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

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

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.

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.

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.

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

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