A Study to Investigate the Safety and Efficacy of Lacosamide Added to the Patients Current Therapy in Patients Aged 1 Month to Less Than 18 Years Old With Epilepsy Syndromes Associated With Generalized Seizures.
Condition: Epilepsy
MeSH terms: Epilepsy; Seizures; Epileptic Syndromes
Intervention: Lacosamide
Intervention description: Oral intake twice daily of tablet (100 mg or 50 mg) or syrup formulation (10 mg/ml).
Total daily dose will be titrated over a period of 6 weeks with starting dose of 100 mg/day or 2 mg/kg/day up to doses not exceeding 600 mg/day or 12 mg/kg/day tablet or syrup, respectively. Followed by a 12 week maintenance period with stable dosing of at least 200 mg/day or 4 mg/kg/day tablet or syrup, respectively.
Intervention MeSH terms: Lacosamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 1 Month
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Lacosamide; Vimpat; Epilepsy; Children

Summary:

      SP0966 is an exploratory study to investigate safety and efficacy of Lacosamide (LCM) in
      children with epilepsy syndromes associated with generalized seizures. LCM will be added to
      current antiepileptic treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A signed informed consent has been obtained from the parent/legal representative and
             assent has been obtained from the subject (when possible)

          -  Subject and caregiver are willing and able to comply with all study requirements
             including maintaining a daily seizure diary

          -  Subject is male or female, ≥1 month to <18 years of age

          -  Subject has a diagnosis of uncontrolled epilepsy with generalized seizures (Type II)
             according to the International Classification of Epileptic Seizures (1981). The
             underlying epilepsy syndrome should be documented. Diagnosis should have been
             established by clinical history and an Electroencephalogram (EEG) with generalized
             spike-wave discharges. Documentation of the EEG finding of generalized spike waves
             (EEG recording or a report) is required. The EEG should have been performed no more
             than 18 months prior to Visit 1 (with no change to diagnosis or seizure types during
             this time)

          -  Subject must have experienced 2 or more events (typical generalized seizures
             associated with diagnosed epilepsy syndrome) within the 6-week prospective Baseline
             Period

          -  Subject is on a stable dosage regimen of 1 to 3 antiepileptic drugs (AEDs). The daily
             dosage regimen of concomitant AED therapy must be kept constant for a period of at
             least 4 weeks prior to the Baseline Period

          -  Vagal nerve stimulation is allowed and will not be counted as a concomitant AED. The
             vagus nerve stimulation (VNS) device must be implanted for at least 6 months before
             Visit 1, and the device settings must be stable for at least 4 weeks before Visit 1
             and be kept stable during the Baseline Period and the Treatment Period. Use of the VNS
             device magnet is allowed

          -  Body weight at Visit 1 is at least 4 kg for infants.

          -  Females of childbearing potential must have a negative pregnancy test at Visit 1

          -  Subjects with West Syndrome are eligible if Baseline EEG demonstrates hypsarrhythmia
             despite treatment with at least 2 AEDs appropriate for the treatment of this syndrome

        Exclusion Criteria:

          -  Subject has previously participated in this study, subject has been assigned to
             Lacosamide (LCM) in a previous LCM study, or subject has ever received LCM

          -  Subject is currently participating or has participated within the last 2 months in any
             study of an investigational drug or experimental device

          -  Subject has a history of convulsive status epilepticus within 1 month prior to Visit 1

          -  Subject has a current or previous diagnosis of pseudoseizures, conversion disorders,
             or other nonepileptic ictal events that could be confused with seizures

          -  Subject has exclusively typical absence (Type IIA1) or atypical absence (Type IIA2)
             seizures (no other generalized seizure types are reported), or has only partial-onset
             seizures (Type I)

          -  Subject has any medical or psychiatric condition that, in the opinion of the
             investigator, could jeopardize the subject's health or would compromise the subject's
             ability to participate in this study

          -  Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual
             attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the
             past 6 months as indicated by a positive response ("Yes") to either Question 4 or
             Question 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening

          -  Subject has a known hypersensitivity to any components of the investigational
             medicinal product (IMP)

          -  Subject has a medical condition that could reasonably be expected to interfere with
             drug absorption, distribution, metabolism, or excretion

          -  Subject has a known history of severe anaphylactic reaction or serious blood
             dyscrasias

          -  Subject has any history of alcohol or drug abuse within the previous 2 years

          -  Subject has an acute or sub-acutely 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 alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total
             bilirubin levels ≥2x the upper limit of normal (ULN) or has alkaline phosphatase
             levels ≥3x ULN

          -  Subject has impaired renal function (ie, creatinine clearance is lower than 30 mL/min)
             at Visit 1

          -  Subject has sick sinus syndrome without a pacemaker, or second or third degree
             atrioventricular (AV) block

          -  Subjects with second- or third-degree heart block are excluded from SP0966
             (NCT01969851), without the requirement of being at rest

          -  Subject has hemodynamically significant heart disease (eg, heart failure)

          -  Subject has an arrhythmic heart condition requiring medical therapy

          -  Subject has a known cardiac sodium channelopathy, such as Brugada syndrome

          -  Female subject who is pregnant or nursing, and/or a female subject of childbearing
             potential who is not surgically sterile or does not practice 1 highly effective method
             of contraception (according to International Conference on Harmonisation [ICH]
             guidance. Female subject of childbearing potential taking enzyme inducing
             antiepileptic drugs(EI AEDs) (carbamazepine, phenytoin, barbiturates, primidone,
             topiramate, oxcarbazepine) who is not surgically sterile or does not practice 1 highly
             effective method of contraception according to the World Health Organization
             recommendation (ie, depot medroxyprogesterone acetate, norethisterone enantate,
             intrauterine devices, combined injectables, and progestogen implants) with
             administration of enzyme inducing antiepileptic drugs (EI-AEDs) or does not practice 2
             combined methods of contraception (ie, combined hormonal contraception plus barrier
             method with spermicidal agent), unless sexually abstinent, for the duration of the
             study

          -  Subject has been treated with vigabatrin and experienced any vision loss. Subjects who
             have received vigabatrin in the past must have documentation of an assessment for
             vision loss prior to study entry or documentation of why visual field testing cannot
             be performed

          -  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 less than 12 months are excluded. Note: any subject who has
             been treated with felbamate for at least 12 months and has not experienced serious
             toxicity issues is eligible

          -  Subject is taking monoamine oxidase (MAO) inhibitors or narcotic analgesics.

          -  Subject is on a ketogenic or other specialized diet. If he/she was on a specialized
             diet in the past, he/she must be off the diet for at least 2 months prior to the
             Screening Visit (Visit 1)

          -  Subject has primary generalized tonic-clonic seizures with a diagnosis of idiopathic
             generalized epilepsy