Contrast-enhanced MRI in Children 2 Months to <2 Years

Study Overview
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Brief Summary
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The purpose of this study is to determine pharmacokinetics, safety and efficacy of Magnevist in children 2 months to < 2 years of age

Detailed Description
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Safety issues are addressed in the AE section

Official Title
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Open-label, Multi-center, Two-stage, Age Stratified, Pharmacokinetic, Safety, and Efficacy Study in Children 2 Months to < 2 Years of Age Undergoing Magnevist Injection Enhanced MRI

Conditions
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Magnetic Resonance Imaging

Intervention / Treatment
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* Drug: Gadopentetate dimeglumine (Magnevist, BAY86-6661)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 2 months to < 2 years (23 months) Participants (male/female) who are scheduled to undergo gadolinium-enhanced MRI Able to comply with the study procedures Exclusion Criteria: Clinical unstable participants (eg, intensive care unit) Renal Insufficiency Participants undergoing chemotherapy </= 48 hours prior to and up to 24 hours after the administration of Magnevist.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gadopentetate dimeglumine (Magnevist, BAY86-6661)<br>For stage 1: Participants received an IV injection of 0.05 mmol/kg Body Weight (BW) (0.1 mL/kg BW) Magnevist. Upon completion of the MR imaging, the participants received another injection of 0.05 mmol/kg for a total cumulative dose of 0.1 mmol/kg BW (0.2 mL/kg BW). For stage 2: Participants received the optimal efficacious dose established in Stage 1 as a single IV injection of Magnevist Injection (0.1 mmol/kg BW (0.2 mL/kg BW)). | Drug: Gadopentetate dimeglumine (Magnevist, BAY86-6661)<br>* For stage 1: Participants received an IV injection of 0.05 mmol/kg Body Weight (BW) (0.1 mL/kg BW) Magnevist. Upon completion of the MR imaging, the participants received another injection of 0.05 mmol/kg for a total cumulative dose of 0.1 mmol/kg BW (0.2 mL/kg BW). For stage 2: Participants received the optimal efficacious dose established in Stage 1 as a single IV injection of Magnevist Injection (0.1 mmol/kg BW (0.2 mL/kg BW)).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Diagnostic Adequacy - Open-label Clinical Investigators (Per Protocol Set) | A clinical judgment by the open-label Clinical Investigators (CIs) as to whether (yes) or not (no) the CI could make a diagnosis from the image. | Within 5 minutes after injection | 
| Dose Determined by Blinded Readers to be Superior for Diagnosis | Dose superiority was a calculation based upon the Blinder Readers' assessment of 4 visualization parameters | Within 5 minutes after injection | 
| Paired-dose Comparison of Number of Participants With Dose Superiority Determined for 4 Lesion Visualization Variables - Blinded Readers | For each participant, the Blinded Reader indicated which dose had better contrast enhancement, better border delineation, clearer internal morphology, and provided more diagnostic information. The dose chosen for 3 or 4 of these variables was the selected dose for that Reader and participant. If each dose was superior on 2 variables, the dose which provided more diagnostic information was selected for that participant. The dose selected for the majority of participants was the dose selected by that Reader; if chosen by 2 or 3 Readers, it was the selected dose. | Within 5 minutes after injection | 
| PK Analysis - Total Clearance (CL) | Total clearance is the fraction of the volume of distribution (Vd) which is completely purified per unit of time and depends also on the plasma half-life of the drug. | 20 to 45 min and 4 to 8 hours post injection | 
| PK Analysis - Total Clearance (CL)/Body Weight (BW) | CL/BW = total clearance normalized by BW | 20 to 45 min and 4 to 8 hours post injection | 
| PK Analysis - Volume of Distribution at Steady State (Vss) | Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state. | 20 to 45 min and 4 to 8 hours post injection | 
| PK Analysis - Volume of Distribution at Steady State (Vss) /Body Weight (BW) | Vss/BW = volume of distribution at steady state normalized by body weight | 20 to 45 min and 4 to 8 hours post injection | 
| PK Analysis - Area Under the Drug Concentration-time Curve (AUC) | AUC = Area under the drug concentration-time curve from administration to infinity | Samples taken 20 to 45 min and 4 to 8 hours post injection. AUC calculated from time of injection to infinity. | 
| PK Analysis - t 1/2 | t 1/2 = termination elimination half-life calculated from the area under the drug concentration-time curve from administration to infinity | Samples taken at 20 to 45 min and at 4 to 8 hours post injection; t 1/2 calculated from area under the drug concentration-time curve from administration to infinity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Number of Lesions Detected - Stage 1 | BR = blinded reader; CI = clinical investigator; unenh. image = unenhanced image; comb. image= combined unenhanced and enhanced image. The Blinded Readers and the open-label Clinical Investigators determined the number of participants with 0, 1, 2, and 3 or more lesions. | Within 5 minutes after injection | 
| Number of Participants With Number of Lesions Detected - Stage 2 | BR = blinded reader; CI = clinical investigator; unenh. image = unenhanced image; comb. image= combined unenhanced and enhanced image. The Blinded Readers and the open-label Clinical Investigators determined the number of participants with 0, 1, 2, and 3 or more lesions. | Within 5 minutes after injection | 
| Number of Participants With Quality of Lesion Visualization - Stage 1 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the quality of lesion visualization with the unenhanced and the combined image sets based on a 3-point scale (1=excellent - lesion clearly seen and diagnosis possible; 2=fair but adequate - most of lesion seen and diagnosis possible; and 3=poor - lesion barely seen and diagnosis not possible) | Within 5 minutes after injection | 
