Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures

Study Overview
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Brief Summary
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To allow pediatric patients with partial onset seizures an opportunity to receive (as follow-up to studies N01009(NCT00105040)/N01103(NCT00175890) or by direct enrollment) open-label levetiracetam treatment, continue studying cognition and behavior in children, and continue collection of safety/efficacy data.

Official Title
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A Multi-Center, Open-Label, Long-Term, Follow-Up Study Of the Safety And Efficacy Of Levetiracetam In Children With Partial Onset Seizures.

Conditions
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Epilepsy, Partial

Intervention / Treatment
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* Drug: levetiracetam (LEV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients with partial onset seizures, with 1 to 2 anti-epileptic drugs (AEDS), with participation in previous levetiracetam pediatric studies (N01009 or N01103) or direct enrollment, for whom levetiracetam treatment will be of possible benefit Exclusion Criteria: Patients on a ketogenic diet Seizures too close together to accurately count Pseudoseizures Status epilepticus 1 month prior Visit 1 Current diagnosis of Lennox-Gastaut Syndrome or epilepsy secondary to a progressing cerebral disease will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 1 Month
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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam<br> | Drug: levetiracetam (LEV)<br>* Per protocol oral tablets or oral solution at 10 to 30mg/kg/day bid for 48 weeks, or approximately 52 weeks should a subject choose to discontinue levetiracetam (LEV) at the end of the maintenance period.<br>* Other names: Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change (Reduction) of Partial (Type I) Seizure Frequency Per Week From Baseline Over Time During Treatment Period. | Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week. | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change (Reduction) of Total (Type I, II, III) Seizure Frequency Per Week From Baseline Over Time During Treatment Period. | Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week. | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 
| Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period. |  | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 
| Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period. |  | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 
| Change (Reduction) From Baseline in Partial (Type I) Seizure Frequency Per Week Over Time During Treatment Period | Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week. | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 
| Change (Reduction) From Baseline in Total (Type I, II, III) Seizure Frequency Per Week Over Time During Treatment Period | Positive changes from Baseline indicate an improvement (i.e., a reduction) in seizure frequency per week. | Up-titration/Conversion Period (2-8 weeks); Maintenance Period (2-8 weeks to 40-46 weeks) | 
| Partial Seizure (Type I) Responder Rate (Percent) During the Up-titration/Conversion Phase and by Visit During the Maintenance Phase | The responder rate is defined as the number of responders. A responder is a patient with a 50% or greater change (reduction) in partial seizure frequency per week. Note: Rates were reported as percentages. | Up-titration (4 weeks); Maintenance Visits 3-4 (weeks 4-14, 6-15, or 8-16); Visits 4-5 (weeks 14-24, 15-24, or 16-24); Visits 5-6 (weeks 24-36); Visits 6-7 (weeks 36-48) | 
| Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) | For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase. | Subjects with up to 24 weeks of exposure | 
| Partial Seizure (Type I) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) | For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase. | Subjects with greater than 24 weeks of exposure | 
| Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) | For subjects with up to 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase. | Subjects with up to 24 weeks of exposure | 
| Total Seizure (Type I, II, III) Maximum Seizure Free Interval (Percentage of Days Belonging to a Seizure Free Interval of 28 Days or More) | For subjects with greater than 24 weeks in the evaluation phase the denominator for each subject is their number of days in the evaluation phase. | Subjects with greater than 24 weeks of exposure | 
| Total Seizure (Type I, II, III) Continuously Seizure Free During the Maintenance Period | The measure description is the product limit adjusted percent of subjects seizure free starting from the beginning of the Maintenance Period. The up-titration period is the up to 6 week period of increasing dose prior to the Maintenance Period. The Maintenance Period is the period of stable dosing, subsquent to the up-titration period, which could last from 42 to 48 weeks. | greater than or equal to 24 weeks, greater than or equal to 40 weeks | 
| Percent of Subjects With Each Seizure Type During the Evaluation Period | Type I Seizure is a partial onset Seizure (see International League Against Epilepsy definitions). Type II Seizure is a Generalized Seizure (see International League Against Epilepsy definitions). Type III Seizure is a Unknown Seizure Type (see International League Against Epilepsy definitions). A subject could experience more than one seizure type. | Evaluation period (48 weeks) | 
| Investigator Global Evaluation Scale | There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change). | End of Evaluation period (week 48 or at point of early discontinuation) | 
| Parent/Guardian Global Evaluation Scale | There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change). | End of Evaluation period (week 48 or at point of early discontinuation) | 
| Subject (>=8 Years Old) Global Evaluation Scale | There are 7 categories, 3 for improvement (Marked improvement, Moderate improvement, Slight improvement), 3 for worsening (Slight worsening, Moderate worsening, Marked worsening), and 1 for no change (No change). | End of Evaluation period (week 48 or at point of early discontinuation) | 
| Leiter-R Associated Memory (AM) Memory Screen Composite Score Change From Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) (4 to 16 Year Olds) | The Leiter-R AM battery has 10 subtests. The raw scores of the subtests are converted into scaled scores. Six composite scores are constructed from the 10 subtest scaled scores. The Memory Screen is one of them. It is composed of 2 subtests the Associated Pairs and Forward Memory. The sum of the Associated Pairs and Forward Memory subtest scaled scores are converted into a Memory composite score normally distributed with a mean and standard deviation of 100 (±15). Higher scores and positive changes from baseline are better. The range of the Memory Screen composite score is 44 to 155. | Baseline to Visit 5 (Week 24) and Visit 7 (Week 48) | 
| Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Olds) | This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline. | Visit 5 (Week 24) | 
| Bayley Scale of Infant Development (BSID) II Mental Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Olds) | This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline. | Visit 7 (week 48) | 
| Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 5 (Week 24) (1 Month to < 4 Year Old) | This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline. | Visit 5 (week 24) | 
| Bayley Scale of Infant Development (BSID) II Psychomotor Development Index Scores Classification Shift From Baseline at Visit 7 (Week 48) (1 Month to < 4 Year Old) | This score is obtained from a total raw score which is the sum of a battery of individual questions. It is adjusted for a child's age, has an expected mean of 100 and standard deviation of 15, and can be categorized as: (1) Accelerated Performance (>= 115), (2) Within Normal Limits (85-114), (3) Mildly Delayed Performance (70-84), and (4) Significantly Delayed Performance (<=69). Changes from baseline are then further categorized where 'Improved' is any positive category change, 'Stable' is no category change, and 'Worsened' is any negative category change, from baseline. | Visit 7 (week 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Partial Onset Seizures, levetiracetam, Epilepsy, Keppra