Open-label Study of Levetiracetam Intravenous Infusion in Children (1 Month-4 Years Old) With Epilepsy

Study Overview
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Brief Summary
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Keppra injection is approved in the US as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. The objective of the current study is to assess the safety, tolerability, and pharmacokinetics, of this formulation in children aged 1 month to 4 years.

Detailed Description
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The primary objective of this study was to evaluate the safety and tolerability of levetiracetam intravenous 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 levetiracetam oral dose administration or as a new antiepileptic treatment. The evaluation period was to be considered as one complete set of 4 pharmacokinetic (PK) samples for a maximum of 4 days; For children already taking levetiracetam oral solution prior to entering the study, the levetiracetam intravenous (LEV IV) dose will be equivalent (mg-for-mg) to their oral dose (always in twice daily regimen) within the following dose range, calculated on the basis of their age and weight: Children ≥ 1 month to < 6 months: 14 mg/kg/day (i.e. 7 mg/kg twice daily) to 42 mg/kg/day (i.e 21 mg/kg/day twice daily); Children ≥ 6 months to < 4 years:20 mg/kg/day (i.e. 10 mg/kg twice daily) to 60 mg/kg/day (i.e 30 mg/kg/day twice daily). The first intravenous (IV) infusion was to be administered 12 hours after the last oral dose of levetiracetam. For children not taking levetiracetam oral solution prior to entering the study, the intravenous (IV) dose will correspond to their age and weight as follows: Children ≥ 1 month to < 6 months: 14 mg/kg/day (i.e. 7 mg/kg twice daily). Children ≥ 6 months to < 4 years: 20 mg/kg/day (i.e. 10 mg/kg twice daily). However, when necessary for the safety of the subject or when the investigator deemed it appropriate the levetiracetam intravenous (LEV IV) dose could be modified after one day. Subjects were hospitalized for the duration of the levetiracetam intravenous (LEV IV) treatment.

Official Title
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Open-label, Single-arm, Multi-center, Pharmacokinetic, Safety and Tolerability Study of Levetiracetam Intravenous Infusion in Children (1 Month- 4 Years Old) With Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Levetiracetam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 1 month and 4 years of age, inclusive The subject suffers from epilepsy (except status epilepticus) The subject is requiring levetiracetam IV treatment in place of oral therapy for a short period of time Exclusion Criteria: The subject has difficult venous accessibility History of status epilepticus during the 3 months prior to Screening The subject is on felbamate with less than 18 months continuous exposure before Screening. The subject presents with current depressive symptoms, current suicidal ideation and/or behavior.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam<br> | Drug: Levetiracetam<br>* 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).<br>* Other names: ucb L059;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days) |  | Treatment period (up to 4 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Received High-dose Levetiracetam Intravenous (LEV IV) (More Than 28 mg/kg/Day for Subjects <6 Months; >40mg/kg/Day for Subjects ≥6 Months) During the Treatment Period (up to 4 Days) |  | Treatment period (up to 4 days) | 
| Number of Consecutive Levetiracetam Intravenous (LEV IV) Doses Received |  | Treatment period (up to 4 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Child, Levetiracetam, Keppra®, Infusion, Intravenous