An Open-Label Study to Determine Safety , Tolerability, and Efficacy of Oral Lacosamide in Children With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Lacosamide; Lacosamide
Intervention description: Lacosamide oral solution (syrup): Total daily dose between 2 mg/kg/day (1 mg/kg bid) to 12 mg/kg/day (6 mg/kg bid); Lacosamide tablets: Total daily dose between 100 mg (50mg bid) - 600mg (300 mg bid).
The maximum permissible dose of LCM will be 12 mg/kg/day or 600 mg/day.
Intervention MeSH terms: Lacosamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 366.0
Sex: All
Minimum age: 1 Month
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Lacosamide (VIMPAT)

Summary:

      SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in
      children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as
      adjunctive therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A signed informed consent form has been obtained from the parent/legal guardian and
             assent has been obtained from the subject, as required

          -  Subject and caregiver (which may be a parent, legal guardian, or other delegated
             caregiver) are willing and able to comply with all study requirements, including
             maintaining a daily seizure diary

        Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical
        studies in epilepsy must fulfill the following inclusion criteria:

          -  Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction
             or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or
             subject has participated in other LCM pediatric clinical studies in epilepsy

          -  Subject is expected to benefit from participation, in the opinion of the investigator

        Subjects who enroll directly into SP848 without previous participation in a LCM clinical
        study must fulfill the following inclusion criteria:

          -  Subject is >=4 years to <=17 years of age

          -  Subject has a diagnosis of epilepsy with partial-onset seizures

          -  Subject has been observed to have uncontrolled partial-onset seizures after an
             adequate course of treatment (in the opinion of the investigator) with at least 2
             Antiepileptic Drugs (AEDs) (concurrently or sequentially)

          -  Subject has been observed to have at least 2 countable seizures in the 4 week period
             prior to Screening

          -  Subject is on a stable dosage regimen of 1 to 3 AEDs

          -  Subject is an acceptable candidate for venipuncture

        Exclusion Criteria:

          -  Subject is receiving any investigational drugs or using any experimental devices in
             addition to Lacosamide (LCM)

          -  Subject >= 6 years of age has a lifetime history of suicide attempt, or has suicidal
             ideation in the past 6 months

        Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy
        are not permitted to enroll in the study if any of the following criteria are met:

          -  Subject meets either of the following:

               1. Withdrawal criteria for the primary study (with the exception of subjects who
                  discontinued due to a dose reduction or status epilepticus). For subjects
                  entering from EP0060, if the subject (or legal guardian) withdraws consent solely
                  due to route of LCM administration (iv) or if the subject requires more than 10
                  iv LCM infusions, the subject may be allowed to participant in SP848 after
                  discussion with and agreement from the Medical Monitor

               2. Ongoing serious Adverse Event (SAE)

                  Subjects who enroll directly into SP848 without previous participation in a LCM
                  clinical study are not permitted to enroll in the study if any of the following
                  criteria are met:

          -  Subject has ever received LCM

          -  Subject has any medical or psychiatric condition that, in the opinion of the
             investigator, could jeopardize or would compromise the subject's ability to
             participate in this study.

          -  Subject has a medical condition that could reasonably be expected to interfere with
             drug absorption, distribution, metabolism, or excretion

          -  Subject has a known hypersensitivity to any component of the investigational medicinal
             product

          -  Subject is a female of childbearing potential and does not practice an acceptable
             method of contraception for the duration of the study

          -  Subject has a creatinine clearance less than 30mL/min

          -  Subject has a clinically relevant ECG abnormality, in the opinion of the principal
             investigator (ie, second or third degree heart block at rest or a QT prolongation
             greater than 450ms)

          -  Subject has hemodynamically significant heart disease (eg, heart failure)

          -  Subject has an arrhythmic heart condition requiring medical therapy

          -  Subject has a known history of severe anaphylactic reaction or serious blood
             dyscrasias

          -  Subject has nonepileptic events, including psychogenic seizures, that could be
             confused with seizures. If both epileptic and nonepileptic events are present,
             epileptic events must be distinguished from nonepileptic phenomena

          -  Subject has a history of primary generalized epilepsy

          -  Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics.

          -  Subject has epilepsy secondary to a progressing cerebral disease or any other
             progressively neurodegenerative disease, such as Rasmussen syndrome

          -  Subject has a known sodium channelopathy, such as Brugada syndrome

          -  Subject has >2x upper limit of normal (ULN) of any of the following: alanine
             aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP),
             or >ULN total bilirubin (1.5xULN total bilirubin if known Gilbert's syndrome). If
             subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate
             bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin
             <35%)

        Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate
        LCM treatment are not permitted to enroll in the study if any of the following criteria are
        met:

        - Subjects have previously participated in a long-term, open-label LCM study