eValuation of the Efficacy and toleRability of Vimpat When Added to lEvetiracetam

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effectiveness of the study drug lacosamide (200-600 mg/day) when added to a stable dose of levetiracetam (1000-3000 mg/day) with withdrawal of the concomitant sodium channel blocking-antiepileptic drug (AEDs) in subjects not well controlled on their current regimen.

Official Title
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Open-label, Single Arm, Study Evaluating Tolerability and Efficacy of Lacosamide When Added to Levetiracetam With Withdrawal of Concomitant Sodium Channel Blocking Antiepileptic Drug in Subjects With Uncontrolled Partial-onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lacosamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female, at least 18 years of age Subject has a diagnosis of epilepsy with partial-onset seizures according to the International Classification of Epileptic Seizures (1981) Subject is taking levetiracetam (LEV) in combination with 1 sodium channel blocking antiepileptic drug (defined as carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or eslicarbazepine) as adjunctive treatment for epilepsy The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average ≥ 2 partial-onset seizures per 28 days with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline. Additionally, subjects must experience at least 1 seizure during the 4-week Prospective Seizure Baseline Subject has been maintained on a stable dose of LEV and a sodium channel blocking antiepileptic drug (SCB-AED) for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average ≥ 2 partial-onset seizures per 28 days (based on investigator assessment of subject report) with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline Subject has been maintained on a stable dose of levetiracetam (LEV) and a sodium channel blocking antiepileptic drug (SCB-AED) for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline, with or without additional concurrent stable vagal nerve stimulation (VNS). The VNS must have been in place for at least 6 months prior to the Screening Visit (Visit 1) with constant settings for at least 4-weeks prior to the Screening Visit (Visit 1) and throughout the duration of the study Exclusion Criteria: Previous use of lacosamide History of alcohol or drug abuse History of seizure disorder characterized primarily by isolated auras History of primary generalized seizures History of status epilepticus within the 12-months History of clustering seizures Nonepileptic events, including pseudoseizures that could be confused with seizures History of any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this study Lifetime history of suicide attempt, or suicidal ideation in the past 6 months Hypersensitivity to any component of lacosamide (LCM) History of acute or sub-acute progressive central nervous system disease History of severe anaphylactic reaction or serious blood dyscrasias Impaired renal function (ie, Creatinine Clearance (CLcr) is lower than 30 mL/min) at Visit 1 History of sick sinus syndrome without a pacemaker, or atrioventricular (AV) block, or subject has any other clinically significant electrocardiogram (ECG) abnormalities History sodium channelopathy, such as Brugada syndrome History of myocardial infarction in the last 3 months

Ages Eligible for Study
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Minimum Age: 18 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: Lacosamide<br>Lacosamide will be added to levetiracetam while withdrawing the sodium channel blocking antiepileptic drug (AED) | Drug: Lacosamide<br>* 50 mg and 100 mg lacosamide tablets will be combined and taken in two equal doses per day to provide the required total daily dosage of 100 - 600 mg/day. Subjects were titrated to a minimum of 200 mg/ day during the Treatment Period. Maximum duration of study drug administration is approximately 23 weeks.<br>* Other names: Harkoseride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention at the End of the 21-week Treatment Period | Retention is a summary measure that integrates both the patient's and clinician's assessment of efficacy and tolerability in epilepsy clinical studies to provide a measure of effectiveness. | Duration of the Treatment Period (21 Weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lacosamide, Epilepsy, Levetiracetam, Sodium Channel Blockers