Open-Label Study to Assess Lacosamide Safety as Add-on Therapy for Primary Generalized Tonic-Clonic Seizures in Subjects With Epilepsy

Study Overview
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Brief Summary
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The purpose is to assess the safety of Lacosamide in subjects with uncontrolled Primary Generalized Tonic-Clonic (PGTC) seizures with Idiopathic Generalized Epilepsy.

Official Title
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An Open-Label Pilot Study to Assess the Safety of Oral Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy

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 has a diagnosis of uncontrolled epilepsy with primary generalized tonic-clonic (PGTC) seizures and idiopathic generalized epilepsy. Diagnosis should have been established by an electroencephalogram (EEG) with generalized spike-wave discharges within 5 years of the screening visit Subject has ≥1 PGTC seizure within the 12 weeks prior to the screening visit Subject has a stable dose regimen of 1 to 3 marketed antiepileptic drug(s) (AEDs) with or without additional concurrent stable Vagus Nerve Stimulation (VNS). The VNS must have been in place for at least 6 months prior to study entry with constant settings for at least 28 days prior to the screening visit and during the Baseline Phase. Benzodiazepines will be counted as an AED Exclusion Criteria: Subject has a history of partial-onset seizures or EEG findings consistent with partial onset seizures Subject has a history of status epilepticus within the 5-year Period prior to Visit 1 Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events Subject has any medical or psychiatric condition Subject has any history of alcohol or drug abuse Subject is currently taking felbamate Subject has ever taken vigabatrin and has no visual fields examination report available or if results of the examination are abnormal Subject is on a ketogenic diet Subject has a known sodium channelopathy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 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> | Drug: Lacosamide<br>* Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.<br>* Other names: Vimpat®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase | During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: Seizure type Seizure frequency A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures. | From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) | 
| Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase | During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: Seizure type Seizure frequency A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures. | From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours. | From Visit 2 (Week 4) to Visit 6 (Week 8) | 
| Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours. | From Visit 2 (Week 4) to Visit 6 (Week 8) | 
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. | From Visit 2 (Week 4) to Visit 7 (Week 13) | 
| Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. | From Visit 2 (Week 4) to Visit 7 (Week 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Generalized Tonic-Clonic (PGTC) Seizures, Absence Seizures, Myoclonic Seizures, Idiopathic Generalized Epilepsy (IGE)