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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00937391
First received: July 10, 2009
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Magnetic Resonance Imaging
Drug: Gadopentetate dimeglumine (Magnevist, BAY86-6661)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of Participants With Diagnostic Adequacy - Open-label Clinical Investigators (Per Protocol Set) [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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) [ Time Frame: 20 to 45 min and 4 to 8 hours post injection ] [ Designated as safety issue: No ]
    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) [ Time Frame: 20 to 45 min and 4 to 8 hours post injection ] [ Designated as safety issue: No ]
    CL/BW = total clearance normalized by BW

  • PK Analysis - Volume of Distribution at Steady State (Vss) [ Time Frame: 20 to 45 min and 4 to 8 hours post injection ] [ Designated as safety issue: No ]
    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) [ Time Frame: 20 to 45 min and 4 to 8 hours post injection ] [ Designated as safety issue: No ]
    Vss/BW = volume of distribution at steady state normalized by body weight

  • PK Analysis - Area Under the Drug Concentration-time Curve (AUC) [ Time Frame: Samples taken 20 to 45 min and 4 to 8 hours post injection. AUC calculated from time of injection to infinity. ] [ Designated as safety issue: No ]
    AUC = Area under the drug concentration-time curve from administration to infinity

  • PK Analysis - t 1/2 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    t 1/2 = termination elimination half-life calculated from the area under the drug concentration-time curve from administration to infinity


Secondary Outcome Measures:
  • Number of Participants With Number of Lesions Detected - Stage 1 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 Specific Change in the Diagnosis From Unenhanced to Combined Images - Stage 2 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 1 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 Diagnostic Confidence - Stage 2 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes before injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes before injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 5 minutes after injection ] [ Designated as safety issue: No ]
    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


Enrollment: 54
Study Start Date: January 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)).

Detailed Description:

Safety issues are addressed in the AE section

  Eligibility

Ages Eligible for Study:   2 Months to 23 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00937391

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

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00937391     History of Changes
Other Study ID Numbers: 91784, 2009-014584-39, 312046
Study First Received: July 10, 2009
Results First Received: September 8, 2011
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
MRI agents
Magnevist

Additional relevant MeSH terms:
Gadolinium DTPA
Gadobenic acid
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014