Trial Outcomes & Findings for DOTAREM Pharmacokinetics and Safety Study in Pediatric Subjects Aged < 2 Years (NCT NCT02411201)
NCT ID: NCT02411201
Last Updated: 2017-03-09
Results Overview
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.
COMPLETED
PHASE4
51 participants
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
2017-03-09
Participant Flow
A total of 51 children aged less than 2 years were recruited in 4 countries: Austria, France, Hungary and Poland.
Participant milestones
| Measure |
DOTAREM
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
|---|---|
|
Overall Study
STARTED
|
51
|
|
Overall Study
COMPLETED
|
45
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
DOTAREM
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Age group completed
|
2
|
Baseline Characteristics
DOTAREM Pharmacokinetics and Safety Study in Pediatric Subjects Aged < 2 Years
Baseline characteristics by cohort
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
|---|---|
|
Age, Continuous
|
9.9 months
STANDARD_DEVIATION 7.4 • n=39 Participants
|
|
Age, Customized
<1 month
|
5 Participants
n=39 Participants
|
|
Age, Customized
1 to 3 months
|
9 Participants
n=39 Participants
|
|
Age, Customized
>3 months to <24 months
|
31 Participants
n=39 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=39 Participants
|
|
Region of Enrollment
Austria
|
3 participants
n=39 Participants
|
|
Region of Enrollment
Hungary
|
9 participants
n=39 Participants
|
|
Region of Enrollment
Poland
|
29 participants
n=39 Participants
|
|
Region of Enrollment
France
|
4 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 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-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
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.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Area Under the Curve of DOTAREM in Plasma
|
1591.1 hour.µmol/L
Interval 981.43 to 2841.0
|
—
|
PRIMARY outcome
Timeframe: 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-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
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.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Rate Constant of the Terminal Phase of DOTAREM
|
0.5117 hour-1
Interval 0.2288 to 0.7824
|
—
|
PRIMARY outcome
Timeframe: 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-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
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.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Terminal Elimination Half-life of DOTAREM From Plasma
|
1.3545 hour
Interval 0.8859 to 3.0291
|
—
|
PRIMARY outcome
Timeframe: 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-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
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.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Total Clearance of DOTAREM From Plasma
|
0.0602 L/hour per kg
Interval 0.0352 to 0.1019
|
—
|
PRIMARY outcome
Timeframe: 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-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
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.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Volume of Distribution of DOTAREM at Steady State
|
0.0473 L/kg
Interval 0.0273 to 0.1597
|
—
|
SECONDARY outcome
Timeframe: at 10 and 20 min post-injectionPopulation: Among the 45 subjects who received one injection of DOTAREM, all had at least one blood sample available for pharmacokinetics.
Pharmacokinetics interpretation was performed using a pharmacokinetic population modelling approach. DOTAREM concentrations in plasma were analyzed using a validated LC-MS/MS method.
Outcome measures
| Measure |
DOTAREM
n=45 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
Simulated Plasma Concentration of DOTAREM
Simulated concentration at 10 min
|
320.92 µmol/L
Interval 45.223 to 2857.0
|
—
|
|
Simulated Plasma Concentration of DOTAREM
Simulated concentration at 20 min
|
275.67 µmol/L
Interval 47.048 to 1565.1
|
—
|
SECONDARY outcome
Timeframe: Pre-injection and post-injection (estimated between 5 and 20 minutes after injection)Population: Lesion visualization was evaluated in 28 subjects who underwent contrast-enhanced MRI for central nervous system indication.
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)
Outcome measures
| Measure |
DOTAREM
n=28 Participants
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
Pre- + Post-contrast
n=28 Participants
Lesion visualization was assessed after DOTAREM injection
|
|---|---|---|
|
MRI Lesion Visualization at Subject Level
Sum of scores of lesion border delineation
|
4.3 units on a scale
Standard Deviation 3.7
|
5.1 units on a scale
Standard Deviation 4.0
|
|
MRI Lesion Visualization at Subject Level
Sum of scores of internal morphology
|
4.3 units on a scale
Standard Deviation 3.9
|
5.2 units on a scale
Standard Deviation 4.3
|
|
MRI Lesion Visualization at Subject Level
Sum of scores of contrast enhancement
|
1.9 units on a scale
Standard Deviation 1.5
|
5.0 units on a scale
Standard Deviation 4.5
|
Adverse Events
DOTAREM
Serious adverse events
| Measure |
DOTAREM
n=45 participants at risk
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
General disorders
Pyrexia
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
Other adverse events
| Measure |
DOTAREM
n=45 participants at risk
Subjects receiving a single intravenous injection of 0.1 mmol/kg body weight of DOTAREM
|
|---|---|
|
General disorders
Pyrexia
|
11.1%
5/45 • Number of events 5 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
General disorders
Device difficult to use
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
General disorders
Fatigue
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Bronchitis
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Infection
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Nasopharyngitis
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Rhinitis
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Tonsillitis
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Infections and infestations
Urinary tract infection
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Gastrointestinal disorders
Diarrhoea
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.4%
2/45 • Number of events 2 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Nervous system disorders
Tremor
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
|
Gastrointestinal disorders
Nausea
|
2.2%
1/45 • Number of events 1 • Adverse Events were collected from informed consent signature to the end of the study (7+/-1 day after DOTAREM administration)
|
Additional Information
Corinne Dubourdieu, PharmD, Head of Clinical Projects and Medical Writing
Guerbet
Results disclosure agreements
- Principal investigator is a sponsor employee All written or oral papers and publications must have the joint agreement of the investigator and Guerbet. The Investigator shall not use the sponsor's name in any publication without the prior permission of Guerbet. Each investigator agrees not to publish/present the evaluation of the main criterion involving only the patients he/she has included. Any abstract project will be first submitted to Guerbet at least 10 working days before submission to the congress scientific committee.
- Publication restrictions are in place
Restriction type: OTHER