Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures

Study Overview
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Brief Summary
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Double-blind, randomized, placebo-controlled, multi-center clinical trial conducted to evaluate levetiracetam as adjunctive therapy in children (4-16 years) with refractory partial onset seizures.

Official Title
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Evaluation of the Efficacy and Tolerability of Levetiracetam Add-On Treatment in Refractory Pediatric Patients With Partial Onset Seizures: A 28-Week Double-Blind, Placebo-Controlled Multi-center Trial

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of epilepsy with uncontrolled partial onset seizures, whether or not secondarily generalized, and the diagnosis was >= 6 months before the Selection Visit epilepsy was classifiable according to the ILAE Classification >= 4 partial onset seizures during the 4 weeks preceding the Selection Visit and were required to have >= 4 partial onset seizures during each 4-week interval of the Baseline Period to qualify for randomization unsatisfactory current AED treatment in terms of efficacy and/or safety stable AED treatment consisting of no more than two AEDs Exclusion Criteria: treatable seizure etiology epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases history of status epilepticus which required hospitalization during 3 months prior to the Selection Visit history of or the presence of pseudo seizures current diagnosis of Lennox-Gastaut syndrome

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam (LEV)<br>LEV dose was titrated to a level of 60 mg/kg/day. The initial dose level was 20 mg/kg/day for the first two weeks, followed by a dose level of 40 mg/kg/day for two weeks. If lower doses were well tolerated, the LEV dose was increased to a dose level of 60 mg/kg/day for the remaining 10 weeks. The dose level could be reduced to 40 mg/kg/day if the patient did not tolerate LEV at a dose level of 60 mg/kg/day. | Drug: Levetiracetam<br>* high total tablet weight (HTTW) formulation in tablet strengths of 166.5 mg, 250 mg, and 500 mg was used for patients weighing at least 40.1 kg low total tablet weight (LTTW) formulation in tablet strengths of 166 mg and 250 mg was used for patients weighing 40 kg or less<br>|
| Placebo Comparator: Placebo<br>Subjects received Placebo matching to LEV treatment. | Drug: Placebo<br>* Placebo tablets for oral administration that were identical in appearance to the respective formulations (LTTW and HTTW) were used as reference therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial onset seizure frequency (Type I, Type IC included) per week during the Treatment period | Calculated as 7-day partial onset seizure frequency. | During the 14-weeks Treatment period (Week 8 to Week 22) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% responder rate in seizure frequency per week during the Treatment Period | Response rate is defined as percent of patients experiencing at least a 50% reduction from baseline in the seizure frequency per week during the Treatment Period. | During the 14-weeks Treatment period (Week 8 to Week 22) | 
| Percent of patients with categorized reduction from baseline in seizure frequency per week during the Treatment Period | Categories as follows: <-25%, -25% to <25%, 25% to <50%, 50% to <75%, 75% to <100%, and 100% | From Baseline to the 14-weeks Treatment period | 
| Change from baseline in the average duration of seizure free intervals | Intervals are defined as seizure-free if no seizures are reported. | From Baseline to the 14-weeks Treatment period | 
| Number of seizure free days during the Treatment Period | A day is regarded as seizure-free if no seizures are reported. | During the 14-weeks Treatment period (Week 8 to Week 22) | 
| Absolute change from baseline in partial onset seizure frequency per week during the Treatment Period | Absolute change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 14-weeks Treatment period (Week 8 to Week 22) | 
| Absolute change from baseline in partial onset seizure frequency per week during the Titration Period | Absolute change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 6-weeks Titration period (Week 8 to Week 14) | 
| Absolute change from baseline in partial onset seizure frequency per week during the Evaluation Period | Absolute change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22) | 
| Percent change from baseline in partial onset seizure frequency per week during the Treatment Period | Percent change from baseline in partial onset seizure frequency during the Treatment Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 14-weeks Treatment period (Week 8 to Week 22) | 
| Percent change from baseline in partial onset seizure frequency per week during the Titration Period | Percent change from baseline in partial onset seizure frequency during the Titration Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 6-weeks Titration period (Week 8 to Week 14) | 
| Percent change from baseline in partial onset seizure frequency per week during the Evaluation Period | Percent change from baseline in partial onset seizure frequency during the Evaluation Period standardized to 1 week period. A negative value in absolute change from baseline indicates a decrease in partial onset seizure frequency from baseline. | Baseline, During the 8-weeks Evaluation period (Week 14 to Week 22) | 
| Cumulative percentage of patients who were seizure-free since the beginning of the Evaluation Period | A subject was regarded as seizure-free if not seizures were reported since the beginning of the Evaluation Period. | Beginning of the Evaluation Period (Week 14) | 
| Partial onset seizure frequency per week during the Titration Period | Calculated as 7-day partial onset seizure frequency. | During the 6-weeks Titration period (Week 8 to Week 14) | 
| Partial onset seizure frequency per week during the Evaluation Period | Calculated as 7-day partial onset seizure frequency. | During the 6-weeks Evaluation period (Week 8 to Week 14) | 
| Total seizure frequency per week (Types I + II + III) during the Treatment Period | Calculated as 7-day partial onset seizure frequency. | During the 14-weeks Treatment period (Week 8 to Week 22) | 
| Total seizure frequency per week (Types I + II + III) during the Titration Period | Calculated as 7-day partial onset seizure frequency. | During the 6-weeks Titration period (Week 8 to Week 14) | 
| Total seizure frequency per week (Types I + II + III) during the Evaluation Period | Calculated as 7-day partial onset seizure frequency. | During the 6-weeks Evaluation period (Week 8 to Week 14) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levetiracetam, Keppra