An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures

Study Overview
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Brief Summary
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Objective of the First Period: To evaluate the efficacy of Levetiracetam dry syrup at doses up to a maximum of 60 mg/kg/day or 3000 mg/day used as an adjunctive therapy in Japanese pediatric patients (4 to 16 years) with uncontrolled partial seizures despite treatment with 1 or 2 anti-epileptic drug(s).

Detailed Description
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Objectives of the Second Period: To provide the Levetiracetam treatment to subjects who are judged by the investigators to benefit from the long-term treatment and who are willing to continuously receive this drug. To continuously evaluate the safety of the Levetiracetam long-term administration at doses ranging from 20 mg/kg/day or 1000 mg/day to 60 mg/kg/day or 3000 mg/day in subjects who completed the First Period of this study.

Official Title
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An Open Label, Single-Arm, Multi-Center Study on the Efficacy, Safety and Pharmacokinetics of Levetiracetam in Pediatric Patients (4 to 16 Years) With Partial Seizures Despite Treatment With 1 or 2 Anti-Epileptic Drugs

Conditions
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Epilepsy, Partial Seizures

Intervention / Treatment
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* Drug: Levetiracetam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has partial Epilepsy and the diagnosis must be confirmed in the last 6 months The patients must be on a stable 1 or 2 anti-epileptic drug(s) treatment during the 4 weeks prior to Baseline and must have at least 8 partial seizures during the 8-week prospective Baseline Period Patient at the age of 4 to 16 years, and at the body weight of 11 to 82 kg Exclusion Criteria: The patient has a treatable seizure etiology The patient has Epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases The patient has a history of status Epilepticus during the 3 months prior to Visit 1 The patient has a past and present history of pseudo seizures The patient has a 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam<br>Open-label, single-arm | Drug: Levetiracetam<br>* First Period: Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks. Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.<br>* Other names: Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period | The change in partial seizure frequency from Baseline (B) over the Treatment Period (T) is given as a percentage reduction computed as: (B values- T values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline during the first 14-week Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)); Week 0-22 | 
| Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Second Period (up to Three Years Until the Time of Approval Granted) | An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with the pharmaceutical product. Incidence of treatment-emergent AEs is reported by the percentage of subjects with at least one treatment-emergent AE. | During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Partial Seizure Frequency Per Week Over the 10-week Evaluation Period | The change in partial seizure frequency from Baseline (B) over the Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline to the 10-week Evaluation Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | From Baseline (Week 0-8) to the 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) | 
| Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period | The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Treatment Period/number of days for observation in the Treatment Period) x 7. Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) | 
| Partial Seizure Frequency Per Week Over the 10-weeks Evaluation Period | The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Evaluation Period/number of days for observation in the Evaluation Period) x 7. Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) | 
| Percentage of Partial Seizures 50 % Responders Over the 14-weeks Treatment Period | 50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Treatment Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) | 
| Percentage of Partial Seizures 50 % Responders Over the 10-weeks Evaluation Period | 50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Evaluation Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) | 
| Number of Seizure-free Subjects Over the 14-weeks Treatment Period | Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) | 
| Number of Seizure-free Subjects Over the 10-weeks Evaluation Period | Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: Simple partial seizures Complex partial seizures Partial seizures evolving to secondarily generalized seizures. | 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) | 
| Incidence of Treatment-emergent Adverse Drug Reactions (ADRs) During the Second Period (up to Three Years Until the Time of Approval Granted) | An Adverse Drug Reaction (ADR) is an Adverse Event for which a causal relationship between the product and the occurrence is suspected. Incidence of ADRs is reported by the number of subjects with at least one ADR. | During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted) | 
| Change From Baseline in Partial Seizure Frequency Per Week for the Second Period (up to Three Years From Informed Consent Until the Time of Approval Granted) | The outcome was also calculated for each 3-month Period but here only the result for the total Second Evaluation Period (Second Period without following 6-weeks Withdrawal Period for withdrawers) is presented. Change in partial seizure frequency from Baseline (B) over Second Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction show a decrease from Baseline. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. | From Baseline (Week 0-8) until the time of approval granted (up to three years from date of informed consent (Week 0); without 6-weeks Withdrawal Period) | 

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