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

Phase 3

Completed

Conditions: Magnetic Resonance Imaging

Interventions: Drug: Gadopentetate dimeglumine (Magnevist, BAY86-6661)

Registration Number: NCT00937391

Lead Sponsor: Bayer

Brief Summary: 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: Safety issues are addressed in the AE section

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gadopentetate dimeglumine (Magnevist, BAY86-6661)	Gadopentetate dimeglumine (Magnevist, BAY86-6661)	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)).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Diagnostic Adequacy - Open-label Clinical Investigators (Per Protocol Set)	Within 5 minutes after injection	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.
Dose Determined by Blinded Readers to be Superior for Diagnosis	Within 5 minutes after injection	Dose superiority was a calculation based upon the Blinder Readers' assessment of 4 visualization parameters
Paired-dose Comparison of Number of Participants With Dose Superiority Determined for 4 Lesion Visualization Variables - Blinded Readers	Within 5 minutes after injection	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.
PK Analysis - Total Clearance (CL)	20 to 45 min and 4 to 8 hours post injection	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.
PK Analysis - Total Clearance (CL)/Body Weight (BW)	20 to 45 min and 4 to 8 hours post injection	CL/BW = total clearance normalized by BW
PK Analysis - Volume of Distribution at Steady State (Vss)	20 to 45 min and 4 to 8 hours post injection	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.
PK Analysis - Volume of Distribution at Steady State (Vss) /Body Weight (BW)	20 to 45 min and 4 to 8 hours post injection	Vss/BW = volume of distribution at steady state normalized by body weight
PK Analysis - Area Under the Drug Concentration-time Curve (AUC)	Samples taken 20 to 45 min and 4 to 8 hours post injection. AUC calculated from time of injection to infinity.	AUC = Area under the drug concentration-time curve from administration to infinity
PK Analysis - t 1/2	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	t 1/2 = termination elimination half-life calculated from the area under the drug concentration-time curve from administration to infinity

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Number of Lesions Detected - Stage 1	Within 5 minutes after injection	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.
Number of Participants With Number of Lesions Detected - Stage 2	Within 5 minutes after injection	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.
Number of Participants With Quality of Lesion Visualization - Stage 1	Within 5 minutes after injection	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)
Number of Participants With Quality of Lesion Visualization - Stage 2	Within 5 minutes after injection	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)
Number of Participants With Quality of Border Delineation - Stage 1	Within 5 minutes after injection	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
Number of Participants With Quality of Border Delineation - Stage 2	Within 5 minutes after injection	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
Most Frequent Diagnostic Findings With Unenhanced Images - Stage 1	Within 5 minutes after injection	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
Most Frequent Diagnostic Findings With Unenhanced Images - Stage 2	Within 5 minutes after injection	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
Overall Number of Participants With Change in Diagnosis From Unenhanced to Combined Images - Stage 1	Within 5 minutes after injection	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
Overall Number of Participants With Change in Diagnosis From Unenhanced to Combined Images - Stage 2	Within 5 minutes after injection	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
Number of Participants With Specific Change in the Diagnosis From Unenhanced to Combined Images - Stage 1	Within 5 minutes after injection	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.
Number of Participants With Diagnostic Confidence - Stage 1	Within 5 minutes after injection	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
Number of Participants With Specific Change in the Diagnosis From Unenhanced to Combined Images - Stage 2	Within 5 minutes after injection	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
Number of Participants With Diagnostic Confidence - Stage 2	Within 5 minutes after injection	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
Management Based on Unenhanced Images - Stage 1	Within 5 minutes before injection	For Stage 1 based on unenhanced images, the recommended management is presented as determined by the open-label Clinical Investigators.
Management Based on Unenhanced Images - Stage 2	Within 5 minutes before injection	For Stage 2 based on unenhanced images, the recommended management is presented as determined by the open-label Clinical Investigators.
Overall Number of Participants With Change in Management From Unenhanced to Combined Images - Stage 1	Within 5 minutes after injection	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.
Overall Number of Participants With Change in Management From Unenhanced to Combined Images - Stage 2	Within 5 minutes after injection	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.
Number of Participants With Specific Change in Management From Unenhanced to Combined Images - Stage 1	Within 5 minutes after injection	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
Number of Participants With Specific Change in Management From Unenhanced to Combined Images - Stage 2	Within 5 minutes after injection	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