Magnetic Resonance ImagingPhase 4NCT02411201

DOTAREM Pharmacokinetics and Safety Study in Pediatric Subjects Aged < 2 Years

A Phase 4 study testing DOTAREM in people with Magnetic Resonance Imaging, run by Guerbet at 9 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The main purpose of the study is to evaluate the pharmacokinetics of DOTAREM® in the body of children aged less than 2 years thanks to several blood samples (3 ml in total) taken following the administration of DOTAREM®. Read more about this study

Who is it for?: Ages Up to 2 years
Conditions the study is for: Magnetic Resonance Imaging
What is being tested?: DOTAREM
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 9 sitesin 4 countries
Study dates: Mar 2015to Oct 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 2 years
All sexes
No healthy volunteers
Child

Who may be able to join

Pediatric subject aged <2 years (term newborn infants to toddlers 23 months of age inclusive). Term is defined as ≥37 weeks of amenorrhea
Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region (e.g. CNS, cardiac) at the dose of 0.1 mmol/kg BW (0.2 mL/kg BW)
Subject with normal renal function for its age, estimated glomerular filtration rate calculated based on the Schwartz formula

Who cannot join

Subject planned for intervention (e.g. surgery) between the screening visit and up to 24 hours after DOTAREM injection
Subject whose preceding or subsequent treatment to DOTAREM injection (e.g., blood loss or receiving blood, treatment with diuretics, etc…) would alter DOTAREM pharmacokinetics parameters
Subject with subsequent planned treatment after DOTAREM injection that would prevent obtaining the required blood samples (e.g., emergency surgery, etc…)
Subject with a history of a bleeding disorder
Subject with severe liver disease (Child's Pugh Classification B or greater or serum direct bilirubin greater than 0.3 mg/dL, age adjusted)
Subject with electrolyte or fluid imbalance that presents undue risk

Show all 12Show fewer

Subject undergoing a change in chemotherapy within 48 hours prior to and up to 24 hours after DOTAREM injection
Subject who received or will receive any other contrast agent within 72 hours prior to DOTAREM injection or up to 24 hours after DOTAREM injection
Subject with contraindication for MRI such as iron metal implants (e.g. aneurysm clips)
Subject with history of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents
Subject having participated within 30 days in a clinical study involving an investigational drug or device
Subject planned to participate simultaneously to another clinical study

Trial locations and contacts

9 sites in 4 countries.

Country

City, postcode or hospital

9 sites in 4 countries

France3 sites

CHU
Bordeaux, 33604
CHRU
Lille, 59037
Hôpital de Hautepierre
Strasbourg, 67098

Other trials in France

Hungary3 sites

Department of Molecular and Neurological Clinical and Research Center
Budapest, 1083
University of Debrecen Medical Center
Debrecen, 4032
Borsod-Abaúj-Zemplén University County Hospital
Miskolc, 3526

Other trials in Hungary

Poland2 sites

Uniwersytecki Szpital Dziecięcy w Lublinie
Lublin, 20093
Instytut Pomnik -Centrum Zdrowia Dziecka
Warsaw, 04730

Other trials in Poland

Austria1 site

Landes-Frauen-und Kinderklinik Linz
Linz, 4020

Other trials in Austria

About this study

Official title: DOTAREM® Pharmacokinetics, Safety and Efficacy Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)

DOTAREM® is a contrast agent commonly used for enhancement of Magnetic Resonance Imaging (MRI) to potentially improve the quality of the images and help the diagnosis. Children aged less than 2 years scheduled to undergo routine gadolinium-enhanced MRI of any body region may take part in the study. In this case they will receive DOTAREM®, a solution injected at the standard dose of 0.2mL/kg (0.1 mmol/kg) of body weight.

Conditions: Magnetic Resonance Imaging
Being tested: DOTAREM

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DOTAREMDrug
Also called gadoterate meglumine
Single intravenous injection of 0.1 mmol/kg body weight

Study groups in NCT02411201
Study group	Role	What they receive
DOTAREM	Experimental	Not described Receives: Drug: DOTAREM

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Curve of DOTAREM in Plasma
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Area under the curve was determined from typical and individual DOTAREM concentration-time profiles.
Measured: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Rate Constant of the Terminal Phase of DOTAREM
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Rate constant of the terminal phase was determined from typical and individual DOTAREM concentration-time profiles.
Measured: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Terminal Elimination Half-life of DOTAREM From Plasma
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Terminal elimination half-life was determined from typical and individual DOTAREM concentration-time profiles.
Measured: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Total Clearance of DOTAREM From Plasma
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Total clearance was determined from typical and individual DOTAREM concentration-time profiles.
Measured: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Volume of Distribution of DOTAREM at Steady State
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Volume of distribution at steady state was determined from typical and individual DOTAREM concentration-time profiles.
Measured: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection

Secondary outcomes (2)

