Gadobutrol Pharmacokinetic and Safety Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)

NCT01544166 | Completed Phase 1 Results

• 2 other identifiers: 917412010-023003-96
• Study Type: interventional
• Target: 44
• Locations: 3 countries
• Sites: 9

Brief Summary

The main purpose of this study is to collect data on the way gadobutrol is taken into, moves around, and is eliminated from, the body of children aged 0 to less than 2 years. The study will also evaluate safety and tolerability, and efficacy of gadobutrol. A maximum total amount of approximately 5 ml of blood will be needed for these analyses which will be drawn within 2-3 days. Gadobutrol is a contrast agent used for enhancement of Magnetic Resonance Imaging (MRI), potentially allowing better visibility of tissues in the body. Children aged under 2 years scheduled for a routine contrast-enhanced MRI examination of any body region may take part in this study, in which case they will receive gadobutrol as contrast agent intravenously at the standard dose of 0.1 mmol/kg (0.1 ml/Kg) of body weight. Only subjects without renal insufficiency of any intensity (i.e. estimated Glomerular Filtration Rate \<80% of age adjusted normal value calculated based on the Schwartz formula) will be included in the trial. The duration of this study as a whole is around 1 year and the total number of children to be enrolled is 50. A child will be expected to take part in the study for around 7 days.

Conditions

Magnetic Resonance Imaging

Keywords

Gadolinium, Pediatrics, MRI, contrast

Outcome Measures

Primary Outcomes (7)

• Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual

  AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC from time 0 (start of injection) to infinity was reported in micromole\*hour per liter (micromole\*h/L).

  Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

• Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual

  Clearance is the volume of the fluid presented to the eliminating organ that is effectively completely cleared of drug per unit time and depends on the rate of elimination. CL of gadobutrol normalized for body weight, was reported in Liter per hour per kilogram (L/(h\*kg).

  Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

• Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual

  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.

  Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

• Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual

  MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.

  Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

• Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual

  Half-life refers to the elimination of the drug, that is, the time it takes for the blood plasma concentration to reach half the concentration. Terminal elimination half-life of gadobutrol from plasma is expressed in hours and is derived from the terminal slope of the concentration versus time curve.

  Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol

• Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)

  Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C20 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.

  20 minutes post-injection

• Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)

  Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C30 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.

  30 minutes post-injection

Secondary Outcomes (33)

• Number of Subjects With Anatomical Area Evaluated

  Images were taken pre-injection and post-injection (within about 15 minutes)

• Number of Subjects With Technical Adequacy for Diagnosis

  Images were taken pre-injection and post-injection (within about 15 minutes)

• Number of Subjects With Technical Adequacy for Diagnosis by Body Region

  Images were taken pre-injection and post-injection (within about 15 minutes)

• Number of Subjects by Overall Contrast Quality

  Images were taken post-injection (within about 15 minutes)

• Number of Subjects by Overall Contrast Quality by Body Region

  Images were taken post-injection (within about 15 minutes)

Other Outcomes (1)

• Number of Subjects With Drug Related Serious and Non- Serious Adverse Events

  From baseline to approximately 7 days after injection

Study Arms (1)

Overall study

EXPERIMENTAL

Drug: Gadobutrol (Gadavist, BAY86-4875)

Interventions

Gadobutrol (Gadavist, BAY86-4875) DRUG

Single intravenous bolus injection of gadobutrol 0.1 mmol/kg BW in term newborns to infants \<2 years of age.

Overall study

Eligibility Criteria

• Age: Up to 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pediatric subjects aged \<2 years (term newborn infants to toddlers 23 months of age inclusive)
• Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region

You may not qualify if:

• Subjects undergoing a change in chemotherapy within 48 hours prior to and up to 24 hours after gadobutrol injection
• Any planned intervention during the study and up to 24 hours after gadobutrol injection (excluding lumbar puncture)
• Subjects who received or will receive any investigational product within 48 hours before gadobutrol injection or during study participation
• Subjects who received or will receive any other contrast agent within 48 hours prior to gadobutrol injection or up to 24 hours after gadobutrol injection
• Subjects with contraindication for MRI such as iron metal implants (e.g. aneurysm clips)
• History of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents
• Subject with renal insufficiency of any intensity, i.e. estimated Glomerular Filtration Rate \<80% of age adjusted normal value calculated based on the Schwartz formula

Sponsors & Collaborators

• Bayer: lead

Study Sites (9)

Unknown Facility

Savannah, Georgia, 31406, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Boston, Massachusetts, 02111, United States

Location

Unknown Facility

Cincinnati, Ohio, 45229, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Edmonton, Alberta, T6G 2B7, Canada

Location

Unknown Facility

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Halle, Saxony-Anhalt, 06097, Germany

Location

Unknown Facility

Jena, Thuringia, 07740, Germany

Location

Related Links

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

MeSH Terms

Interventions

gadobutrol

Limitations and Caveats

Results for Typical PK parameters were provided by the median value of the population together with the min-max range (individual PK). Typical PK parameter as described in study protocol was reflected by the Median PK parameter in the study report.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer HealthCare AG

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2012
• First Posted: March 5, 2012
• Study Start: May 16, 2012
• Primary Completion: November 28, 2013
• Study Completion: November 28, 2013
• Last Updated: December 16, 2020
• Results First Posted: November 26, 2014

Record last verified: 2020-11

Locations

CA (1); DE (3); US (5)