A Study of Levetiracetam in Japanese Pediatric Patients With Generalized Tonic-clonic Seizures

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of Levetiracetam dry syrup at doses up to 60 mg/kg/day or 3000 mg/day used as adjunctive therapy in Japanese pediatric patients aged ≥4 to <16 years with uncontrolled Generalized Tonic-Clonic (GTC) seizures despite treatment with 1 or 2 Anti-Epileptic Drugs (AEDs).

Official Title
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An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Treatment With Levetiracetam in Japanese Patients (≥4 to <16 Years) With Uncontrolled Generalized Tonic-clonic (GTC) Seizures Despite Treatment With 1 or 2 Antiepileptic Drug(s)

Conditions
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Epilepsy, Generalized Tonic-clonic Seizures

Intervention / Treatment
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* Drug: Levetiracetam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An epileptic patient with generalized tonic-clonic seizures that are classifiable according to the International League Against Epilepsy classification of epileptic seizures (Epilepsia, 1981) A patient on a stable dose of 1 or 2 anti-epileptic drugs for the last 4 weeks (potassium bromide and sodium bromide for the last 12 weeks) prior to the Combined Baseline Period and during the Combined Baseline Period Exclusion Criteria: Presence of any sign (clinical or imaging procedures) suggesting a progressive brain lesion/disease, in particular, progressive disorder with epileptic seizures Diagnosis of Lennox-Gastaut Syndrome Confirmed focal epilepsy based on clinical signs (seizure types), with consistent electroencephalogram and magnetic resonance imaging features A history of convulsive or nonconvulsive status epilepticus while taking concomitant anti-epileptic drugs for the last 3 months prior to Visit 1

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 15 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>Twice daily (morning and evening) orally | Drug: Levetiracetam<br>* The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.<br>* Other names: E Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percent Change From the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 24-week Treatment Period (Up-Titration and Evaluation Periods) | The percent change from Combined Baseline over Treatment Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Treatment Period (T) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - T)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7 | From Baseline (Week -8) to Treatment Period (Week 0 to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percent Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Period Over the Evaluation Period | The percent change from Combined Baseline over Evaluation Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Evaluation Period (E) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below. The percent change from Baseline = (B - E)/B x 100 The seizure frequency per week was calculated using the following formula: Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7 | From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24) | 
| Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period | The 50 % responder rate during the Treatment Period was the proportion of subjects who reported a ≥ 50 % reduction in seizure frequency per week from Baseline during the Treatment Period. | From Baseline (Week -8) to Treatment Period (Week 0 to Week 24) | 
| Generalized Tonic-clonic Seizures 50 % Responder Rate During the Evaluation Period | The 50 % responder rate during the Evaluation Period was the proportion of subjects who reported a ≥50 % reduction in seizure frequency per week from Baseline during the Evaluation Period. | From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24) | 
| Generalized Tonic-clonic Seizure Freedom Over the Treatment Period | A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Treatment Period was considered a seizure-free subject for that period. | Treatment Period (Week 0 to Week 24) | 
| Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period | A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Evaluation Period was considered a seizure-free subject for that period. | Evaluation Period (Week 4 to Week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levetiracetam, Epilepsy, Generalized tonic-clonic seizures