A 19-week Cognition Study of Levetiracetam in Children With Partial Onset Seizures

Study Overview
=================
Brief Summary
-----------------
A 12-week Evaluation Period will be used to characterize potential cognitive and neuropsychological effects of LEV (20 - 60 mg/kg/day), as adjunctive treatment in children 4 - 16 years old, inclusive, with refractory partial onset seizures when compared to adjunctive treatment with placebo.

Official Title
-----------------
A 19-week, Randomized, Double-blind, Multicenter, Placebo-controlled Safety Study to Evaluate the Cognitive and Neuropsychological Effects of Levetiracetam 20 - 60 mg/kg/Day, Divided in Twice Daily Dosing, as Adjunctive Treatment in Children 4 - 16 Years Old, Inclusive, With Refractory Partial Onset Seizures

Conditions
-----------------
Epilepsy, Partial

Intervention / Treatment
-----------------
* Drug: Levetiracetam
* Other: Placebo (PB)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pediatric subjects (4 - 16 years old) diagnosed with refractory partial onset seizures for a minimum of six months prior to Visit 1 experiencing at least two partial onset seizures during the four weeks prior to Visit 1 will be enrolled Subjects should be on a stable regimen of one or a maximum of two other antiepileptic drugs (AEDs) for at least 2 weeks prior to Visit 1 Subject must have an Intelligence Quotient (IQ) as assessed during Visit 1 of at least 70 Subject and parent/guardian should be fluent in English Exclusion Criteria: Subject must not have had previous treatment with levetiracetam unless, in the opinion of the investigator, the subject's previous treatment was inadequate in dose or duration to provide an accurate assessment of the therapy, or the effect of levetiracetam was confounded by concomitant medication Subject is receiving benzodiazepines on a routine or chronic basic and is unable to discontinue use four weeks prior to Visit 1 Subject has seizures too close together to accurately count Subject has a current psychiatric disorder other than mild to moderate attention deficit, behavior, or learning disorders

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam (LEV)<br>Oral tablets or oral solution at 20-60 mg/kg/d, divided into twice daily dosing. | Drug: Levetiracetam<br>* Oral tablets or oral solution at 20-60 mg/kg/d, divided into twice daily dosing.<br>* Other names: Keppra;|
| Placebo Comparator: Matching Placebo (PBO)<br>Oral tablets and oral solution. | Other: Placebo (PB)<br>* Oral tablets and oral solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Leiter International Performance Scale-Revised (Leiter-R) Attention and Memory (AM) Battery's Memory Screen Composite Score from Baseline (Visit 2) to the end of the Evaluation Period (Week 12 or Early Discontinuation Visit) | The Leiter-R includes two groupings of sub-tests: (1) the Visualization and Reasoning (VR) Battery with 10 sub-tests of nonverbal intellectual ability related to visualization, reasoning, and spatial ability; and (2) the Attention and Memory (AM) Battery with 10 sub-tests of nonverbal attention and memory function. The Examiner Rating Scale has 49 items that describe the child's activity level, attention, impulse control, and other emotional characteristics that may interact with test performance. The focus of the items is on actions, verbalizations, moods and other behaviors of the child. The examiner rates the child using the following scale: 0 = rarely or never; 1 = sometimes; 2 = often; 3 = usually or always. | Baseline (Visit 2) to the end of the Evaluation Period (Week 12 or Early Discontinuation Visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) General Memory from Baseline to Week 12 or Early Discontinuation Visit (EDV) | The WRAML-2 is comprised of 2 Verbal, 2 Visual, and 2 Attention-Concentration sub-tests, yielding a Verbal Memory Index, a Visual Memory Index and an Attention-Concentration Index. Together these sub-tests yield a General Memory Index. Scaled and standard scores allow performance comparisons based on age and 4 delayed recall sub-tests include guidelines for determining the level of recall. A composite General Memory Index score will be computed. | Baseline to Week 12 or EDV | 
| Change from Baseline in Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) Visual Memory Index from Baseline to Week 12 or Early Discontinuation Visit (EDV) | The WRAML-2 is comprised of 2 Verbal, 2 Visual, and 2 Attention-Concentration sub-tests, yielding a Verbal Memory Index, a Visual Memory Index and an Attention-Concentration Index. Together these sub-tests yield a General Memory Index. Scaled and standard scores allow performance comparisons based on age and 4 delayed recall sub-tests include guidelines for determining the level of recall. A composite General Memory Index score will be computed. | Baseline to Week 12 or EDV | 
| Change from Baseline in Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) Verbal Memory Index from Baseline to Week 12 or Early Discontinuation Visit (EDV) | The WRAML-2 is comprised of 2 Verbal, 2 Visual, and 2 Attention-Concentration sub-tests, yielding a Verbal Memory Index, a Visual Memory Index and an Attention-Concentration Index. Together these sub-tests yield a General Memory Index. Scaled and standard scores allow performance comparisons based on age and 4 delayed recall sub-tests include guidelines for determining the level of recall. A composite General Memory Index score will be computed. | Baseline to Week 12 or EDV | 
| Change from Baseline in Wide Range Assessment of Memory and Learning-Second Edition (WRAML-2) Attention/Concentration Index from Baseline to Week 12 or Early Discontinuation Visit (EDV) | The WRAML-2 is comprised of 2 Verbal, 2 Visual, and 2 Attention-Concentration sub-tests, yielding a Verbal Memory Index, a Visual Memory Index and an Attention-Concentration Index. Together these sub-tests yield a General Memory Index. Scaled and standard scores allow performance comparisons based on age and 4 delayed recall sub-tests include guidelines for determining the level of recall. A composite General Memory Index score will be computed. | Baseline to Week 12 or EDV | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Partial onset seizures, epilepsy, levetiracetam, Keppra, cognition, behavior, pediatry