Safety and Efficacy of MultiHance in Pediatric Patients

• Sponsor: Bracco Diagnostics, Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00323310
• Collaborator: (none)
• Enrollment: 92
• Location: 1
• Arm: 1
• Duration (Months): 29
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the safety and enhancing properties of the magnetic resonance imaging (MRI) contrast agent MultiHance in children aged 2 to 17 years having central nervous system (CNS) disorders.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Diseases	Drug: gadobenate dimeglumine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase III Multi-Center Open Label Study to Evaluate Safety and Efficacy of MultiHance at the Dose of 0.10 mmol/kg in Magnetic Resonance Imaging of the Central Nervous System in Pediatric Patients
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gadobenate Dimeglumine	Drug: gadobenate dimeglumine; A dose of 0.10 mmol/kg (i.e., 0.2 mL/kg) of 0.5 molar MultiHance was injected intravenously at a rate of 2 mL/sec as a single dose.; Other Names: MultiHance

Outcome Measures

Primary Outcome Measures

1. Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1 [pre-dose and immediately postdose]

   5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose

2. Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2 [pre-dose and immediately postdose]

   5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose

3. Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3 [pre-dose and immediately postdose]

   5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose

4. Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1 [pre-dose to immediately post dose]

   5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose

5. Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2 [pre-dose to immediately post dose]

   5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose

6. Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3 [pre-dose to immediately postdose]

   5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose

7. Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1 [pre-dose and immediately postdose]

   5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose

8. Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2 [pre-dose to immediately postdose]

   5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose

9. Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3 [pre-dose to immediately postdose]

   5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose

10. The Number of Patients Administered MultiHance (Gadobenate Dimeglumine) Reporting Adverse Events [up to 72 hours post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Between 2 and 17 years of age

• Informed consent from parents

• Assent from patient where required

• Known or highly suspected disease of the CNS and referred for either cranial or spinal MRI examination

Exclusion Criteria:

• Contraindication to MRI

• Undergoing MRI in an emergency situation

• Known allergy to one or more of the ingredients in MultiHance

• Sickle cell anemia moderate to severe renal impairment

• Received another investigational compound within 30 days

• Pregnancy

• Lactating females

• Likely to undergo an invasive procedure within 72 hours of receiving MultiHance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bracco Diagnostics, Inc.	Princeton	New Jersey	United States	08540

Sponsors and Collaborators

• Bracco Diagnostics, Inc

Investigators

• Study Director: Gianpaolo Pirovano, M.D., Bracco Diagnostics, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00323310
• Other Study ID Numbers: MH 110
• First Posted: May 9, 2006
• Last Update Posted: Oct 22, 2010
• Last Verified: Oct 1, 2010

• Keywords provided by , ,: disease of the central nervous system (brain or spine)
• Additional relevant MeSH terms: Nervous System Diseases; Central Nervous System Diseases

Study Results

Participant Flow

Recruitment Details	Patients were recruited from April 2006 to July 2008 at 17 investigational sites. The blinded read was conducted from September 12, 2008 to September 26, 2008.
Pre-assignment Detail	94 patients enrolled; 92 patients dosed.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Period Title: Overall Study
STARTED	92
COMPLETED	89
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Overall Participants	92
Age (Count of Participants)
<=18 years	92 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.59 (4.017)
Sex: Female, Male (Count of Participants)
Female	47 51.1%
Male	45 48.9%
Region of Enrollment (participants) [Number]
United States	35 38%
Europe	47 51.1%
Canada	1 1.1%
China	9 9.8%

Outcome Measures

1. Primary Outcome

Title	Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1
Description	5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose and immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	148
Predose	1.7 (1.16)
Pre+Postdose	3.0 (1.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.5
	Parameter Dispersion	Type: Standard Deviation; Value: 1.46
	Estimation Comments

2. Primary Outcome

Title	Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2
Description	5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose and immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	135
Predose	1.9 (1.15)
Pre+Postdose	3.1 (1.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.4
	Parameter Dispersion	Type: Standard Deviation; Value: 1.45
	Estimation Comments

3. Primary Outcome

Title	Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3
Description	5-point scale (0=no delineation of lesion borders [lesion not identified in image, lesion borders not visible]; 1=poor border delineation [all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema]; 2=moderate border delineation [border delineation fair/not complete, lesion not clearly separated]; 3=good border delineation [border delineation complete, lesion adequately separated]; 4=excellent border delineation [borders sharply/clearly distinct, lesion sharply separated]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose and immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	131
Predose	1.7 (1.19)
Pre+Postdose	2.4 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; 0.4 to 0.9
	Parameter Dispersion	Type: Standard Deviation; Value: 1.42
	Estimation Comments

