Study to Investigate Lacosamide as Add-on Therapy in Subjects ≥4 Years to <17 Years of Age With Partial Onset Seizures
Condition: Epilepsy
MeSH terms: Epilepsy; Seizures
Intervention: Lacosamide; Placebo
Intervention description: Subjects <30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day)
Subjects ≥30 kg to <50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)
Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day); Subjects <30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day)
Subjects ≥30 kg to <50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)
Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)
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: 404.0
Sex: All
Minimum age: 4 Years
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Lacosamide; Vimpat; UCB; Epilepsy; Partial Onset Seizures; Pediatric

Summary:

      Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other
      Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to <17 years of age who currently
      have uncontrolled partial onset seizures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
             written Informed Consent form is signed and dated by the parent(s) or legal
             representative. The Informed Consent form or a specific Assent form, where required,
             will be signed and dated by minors

          -  Subject/legal representative is considered reliable and capable of adhering to the
             protocol (eg, able to understand and complete diaries), visit schedule, and medication
             intake according to the judgment of the investigator

          -  Subject is male or female from ≥4 years to <17 years of age

          -  Subject has a diagnosis of Epilepsy with partial-onset seizures. The results of ≥1
             prior electroencephalogram (EEG) AND 1 prior magnetic resonance imaging/computerized
             tomography scan should be consistent with the above diagnosis

          -  Subject has been observed to have uncontrolled partial-onset seizures after an
             adequate course of treatment (in the opinion of the investigator) with ≥2
             Anti-Epileptic Drugs (AEDs) (concurrently or sequentially)

          -  Subject must have been observed to have on average ≥2 partial onset seizures per 28
             days with seizure free phase no longer than 21 days in the 8 week period prior to
             entry into the Baseline Period. During this study, subjects must have reported ≥2
             partial onset seizures during the 8 week prospective Baseline Period to be eligible
             for randomization at Visit 2. (Note: In the case of simple partial onset seizures,
             only those seizures with motor signs will be counted towards meeting the inclusion
             criterion.)

          -  Subject is on a stable dosage regimen of 1 to ≤3 AEDs. The daily dosage regimen of
             concomitant AED therapy must be kept constant for a period of ≥4 weeks prior to the
             Baseline Period

          -  Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED.
             The VNS device must be implanted for ≥6 months before Visit 1, and the device settings
             must be stable for ≥4 weeks before Visit 1 and be kept stable during the Baseline
             Period. Use of the VNS device magnet is allowed

        Exclusion Criteria:

          -  Subject has previously participated in this study or subject has been assigned to
             Lacosamide (LCM) in a previous LCM study

          -  Subject has participated in another study of an investigational medicinal product
             (IMP) or a medical device within ≤2 months of Visit 1 or is currently participating in
             another study of an IMP or a medical device

          -  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 ≥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 component of the IMP or has ever received
             LCM

          -  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 defined as those that result in a failure rate of less than 1% per year when
             used consistently and correctly), unless sexually abstinent, for the duration of the
             study. 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 WHO recommendation (ie, depot
             medroxyprogesterone acetate, norethisterone enantate, intrauterine devices, combined
             injectables, and progestogen implants) with administration of 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 a medical condition that could be expected in the opinion of the
             investigator to interfere with drug absorption, distribution, metabolism, or excretion

          -  Subject has experienced febrile seizures exclusively. The occurrence of febrile
             seizures in addition to other unprovoked seizures is not exclusionary

          -  Subject is on a ketogenic or other specialized diet. If the subject was on a
             specialized diet in the past, they must be off the diet for ≥2 months prior to the
             Baseline Period

          -  Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
             total bilirubin level ≥2 times the upper limit of normal (ULN), or creatinine
             clearance less than 30 mL/min

          -  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]
             greater than 450 ms)

          -  Subject has hemodynamically significant congenital heart disease

          -  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 that could be confused with seizures

          -  Subject has a current diagnosis of Lennox-Gastaut syndrome, primary generalized
             epilepsy, mixed seizure disorder (partial and primarily generalized seizures), or
             purely nocturnal seizures

          -  Subject has a history of convulsive status epilepticus ≤2 months prior to the Baseline
             Period

          -  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 <12 months are excluded. Note: any subject who has been
             treated with felbamate for ≥12 months and has not experienced serious toxicity issues
             is eligible

          -  Subject has a medically documented history of alcohol or drug abuse

          -  Subject has a known cardiac sodium channelopathy, such as Brugada syndrome

          -  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)