Trial to Demonstrate the Efficacy and Safety of Conversion to Lacosamide Monotherapy for Partial-onset Seizures

Study Overview
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Brief Summary
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The objective of this historical-controlled trial is to demonstrate the efficacy and safety of conversion to Lacosamide monotherapy in subjects with Partial-onset Seizures who are withdrawn from 1 to 2 marketed antiepileptic drugs.

Detailed Description
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Sudden unexplained death in epilepsy have been reported in epilepsy patients. A causal relationship with the administration of antiepileptic drugs has not been established. The most important known risk factor for sudden unexplained death in epilepsy (SUDEP) is the occurrence and frequency of generalized tonic-clonic seizures (GTCS). Twenty-seven patients with only GTCS were enrolled in the conversion to monotherapy study. In this study, two patients with only GTCS had SUDEP. Due to the potential increased risk of SUDEP in patients with only GTCS in a trial setting, the 1 remaining patient with only GTCS was withdrawn from this study.

Official Title
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A Historical-controlled, Multicenter, Double-blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400 mg/Day Monotherapy in Subjects With Partial-onset Seizures

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lacosamide
* Drug: Lacosamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a diagnosis of Epilepsy with Simple Partial Seizures (motor component) and or Complex Partial Seizures (with or without secondary generalization) Must be experiencing 2 to 40 seizures per 28-day period Stable dose of 1 or 2 marketed antiepileptic drugs Second Antiepileptic Drug (AED) must be less than or equal to 50 % of the minimum recommended maintenance dose per USA product label at screening Exclusion Criteria: Subject has a history of primary generalized or unclassified seizures Seizure disorder primarily characterized by isolated auras History of status epilepticus Seizures that are uncountable due to clustering Has greater than 5 seizures/day Subjects taking Benzodiazepines, Phenobarbital or Primidone Subject has Vagus Nerve Stimulation (VNS) Significant medical or psychiatric condition History of alcohol or drug abuse History of Ethosuximide use, Felbamate use after 1994 or Vigabatrin use after 1997

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lacosamide 400 mg/day<br>Lacosamide 400 mg/day | Drug: Lacosamide<br>* 50 mg and 100 mg tablets provided for 200 mg twice daily dosing for up to 20 weeks.<br>* Other names: Vimpat;|
| Active Comparator: Lacosamide 300 mg/day<br>Lacosamide 300 mg/day | Drug: Lacosamide<br>* 50 mg and 100 mg tablets provided for 150 mg twice daily dosing for up to 20 weeks.<br>* Other names: Vimpat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects (Using Kaplan-Meier) Who Are Identified As Meeting At Least 1 Pre-defined Exit Criteria By Day 112 Relative To The Start of Withdrawal of Background Antiepileptic Drug(s) | Pre-defined exit criteria: A 2-fold or greater increase in average monthly (28-day) partial seizure frequency (motor and non-motor) compared to average monthly partial seizure frequency (motor and non-motor) during the Baseline Phase A 2-fold or greater increase in consecutive 2-day partial seizure frequency (motor and non-motor) versus the highest consecutive 2-day partial seizure frequency (motor and non-motor) that occurred during the Baseline Phase. Note: if the highest consecutive 2-day partial seizure frequency during the Baseline Phase is 1, a 2-day partial seizure frequency of ≥3 is required to meet this exit criterion Occurrence of a single generalized tonic-clonic seizure if none had occurred in the 6 months prior to randomization A prolongation or worsening of overall seizure duration, frequency, type or pattern considered by the investigator as serious enough to warrant trial discontinuation Status epilepticus, or new onset of serial/cluster seizures | 16 Weeks Maintenance Period (approximately 112 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Any Exit Event During The Maintenance Period | The time to first occurrence (days) of any exit event was estimated using Kaplan-Meier methods and was based on the time from the start of the Maintenance Phase to the earliest date a subject met an exit criterion. Subjects who discontinued during the Maintenance Phase due to non-exit criteria reasons or who completed the Maintenance Phase before 112 days and did not meet an exit criterion were censored as of the last Maintenance Phase dose date. Subjects completing 112 days in the Maintenance Phase were censored as of Day 112. | 16 Weeks Maintenance Period (approximately 112 days) | 
| Percentage of Subjects (Using Kaplan-Meier) Who Are Identified as Meeting at Least 1 Pre-defined Exit Criteria by Day 112, Withdrew Due to Adverse Event (AE) or Withdrew Due to Lack of Efficacy During The Maintenance Period | Subjects were classified as having an exit event if they experienced at least 1 of the following events during the Maintenance Phase as of Day 112: Met at least 1 exit criterion based on the calculations applied for the Primary Efficacy Analysis Withdrawal due to AE with onset during the Maintenance Phase Withdrew prematurely due to lack of efficacy during the Maintenance Phase The date the subject experienced the event was set to the earliest date the subject met an exit criterion or the date of the last Maintenance Phase dose for subjects not meeting an exit criterion but withdrawing due to an AE or lack of efficacy. The secondary analysis is only conducted on the Lacosamide 400 mg/day group. | 16 Weeks Maintenance Period (approximately 112 days) | 
| Duration of Monotherapy Treatment During the Monotherapy Phase of The Maintenance Period (Visit 9 - Visit 12) | Days on Monotherapy Treatment were defined as the number of days during the Monotherapy Phase when the subject took Lacosamide (LCM) only (ie, the total number of days exposed to LCM during the Monotherapy Phase minus any days where a concomitant or rescue Anti-epileptic Drug (AED) was taken by the subject). The days on Monotherapy Treatment did not need to be consecutive. | Visit 9 - Visit 12 (approximately 10 weeks) | 
| Clinical Global Impression of Change (CGIC) From Baseline To Last Visit | For the assessment of the Clinical Global Impression of Change (CGIC), the investigator should provide his/her assessment of the subject's clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status. He was asked the following:Please check the number that best describes the subject's condition over the past 4 weeks compared to Baseline: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse | Baseline; Last Visit (approximately 27 weeks) | 
| Patient's Global Impression of Change (PGIC) From Baseline To Last Visit | For the assessment of the Patient's Global Impression of Change, the subject should provide his/her assessment of his/her own clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status.The subject was asked to answer the following: Over the past 4 weeks, how have you felt compared to before you entered this clinical trial? (Please check the number that best describes your condition.) Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse | Baseline; Last Visit (approximately 27 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Partial Onset Seizures, Lacosamide, Monotherapy, Vimpat