4. Primary Outcome

Title	Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1
Description	5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose to immediately post dose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	148
Predose	1.9 (1.18)
Pre+Postdose	3.2 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.6
	Parameter Dispersion	Type: Standard Deviation; Value: 1.56
	Estimation Comments

5. Primary Outcome

Title	Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2
Description	5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose to immediately post dose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	135
Predose	2.1 (1.17)
Pre+Postdose	3.2 (1.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.4
	Parameter Dispersion	Type: Standard Deviation; Value: 1.49
	Estimation Comments

6. Primary Outcome

Title	Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3
Description	5-point scale (0=no visualization of lesion internal morphology (LIM) [lesion not identified in image, not visible]; 1=poor visualization of LIM [insufficiently depicted, intralesional features poorly identified]; 2=moderate visualization of LIM [not completely depicted, some intralesional features visible]; 3=good visualization of LIM [completely depicted, intralesional features adequately identified]; 4=excellent visualization of LIM [optimally depicted, intralesional features clearly identified and characterized]) paired assessment to compare the difference between pre to pre+postdose
Time Frame	pre-dose to immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	131
Predose	1.4 (1.06)
Pre+Postdose	2.0 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.4 to 0.8
	Parameter Dispersion	Type: Standard Deviation; Value: 1.20
	Estimation Comments

7. Primary Outcome

Title	Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1
Description	5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose
Time Frame	pre-dose and immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	148
Predose	1.8 (1.16)
Pre+Postdose	3.0 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.5
	Parameter Dispersion	Type: Standard Deviation; Value: 1.57
	Estimation Comments

8. Primary Outcome

Title	Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2
Description	5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose
Time Frame	pre-dose to immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	135
Predose	2.0 (1.20)
Pre+Postdose	3.2 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.4
	Parameter Dispersion	Type: Standard Deviation; Value: 1.49
	Estimation Comments

9. Primary Outcome

Title	Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3
Description	5-point scale (0=no lesion CE [lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue]; 1=poor lesion CE [diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size]; 2=moderate lesion CE [diff. in SI fair, lesion identified, not possible to evaluate/measure size]; 3=good lesion CE [diff. in SI adequate, lesion identified, size evaluated/measured]; 4=excellent lesion CE [diff. in SI marked, lesion identified, size measured]) paired assessment to compare the diff. between pre to pre+postdose
Time Frame	pre-dose to immediately postdose

Outcome Measure Data

Analysis Population Description

Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants.

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Measure Lesions	131
Predose	1.4 (0.96)
Pre+Postdose	2.2 (1.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gadobenate Dimeglumine
	Comments	Paired t-test to compare change from pre to pre+postdose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	H0: udiff = 0; Ha: udiff not = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.1
	Parameter Dispersion	Type: Standard Deviation; Value: 1.54
	Estimation Comments

10. Primary Outcome

Title	The Number of Patients Administered MultiHance (Gadobenate Dimeglumine) Reporting Adverse Events
Time Frame	up to 72 hours post dose

Outcome Measure Data

Analysis Population Description

Included all dosed patients (safety population).

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
Measure Participants	92
Number [Participants]	8 8.7%

Adverse Events

Arm/Group Title	Gadobenate Dimeglumine
Arm/Group Description	Contrast Agent, 0.10 mmol/kg injection
All Cause Mortality
	Gadobenate Dimeglumine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gadobenate Dimeglumine
	Affected / at Risk (%)	# Events
Total	0/92 (0%)
Other (Not Including Serious) Adverse Events
	Gadobenate Dimeglumine
	Affected / at Risk (%)	# Events
Total	8/92 (8.7%)
Eye disorders
Eyelid oedema	1/92 (1.1%)	1
Gastrointestinal disorders
Abdominal discomfort	1/92 (1.1%)	1
Constipation	1/92 (1.1%)	1
Vomiting	1/92 (1.1%)	1
Infections and infestations
Otitis media	1/92 (1.1%)	1
Nervous system disorders
Headache	2/92 (2.2%)	2
Somnolence	1/92 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/92 (1.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The results of the study may be presented during scientific symposia or published in a scientific journal only after review by Bracco in accordance with the guidelines set forth in the applicable publication or financial agreement.