Clinical Trial Results:
Open-label, Single-arm, Multi-center, Pharmacokinetic, Safety and Tolerability Study of Levetiracetam Intravenous Infusion in Children (1 Month- 4 Years Old) With Epilepsy
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Summary
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EudraCT number |
2007-003517-13 |
Trial protocol |
BE DE FR |
Global end of trial date |
11 Mar 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 |
05 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 |
N01275
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00505934 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB Pharma SA
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Sponsor organisation address |
Chemin du Foriest, Braine-l’Alleud, Belgium, B-1420
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 4815 15, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 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 |
15 Jun 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 |
11 Mar 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 |
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 (1 month to <4 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 |
Subjects were hospitalized for the duration of the levetiracetam iv treatment. For the Screening and Final Visit, blood samples were drawn by direct venipuncture using disposable needles. During the treatment period, a catheter may have been used to minimize trauma and speed up sampling. The catheter could have been fitted on the morning of the first day. If not possible, direct venipuncture was performed. EMLA (or other topical anesthetics) could have been used to minimize pain due to puncture or insertion of a catheter. Blood samples must have been taken from another vein than the vein used for the IV infusion.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
16 May 2008
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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 |
United States: 7
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Country: Number of subjects enrolled |
Mexico: 8
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Turkey: 2
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Country: Number of subjects enrolled |
Germany: 1
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Worldwide total number of subjects |
19
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EEA total number of subjects |
2
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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) |
12
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Children (2-11 years) |
7
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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 |
Subjects were recruited from sites in the United States, Belgium, Germany, France, Mexico, and Turkey. The study began in May 2008 and continued until March 2010, with the last subject's visit occurring in March of 2010. | ||||||||||||||
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Pre-assignment
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Screening details |
Of the 23 subjects screened, 19 were enrolled into the study and received levetiracetam IV (LEV IV). Participant Flow refers to the Intent-to-treat (ITT) Population, consisting of all subjects who received at least 1 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 |
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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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 within the following dose range, calculated on the basis of their age and weight: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily); • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily). • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily). | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Levetiracetam
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Investigational medicinal product code |
LEV
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Other name |
Keppra
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
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, calculated on the basis of their age and weight.
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Baseline characteristics 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 within the following dose range, calculated on the basis of their age and weight: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily); • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily). • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 within the following dose range, calculated on the basis of their age and weight: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily); • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily). • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg 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: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only. |
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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 28 mg/kg/day for subjects <6 months; >40 mg/kg/day for subjects ≥6 months) 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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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 within the following dose range, calculated on the basis of their age and weight: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily) to 42 mg/kg/day (21 mg/kg/day twice daily); • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg twice daily) to 60 mg/kg/day (30 mg/kg/day twice daily). For subjects not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dosage corresponded to their age and weight as follows: • Ages ≥ 1 month to < 6 months: 14 mg/kg/day (7 mg/kg twice daily). • Ages ≥ 6 months to < 4 years: 20 mg/kg/day (10 mg/kg 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 Apr 2008 |
Changes to the protocol included revision of inclusion and exclusion criteria, the schedule of PK assessments as well as some logistical aspects of the study procedures in order to facilitate the recruitment of subjects. The minimum required number of complete sets of PK sampling per maximum 4 days in-patient hospitalization during the Evaluation Period was lowered from 2 sets to 1 set of PK sampling. Also, the sample scheduled to be taken pre-dose was replaced by a sample collected 3-10 minutes after the start of infusion to maximize the number of samples during the Evaluation Period. |
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18 Sep 2008 |
Changes to the protocol included updates to exclusion criteria, administrative changes, clarification of study objectives (main goal of study is safety and tolerability of levetiracetam IV in pediatrics, with a lesser emphasis on PK) and addition of FDA requests that approximately 1/2 of the subjects are exposed to at least 3 consecutive levetiracetam IV doses and at least 1/3 of the subjects should be in the high dose range [i.e. Subjects ≥ 1 month to < 6 months: ≥ 28 mg/kg/day (i.e. 14 mg/kg b.i.d.); subjects ≥ 6 months to < 4 years: ≥ 40 mg/kg/day(i.e. 20 mg/kg b.i.d.)]. Results of simulations of exposure in children from 1 month to 4 years of age performed to evaluate the necessity of a dose adjustment and to establish a nomogram (study N01288) showed that children aged 1 to 6 months would require about 70% of the dose for a 4 year old. Therefore levetiracetam IV dosage was updated. |
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08 Oct 2009 |
Rationale: Changes to the protocol included revision of the inclusion of the age categories to have more balanced age groups (updated categories of 6 subjects ≥1 month to <6months; 6 subjects ≥6 months to <2 years; and 6 subjects ≥2 years to <4 years), clarification of the use of local laboratory and ECG results for the evaluation of subjects’ eligibility. Study team members’information was also updated. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/23533164 |
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