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

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

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

Study Overview

• Status: Completed
• Conditions: Magnetic Resonance Imaging
• Intervention / Treatment: Drug: Gadopentetate dimeglumine (Magnevist, BAY86-6661)

Detailed Description

Safety issues are addressed in the AE section

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
  • Thüringen
    • Jena, Thüringen, Germany, 07740
• United States
  • California
    • San Diego, California, United States, 92123
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Illinois
    • Chicago, Illinois, United States, 60614
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Missouri
    • Kansas City, Missouri, United States, 64108-9898
    • St. Louis, Missouri, United States, 63110
  • Ohio
    • Akron, Ohio, United States, 44308
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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)).

Drug: 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)).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: July 10, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: October 19, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Magnevist; MRI agents
• Other Study ID Numbers: 91784; 2009-013081-17 (EudraCT Number); 312046 (Other Identifier: company internal)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No