Participants All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). Unenhanced MRI was defined as the reading of the pre-mangoral, unenhanced MRI only.	Combined MRI All participants undertook an unenhanced MRI examination of the liver during the Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration). On the day of MRI (Day 0), all participants received a single oral dose of mangoral (800 mg) after a fast of at least 4 hours and undertook a mangoral-enhanced MRI examination of the liver (paired with unenhanced MRI; combined MRI) 4 \[±1\] hours after mangoral administration. Combined MRI was defined as the paired, simultaneous reading of both unenhanced and mangoral-enhanced MRIs.
Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 2	29 Participants	27 Participants	—
Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI On-site Readers	4 Participants	4 Participants	—
Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 1	21 Participants	19 Participants	—
Number of Participants With Change(s) in Recommended Management Based on Diagnostic Performance of Combined MRI or Mangoral-enhanced MRI Compared to Unenhanced MRI Reader 3	19 Participants	19 Participants	—

Adverse Events

Mangoral

Serious events: 2 serious events

Other events: 41 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Mangoral n=87 participants at risk All participants received a single oral dose of mangoral (800 mg). Mangoral is a novel manganese-based contrast agent for liver MRI. Unenhanced MRI of the liver was performed during the Baseline Period, i.e., either on the day prior to the mangoral-enhanced MRI or predose on the same day as the mangoral-enhanced MRI. Mangoral-enhanced MRI of the liver was performed 4 (±1) hours after IMP administration. Each unenhanced and each mangoral-enhanced liver MRI examination will consist of axial T1- and T2-weighted image sequences and a DWI sequence.
Investigations Electrocardiogram QT prolonged	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
General disorders Multiple organ dysfunction syndrome	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).

Other adverse events

Other adverse events
Measure	Mangoral n=87 participants at risk All participants received a single oral dose of mangoral (800 mg). Mangoral is a novel manganese-based contrast agent for liver MRI. Unenhanced MRI of the liver was performed during the Baseline Period, i.e., either on the day prior to the mangoral-enhanced MRI or predose on the same day as the mangoral-enhanced MRI. Mangoral-enhanced MRI of the liver was performed 4 (±1) hours after IMP administration. Each unenhanced and each mangoral-enhanced liver MRI examination will consist of axial T1- and T2-weighted image sequences and a DWI sequence.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Nervous system disorders Paraesthesia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Metabolism and nutrition disorders Hyperglycaemia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Injury, poisoning and procedural complications Iatrogenic injury	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Injury, poisoning and procedural complications Procedural vomiting	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Vascular disorders Hypotension	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Nausea	16.1% 14/87 • Number of events 15 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Diarrhoea	13.8% 12/87 • Number of events 13 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Vomiting	9.2% 8/87 • Number of events 8 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Abdominal pain	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Retching	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Abdominal discomfort	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Abdominal pain upper	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Gastrointestinal disorders Dyspepsia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood urea increased	3.4% 3/87 • Number of events 7 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood alkaline phosphatase increased	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood magnesium decreased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Haemoglobin decreased	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Neutrophil count increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations White blood cells urine positive	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Aspartate aminotransferase increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood creatine increased	1.1% 1/87 • Number of events 5 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood creatinine increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood glucose decreased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood glucose increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood potassium decreased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood pressure increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Blood pressure systolic increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Breath sounds abnormal	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Electrocardiogram QT prolonged	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Electrocardiogram abnormal	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Heart rate increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations International normalised ratio increased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Investigations Lymphocyte count decreased	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Renal and urinary disorders Haematuria	2.3% 2/87 • Number of events 2 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Renal and urinary disorders Chronic kidney disease	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Renal and urinary disorders Micturition urgency	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Renal and urinary disorders Proteinuria	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Blood and lymphatic system disorders Lymphopenia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Blood and lymphatic system disorders Leukocytosis	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Blood and lymphatic system disorders Leukopenia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
General disorders Asthenia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
General disorders Chills	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
General disorders Fatigue	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
General disorders Pain	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Metabolism and nutrition disorders Hyperkalaemia	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
Skin and subcutaneous tissue disorders Scar pain	1.1% 1/87 • Number of events 1 • Up to Day 7 Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).

Additional Information

Andreas Norlin

Ascelia Pharma AB

Phone: +46 735179119

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place