Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures
Condition: Epilepsy With Partial-onset Seizures
MeSH terms: Epilepsy; Seizures
Intervention: Lacosamide; Placebo
Intervention description: Active Substance: Lacosamide Pharmaceutical Form: Syrup Concentration: 10 mg/mL Route of Administration: oral; Active Substance: Placebo Pharmaceutical Form: Syrup Concentration: N/A Route of Administration: oral
Intervention MeSH terms: Lacosamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 255.0
Sex: All
Minimum age: 1 Month
Maximum age: 47 Months
Healthy volunteers: No
Keywords: Epilepsy; children; partial-onset seizures; lacosamide; LCM; pediatric

Summary:

      The purpose of this trial is to assess the efficacy, safety and tolerability 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.
    

Eligibility criteria:

        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 Syndrome, 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