A Double-blind, Placebo-controlled Study of Levetiracetam in Epilepsy Patients With Generalized Tonic-clonic Seizures (Except Partial Seizures Evolving to Secondarily Generalized Seizures)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and tolerability of levetiracetam treatment used as adjunctive therapy in Japanese and Chinese epilepsy patients aged ≥16 years and with uncontrolled Generalized Tonic-Clonic seizures despite treatment with 1 or 2 anti-epileptic drugs.

Official Title
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A Double-blind, Multicenter, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Treatment With Oral Levetiracetam, in Epilepsy Patients Aged ≥16 Years, With Generalized Tonic-clonic (GTC) Seizures

Conditions
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Epilepsy, Generalized Tonic-Clonic Seizures

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An epilepsy patient with generalized tonic-clonic seizures that are classifiable according to the ILAE 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 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 imagining features A history of convulsive or non-convulsive 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: 16 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo for 28 weeks | Drug: Placebo<br>* Matching oral placebo tablets twice daily for 28 weeks<br>|
| Experimental: Levetiracetam<br>Levetiracetam treatment with flexible dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks | Drug: Levetiracetam<br>* Oral dose at flexible increase doses: 1000 mg/day or 2000 mg/day or 3000 mg/day, twice daily, 28 weeks<br>* Other names: Keppra®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From the Combined Baseline in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 28-week Treatment Period (Dose Adjustment + Evaluation Periods) | Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from Combined Baseline B over the Treatment Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)*100. Percentage change from baseline is not defined for subjects whose baseline information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency over the 28-week treatment Period. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline | From Baseline to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Over the Evaluation Period | Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from combined baseline B over the Evaluation Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)*100. Percentage change from baseline is not defined for subjects whose baseline Information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline. | From Baseline to Evaluation Period (Week 12 to Week 28) | 
| 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 | A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Treatment Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline | From Baseline to Week 28 | 
| 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 Evaluation Period | A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Evaluation Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline | From Baseline to Evaluation Period (Week 12 to Week 28) | 
| Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period | A subject with a non-missing weekly generalized tonic-clonic (GTC) baseline seizure frequency and a weekly GTC seizure frequency of zero throughout the Evaluation Period, is considered as a GTC seizure-free subject on the Evaluation Period. | Evaluation Period (Week 12 to Week 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levetiracetam, epilepsy, generalized tonic-clonic