Simulated Plasma Concentration of DOTAREM
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method.
Measured: at 10 and 20 min post-injection
MRI Lesion Visualization at Subject Level
Lesion visualization was assessed on up to five most representative lesions per subject based on scoring of 3 co-endpoints:
- border delineation (based on a 3-point scale where 1=none; 2=moderate and 3=clear and complete)
- internal morphology (based on a 3-point scale where 1=poorly visible; 2=moderately visible and 3=sufficiently visible)
- contrast enhancement (based on a 3-point scale where 1=none; 2=weak and 3=clear and bright)
For each co-endpoint, a sum of scores was calculated at subject level as follows: sum of scores = score of the lesion 1 (+ score of the lesion 2 + score of the lesion 3 + score of the lesion 4 + score of the lesion 5, when applicable)
Measured: Pre-injection and post-injection (estimated between 5 and 20 minutes after injection)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2015Oct 2015

First posted8 Apr 2015 (estimated)
Study startMar 2015
Primary completionOct 2015
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Magnetic Resonance ImagingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02411201
Sponsor's protocol ID: DGD-44-063
Other IDs: 2013-003215-21
Status last verified: Jan 2017
First submitted: 11 Mar 2015
Last updated: 9 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Magnetic Resonance Imaging trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: DOTAREM® Pharmacokinetics, Safety and Efficacy Study in Pediatric Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)
ClinicalTrials.gov ID: NCT02411201
Acronym / sponsor ID: DGD-44-063
Conditions: Magnetic Resonance Imaging
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: GuerbetIndustry (pharma, biotech, devices)
Study start: Mar 2015
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 8 Apr 2015 (estimated)
Results: Posted 9 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
DOTAREM	Experimental	Drug: DOTAREM

Who may qualify

Ages: Up to 2 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Pediatric subject aged <2 years (term newborn infants to toddlers 23 months of age inclusive). Term is defined as ≥37 weeks of amenorrhea
Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region (e.g. CNS, cardiac) at the dose of 0.1 mmol/kg BW (0.2 mL/kg BW)
Subject with normal renal function for its age, estimated glomerular filtration rate calculated based on the Schwartz formula

Key exclusion criteria (12 listed)

Subject planned for intervention (e.g. surgery) between the screening visit and up to 24 hours after DOTAREM injection
Subject whose preceding or subsequent treatment to DOTAREM injection (e.g., blood loss or receiving blood, treatment with diuretics, etc…) would alter DOTAREM pharmacokinetics parameters
Subject with subsequent planned treatment after DOTAREM injection that would prevent obtaining the required blood samples (e.g., emergency surgery, etc…)
Subject with a history of a bleeding disorder
Subject with severe liver disease (Child's Pugh Classification B or greater or serum direct bilirubin greater than 0.3 mg/dL, age adjusted)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DOTAREMAlso: gadoterate meglumineSingle intravenous injection of 0.1 mmol/kg body weight	Drug	DOTAREM

Primary outcome

Area Under the Curve of DOTAREM in Plasma
Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Area under the curve was determined from typical and individual DOTAREM concentration-time profiles.
Rate Constant of the Terminal Phase of DOTAREM
Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Rate constant of the terminal phase was determined from typical and individual DOTAREM concentration-time profiles.
Terminal Elimination Half-life of DOTAREM From Plasma
Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Terminal elimination half-life was determined from typical and individual DOTAREM concentration-time profiles.
Total Clearance of DOTAREM From Plasma
Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Total clearance was determined from typical and individual DOTAREM concentration-time profiles.
Volume of Distribution of DOTAREM at Steady State
Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method. Volume of distribution at steady state was determined from typical and individual DOTAREM concentration-time profiles.

2 secondary outcomes

Simulated Plasma Concentration of DOTAREM
Time frame: at 10 and 20 min post-injection
MRI Lesion Visualization at Subject Level
Time frame: Pre-injection and post-injection (estimated between 5 and 20 minutes after injection)

Results and safety

Results posted to the registry on 9 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DOTAREM	51	45

Primary outcome: Area Under the Curve of DOTAREM in Plasma

Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection. Median (Full Range). Unit: hour.µmol/L

Measure	DOTAREM n = 45
Value	1591.1 (981.43 to 2841)

Population analysed: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.

Primary outcome: Rate Constant of the Terminal Phase of DOTAREM

Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection. Median (Full Range). Unit: hour-1

Measure	DOTAREM n = 45
Value	0.5117 (0.2288 to 0.7824)

Population analysed: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.

Primary outcome: Terminal Elimination Half-life of DOTAREM From Plasma

Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection. Mean (Full Range). Unit: hour

Measure	DOTAREM n = 45
Value	1.3545 (0.8859 to 3.0291)

Population analysed: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.

Primary outcome: Total Clearance of DOTAREM From Plasma

Time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection. Mean (Full Range). Unit: L/hour per kg

Measure	DOTAREM n = 45
Value	0.0602 (0.0352 to 0.1019)

Population analysed: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DOTAREM	1 of 45 (2.2%)	12 of 45 (26.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Project Manager study director

Guerbet

9 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing DOTAREM in people with Magnetic Resonance Imaging, run by Guerbet at 9 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France, Hungary, Poland, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve of DOTAREM in Plasma (time frame: Blood samples were collected during 3 time windows: 15 min to 60 min, 2 hours to 4 hours and 6 hours to 8 hours post-injection). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02411201.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2017.