Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures
Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures
The purpose of this trial is to assess the efficacy, safety and tolerabilty of lacosamide
 administered as add-on therapy with 1 to 3 anti-seizure medications. This trial is for
 children aged 1 month to less than 4 years with epilepsy who currently have uncontrolled
 partial-onset seizures.
The trial consists of a 7-day Baseline Period, a 20-day Titration Period, a 7-day Maintenance
 Period, and a 12-day Transition Period for subjects who complete the study and choose to
 enter the extension study. Subjects who will not enter the extension study will continue
 after the Maintenance Period with a 16-day Taper Period followed by a 30-day Safety Follow-Up
 Period. The Taper Period and Safety Follow-Up are also applicable for subjects not eligible
 for continuation and therefore ending the study earlier.

 If subjects meet the eligibility criteria, they will be randomized to receive either
 lacosamide 8 mg/kg/day to 12 mg/kg/day, or placebo during the Maintenance Phase. The dose of
 lacosamide will be titrated from 4 mg/kg/day at study start to maximum of 12 mg/kg/day at
 4-day intervals of 1-2 mg/kg/day.

 All subjects who complete the 20-day Titration Period will enter the 7-day Maintenance
 Period. No dose adjustment is allowed during the Maintenance Phase. The Treatment Phase is
 defined as the combined Titration and Maintenance Phases.
Inclusion Criteria:

 -  Subject is male or female from >=1 month (ie, 4 weeks after full term [37 weeks
 gestational age]) to <4 years of age

 -  Subject has a diagnosis of epilepsy with partial-onset seizures. The results of >=1
 prior EEG and >=1 magnetic resonance imaging/computerized tomography scan should be
 consistent with this diagnosis

 -  Subject weighs >=4 kg to <30 kg at Visit 1

 -  Subject has experienced >=2 partial-onset seizures with or without secondary
 generalization during each consecutive 7-day period during the 2 weeks prior to Visit
 1

 -  Subject has >=2 partial-onset seizures with or without secondary generalization during
 the End-of-Baseline video-EEG. Electrographic seizures are defined as recognizable
 ictal patterns on an EEG involving >=2 contiguous electrodes. The seizures are
 initiated as a unilateral or strongly asymmetric abnormal epileptiform discharge
 lasting a total of >10 seconds

 -  Subject is on a stable (concurrently or sequentially) dosage regimen of 1 to 3 AEDs.
 The dosage regimen of concomitant AED therapy must be kept constant for a period of
 >=2 weeks prior to Visit 1. A stable daily dosage regimen of a concomitant
 benzodiazepine (BZD) will be considered as a concomitant AED

 -  Vagus nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED.
 The VNS device must have been implanted for >=6 months prior to Visit 1; device
 settings must be kept stable for >=2 weeks prior to Visit 1 and kept stable during the
 Baseline, Treatment, and Transition Periods. Use of the VNS device magnet is allowed

 -  Subject is an acceptable candidate for venipuncture

 Exclusion Criteria:

 -  Subject has experienced febrile seizures exclusively. The occurrence of febrile
 seizures in addition to partial-onset seizures is not exclusionary

 -  Subject is on a ketogenic diet that has either changed within the 4 weeks prior to
 Visit 1 or is expected to change during the study

 -  Subject has creatinine clearance <30 mL/minute

 -  Subject has a clinically relevant ECG abnormality, in the opinion of the investigator
 (eg, second or third degree heart block at rest or a corrected QT interval [QTc] >=450
 ms)

 -  Subject has a hemodynamically significant congenital heart disease

 -  Subject has an arrhythmic heart condition requiring medical therapy

 -  Subject has a known history of severe anaphylactic reaction secondary to medication
 intake or serious blood dyscrasias

 -  Subject has nonepileptic events that could be confused with seizures. Subjects may be
 included if epileptic events can be clearly distinguished and the frequency meets the
 study inclusion criteria

 -  Subject has a current diagnosis of Lennox-Gastaut syndrome, epilepsia partialis
 continua, primary generalized epilepsy, Dravet Syndorme, or seizures that are not of
 partial-onset origin

 -  Subject has a history of generalized convulsive status epilepticus <=2 months prior to
 Screening (Visit 1)

 -  Subject has been treated with felbamate and has experienced any serious toxicity
 issues (defined as liver failure, aplastic anemia) with this treatment. Subjects
 treated with felbamate for <12 months are excluded. Subjects treated with felbamate
 for >=12 months prior to Visit 1 and who have not experienced serious toxicity issues
 are eligible

 -  Subject has an acute or subacutely progressive central nervous system disease. Subject
 has epilepsy secondary to a progressing cerebral disease or any other progressively
 neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome)

 -  Subject has a known cardiac sodium channelopathy, such as Brugada syndrome