Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures

Study Overview
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Brief Summary
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To assess the long-term effects of levetiracetam on retention rate in subjects with refractory partial onset seizure that are not fully controlled with 1 to 3 concomitant antiepileptic drugs, compared to topiramate as add-on therapy during 52 weeks.

Official Title
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A Randomized, Open-label, Parallel Group, Multi-center, Comparative, Phase IV Trial of Levetiracetam (LEV) Versus Topiramate (TPM) as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Topiramate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects from 16 to 80 years, inclusive. Subjects under 20 years may only be included where legally permitted and ethically accepted Subjects with refractory epilepsy with partial onset seizure classifiable according to the International League Against Epilepsy (ILAE). Subjects having at least 2 partial onset seizures whether or not secondarily generalized during the 8 weeks historical baseline preceding V1 according to ILAE classification Subjects having at least 1 partial onset seizures whether or not secondarily generalized per 4 weeks preceding V2 according to ILAE classification Subjects with each interval of partial onset seizures less than 6 weeks during entire 12 weeks (8 weeks preceding V1 and 4 weeks preceding V2) Subjects being uncontrolled while treated by 1 to 3 permitted concomitant AEDs. Permitted concomitant AEDs having been stable and at optimal dosage for the subject from at least 4 week before V1 and during 4 weeks preceding V2 and expected to be kept stable during the Treatment Period. Exclusion Criteria: Subjects presenting any generalized epilepsies classified as type II according to the ILAE classification (ref to publication from 1981) Subjects suffering from epilepsies and syndromes undetermined whether focal or generalized (classification III according to the ILAE classification) Subjects suffering from special syndromes (classification IV according to the ILAE classification) History or occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before V2. Presence of exclusively type IA non-motor seizures. History or presence of status epilepticus within last 3 months preceding V1 or during Baseline History or presence of known pseudo-seizures Subjects who are currently on vigabatrin. (Subjects who received vigabatrin in the past and have a normal visual field test are allowed.) Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: antipsychotics drugs, and psychostimulant (amphetamine derivatives)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levetiracetam<br>250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks | Drug: Levetiracetam<br>* 250 mg and 500 mg levetiracetam tablet 1000 mg/day (500 mg bid) levetiracetam (maximum to 3000 mg/day) Duration: maximum 52 weeks<br>* Other names: Keppra;|
| Active Comparator: Topiramate<br>25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks | Drug: Topiramate<br>* 25 mg and 100 mg topiramate tablet 100 mg/day(50 mg bid) topiramate (maximum to 400 mg/day) Duration: maximum 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate |  | From Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52 |  | From Baseline to Week 52 | 
| Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE) |  | From Baseline to Week 52 | 
| Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 | Reduction from baseline was defined as baseline value minus post-baseline value and therefore is the negative of the change from baseline value. | From Baseline to Week 52 | 
| Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52 |  | From Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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levetiracetam, topiramate, epilepsy, partial seizures