Clinical Trial Results:
DOTAREM® Pharmacokinetics, Safety and Efficacy Study in Pediatric
Subjects Aged <2 Years (Term Newborn Infants to Toddlers 23 Months of Age Inclusive)
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Summary
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EudraCT number |
2013-003215-21 |
Trial protocol |
FR HU AT |
Global end of trial date |
19 Oct 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Jul 2016
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First version publication date |
16 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DGD-44-063
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02411201 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND: 65.041 | ||
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Sponsors
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Sponsor organisation name |
GUERBET
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Sponsor organisation address |
BP 57400, ROISSY CDG Cedex, France, 95943
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Public contact |
Corinne DUBOURDIEU, Head of Clinical Projects , GUERBET, 0033 145915000, corinne.dubourdieu@guerbet-group.com
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Scientific contact |
Corinne DUBOURDIEU, Head of Clinical Projects , GUERBET, 0033 145915000, corinne.dubourdieu@guerbet-group.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Dec 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Oct 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate pharmacokinetics profile in plasma of DOTAREM following
single intravenous injection in pediatric subjects aged up to 23 months
(inclusive)
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Protection of trial subjects |
A PK population approach with sparse blood sampling was used to minimize the clinical burden to children.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Mar 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 32
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Country: Number of subjects enrolled |
Austria: 3
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Country: Number of subjects enrolled |
France: 5
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Country: Number of subjects enrolled |
Hungary: 11
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Worldwide total number of subjects |
51
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EEA total number of subjects |
51
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
5
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Infants and toddlers (28 days-23 months) |
46
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
- | ||||||
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Pre-assignment period milestones
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Number of subjects started |
51 | ||||||
Number of subjects completed |
45 | ||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 2 | ||||||
Reason: Number of subjects |
Adverse event, non-fatal: 2 | ||||||
Reason: Number of subjects |
Age group completed: 2 | ||||||
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Period 1
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Period 1 title |
overall period
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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DOTAREM | ||||||
Arm description |
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Arm type |
Experimental | ||||||
Investigational medicinal product name |
DOTAREM
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
0.1 mmol/kg BW (0.2 ml/kg BW) in a single intravenous injection at 1-2 ml/s
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 51 subjects were enrolled. Among them 45 subjects received IMP. 6 subjects did not reach the baseline period due to non-completion of the pre-assignment period; reasons are reported. Baseline period includes subjects who received IMP only. |
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Baseline characteristics reporting groups
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Reporting group title |
overall period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DOTAREM
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Reporting group description |
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End point title |
Terminal elimination half life [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Blood sampling done 3 times: between 10 min to 60 min, between 2h to 4h and between 6h to 8h post-injection
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis for this endpoint. Descriptive statistics only for PK endpoints |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the curve [2] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Blood sampling done 3 times: between 10 min to 60 min, between 2h to 4h and between 6h to 8h post-injection
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis for this endpoint. Descriptive statistics only for PK endpoints |
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End point title |
Clearance [3] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Blood sampling done 3 times: between 10 min to 60 min, between 2h to 4h and between 6h to 8h post-injection
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis for this endpoint. Descriptive statistics only for PK endpoints |
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of distribution at steady state [4] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Blood sampling done 3 times: between 10 min to 60 min, between 2h to 4h and between 6h to 8h post-injection
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis for this endpoint. Descriptive statistics only for PK endpoints |
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Adverse events information
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Timeframe for reporting adverse events |
From informed consent signature untill end of study (7+/- 1 days after IMP administration)
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Adverse event reporting additional description |
Adverse events occuring after IMP administration are listed below.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Safety set
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Sep 2014 |
Change the study phase from phase I to phase IV: the Investigational Medicinal Product (DOTAREM®) was used in the study in indications and population approved in the countries where the study was conducted. The reference document was the local Summary of Product Characteristics.
Add clarification on the collection of blood for PK
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24 Mar 2015 |
Removal of coordinating investigator due to the death of Pr Guy Sebag.
Recruitment period extended to Q4 2015 and enlarged to 20 sites worldwide.
Inclusion criterion related to the normal renal function was clarified.
Non-inclusion criterion related to severe liver disease was clarified.
Non-inclusion criterion related to the previous participation to a clinical study was reduced to 7 days.
Non-inclusion criteria related to the concomitant participation to a clinical study was clarified.
The group of age was collected instead of date of birth according to local regulations in some countries.
The definition of overdose was added to follow an update in Good Vigilance Practice. Rules for rounding the dose administered were then removed. Adverse event definition, including overdose, was updated.
The “safety follow-up phone call” at visit 4 was changed in a “safety follow-up contact” which allowed different ways to monitor the subject’s safety at day 7 +/-1.
Clarifications were made on the use of local laboratory data to validate the normal renal function at inclusion time.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