| Number of Participants With Quality of Lesion Visualization - Stage 2 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the quality of lesion visualization with the unenhanced and the combined image sets based on a 3-point scale (1=excellent - lesion clearly seen and diagnosis possible; 2=fair but adequate - most of lesion seen and diagnosis possible; and 3=poor - lesion barely seen and diagnosis not possible) | Within 5 minutes after injection | 
| Number of Participants With Quality of Border Delineation - Stage 1 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the quality of border delineation based on a 3-point scale (1=excellent - border completely delineated; 2=fair but adequate - some of the border is delineated; and 3=poor - entire or almost the entire border is not delineated) by image set | Within 5 minutes after injection | 
| Number of Participants With Quality of Border Delineation - Stage 2 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the quality of border delineation based on a 3-point scale (1=excellent - border completely delineated; 2=fair but adequate - some of the border is delineated; and 3=poor - entire or almost the entire border is not delineated) by image set | Within 5 minutes after injection | 
| Most Frequent Diagnostic Findings With Unenhanced Images - Stage 1 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the most frequent diagnostic findings with the unenhanced images | Within 5 minutes after injection | 
| Most Frequent Diagnostic Findings With Unenhanced Images - Stage 2 | BR = blinded reader; CI = clinical investigator. The Blinded Readers and the open-label Clinical Investigators determined the most frequent diagnostic findings with the unenhanced images | Within 5 minutes after injection | 
| Overall Number of Participants With Change in Diagnosis From Unenhanced to Combined Images - Stage 1 | The Blinded Readers and the open-label Clinical Investigators determined the number of participants with a change in diagnosis from unenhanced to combined images. BR = blinded reader; CI = clinical investigator | Within 5 minutes after injection | 
| Overall Number of Participants With Change in Diagnosis From Unenhanced to Combined Images - Stage 2 | The Blinded Readers and the open-label Clinical Investigators determined the number of participants with a change in diagnosis from unenhanced to combined images. BR = blinded reader; CI = clinical investigator | Within 5 minutes after injection | 
| Number of Participants With Specific Change in the Diagnosis From Unenhanced to Combined Images - Stage 1 | Those participants for whom the diagnosis changed for at least 1 Blinded Reader from unenhanced to combined images are presented for Stage 1. For completeness, the corresponding data for these participants are presented for the open-label Clinical Investigators. BR=Blinded Reader; CI=Clinical Investigator. | Within 5 minutes after injection | 
| Number of Participants With Specific Change in the Diagnosis From Unenhanced to Combined Images - Stage 2 | Those participants for whom the diagnosis changed for at least 1 Blinded Reader from unenhanced to combined images are presented for Stage 2. For completeness, the corresponding data for these participants are presented for the open-label Clinical Investigators. BR=Blinded Reader; CI=Clinical Investigator | Within 5 minutes after injection | 
| Number of Participants With Diagnostic Confidence - Stage 1 | The overall diagnostic confidence of the Blinded Readers and the open-label Clinical Investigators was indicated on a 3-point scale: 1=not confident; 2=confident; and 3=very confident. BR=Blinder Reader; CI=Clinical Investigator | Within 5 minutes after injection | 
| Number of Participants With Diagnostic Confidence - Stage 2 | The overall diagnostic confidence of the Blinded Readers and the open-label Clinical Investigators was indicated on a 3-point scale: 1=not confident; 2=confident; and 3=very confident. BR=Blinder Reader; CI=Clinical Investigator | Within 5 minutes after injection | 
| Management Based on Unenhanced Images - Stage 1 | For Stage 1 based on unenhanced images, the recommended management is presented as determined by the open-label Clinical Investigators. | Within 5 minutes before injection | 
| Management Based on Unenhanced Images - Stage 2 | For Stage 2 based on unenhanced images, the recommended management is presented as determined by the open-label Clinical Investigators. | Within 5 minutes before injection | 
| Overall Number of Participants With Change in Management From Unenhanced to Combined Images - Stage 1 | For Stage 1, the number of participants for whom the recommended management of the open-label Clinical Investigators changed from unenhanced to combined images is presented for both doses. | Within 5 minutes after injection | 
| Overall Number of Participants With Change in Management From Unenhanced to Combined Images - Stage 2 | For Stage 2, the number of participants for whom the recommended management of the open-label Clinical Investigators changed from unenhanced to combined images is presented for the optimal efficacious dose determined in Stage 1. | Within 5 minutes after injection | 
| Number of Participants With Specific Change in Management From Unenhanced to Combined Images - Stage 1 | The actual change in management from unenhanced to combined images recommended by the open-label Clinical Investigators is presented for both doses in Stage 1 | Within 5 minutes after injection | 
| Number of Participants With Specific Change in Management From Unenhanced to Combined Images - Stage 2 | The actual change in management from unenhanced to combined images recommended by the open-label Clinical Investigators is presented in Stage 2 for the optimal efficacious dose determined in Stage 1 | Within 5 minutes after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI agents, Magnevist