Clinical Trial Results:
Open-label, Single-arm, Multi-center, Pharmacokinetic, Safety and Tolerability Study of Levetiracetam Intravenous Infusion in Children (4 - 16 Years Old) With Epilepsy
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Summary
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EudraCT number |
2006-005722-23 |
Trial protocol |
BE DE FR |
Global end of trial date |
02 Feb 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jun 2016
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First version publication date |
12 Jul 2015
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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 |
N01274
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00535392 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB Pharma S.A.
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Sponsor organisation address |
B-1420 Braine-l’Alleud, Brussels, Belgium, B-1070
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.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 |
24 Mar 2010
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Feb 2010
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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 the safety and tolerability of the Levetiracetam IV 15-minute infusion administered every 12 hours, either as adjunctive treatment or monotherapy in children (4 to 16 years old) with epilepsy (except status epilepticus), either after switching from the equivalent LEV oral dose administration or as a new antiepileptic treatment.
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Protection of trial subjects |
Adequate information was provided to the subject’s parents/legally acceptable representative in both oral and written form and consent was obtained from the parents/legally acceptable representative in writing prior to performance of any study specific procedure. In addition, it was recommended that the subject’s assent was also obtained, according to the child’s age/competence and the IEC/IRB requirements. The content and process of obtaining informed consent was in accordance with all applicable regulatory and IEC/IRB requirements.
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
10 Sep 2007
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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 |
France: 4
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Turkey: 6
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Country: Number of subjects enrolled |
Mexico: 10
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
33
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EEA total number of subjects |
10
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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) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
23
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Adolescents (12-17 years) |
10
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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 |
Subjects were recruited from sites in the United States, Belgium, Germany, France, Mexico, and Turkey. The study began in September 2007 and continued until February 2010, with the last subject's visit occurring in February of 2010. | ||||||
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Pre-assignment
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Screening details |
The Intent-to-Treat (ITT) population was used for results posting. The ITT consists of all subjects who received at least one dose of study medication. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Levetiracetam | ||||||
Arm description |
Intravenous 100 mg/mL, twice a day, maximum of 4 days. Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Levetiracetam tablets
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Investigational medicinal product code |
LEV Tablets
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Other name |
Keppra
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects on oral Levetiracetam at study entry received the same intravenous (IV) dosage (mg-for-mg) to their oral dose.
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Investigational medicinal product name |
Levetiracetam injection
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Investigational medicinal product code |
LEV Injection
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Other name |
Keppra
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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 |
100 mg/mL, twice a day, maximum of 4 days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Levetiracetam
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Reporting group description |
Intravenous 100 mg/mL, twice a day, maximum of 4 days. Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily). | ||
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End point title |
Number of subjects reporting at least 1 Treatment-Emergent Adverse Event (TEAE) during the treatment period (up to 4 days) [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Treatment period (up to 4 days)
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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: The primary objective was to evaluate the safety and tolerability of the LEV IV 15-minute infusion administered every 12 hours, either as adjunctive treatment or monotherapy in children with epilepsy, either after switching from the equivalent LEV oral dose administration or as a new antiepileptic treatment. The safety profile of levocetirizine was summarized descriptively across several safety variables. Therefore, no inferential statistics were performed in this safety study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects who received high-dose levetiracetam intravenous (LEV IV) (more than 40 mg/kg/day) during the treatment period (up to 4 days) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Treatment period (up to 4 days)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of consecutive levetiracetam intravenous (LEV IV) doses received | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Treatment period (up to 4 days)
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 4 days.
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Adverse event reporting additional description |
Treatment-emergent Adverse Events represents the Intent-to-Treat population (ITT), which consists of all subjects who received at least one dose of study medication.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.0
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Reporting groups
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Reporting group title |
Levetiracetam
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Reporting group description |
Intravenous 100 mg/mL, twice a day, maximum of 4 days Subjects on oral levetiracetam at study entry receive the same intravenous (IV) dosage (mg-for-mg) to their oral dose. Dosage for subjects not on levetiracetam at study entry was based on weight: if <50 kg, the dose was 20 mg/kg/day (10 mg/kg/day twice daily); if weight ≥ 50 kg, the dose of levetiracetam intravenous (LEV IV) was 1000 mg/day (500 mg twice daily). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 May 2007 |
Clarification of the procedure for the administration of Levetiracetam (LEV) and of the number of mandatory infusion days. |
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01 Jun 2007 |
Allowed for the adjustment of the LEV dose for subjects with moderate renal insufficiency, based on their CLCR value (compliance with French Competent Authorities). |
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04 Apr 2008 |
Clarified the exclusion criterion for clinically significant acute or chronic illness and deleted the exclusion criteria for intake of 2 or more concomitant AEDs as well as vigabatrine.
Revised the schedule of PK assessment. The predose time point was replaced by a time point at 3 to 10 minutes after the start of the infusion.
Some logistical aspects of the study procedures were revised in order to facilitate the recruitment of subjects. |
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18 Sep 2008 |
Clarified the objectives following the 16 May 2008 teleconference with the FDA, confirming that the main goal of the study was safety and tolerability of the use of LEV IV in pediatrics, with a lesser emphasis on PK.
This amendment also provided for the addition of FDA requests:
- Approximately one half of the subjects exposed to at least 3 consecutive LEV IV doses
- At least one third of the subjects should be in the high-dose range (≥40mg/kg/day)
Additionally, this amendment provided an addition of an exclusion criterion: “The subject presents current depressive symptoms, current suicidal ideation and/or behavior.” |
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12 Nov 2009 |
Clarified the use of local laboratory results for the evaluation of subjects’ eligibility, and updated study team members’ information. |
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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 | |||
