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.

Study Overview
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Brief Summary
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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.

Detailed Description
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SP0966 is a Phase 2, multicenter, open-label exploratory study designed to assess the safety and preliminary efficacy of oral lacosamide as adjunctive therapy for epilepsy syndromes associated with generalized seizures in pediatric subjects ≥1 month to <18 years of age.

Official Title
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A MULTI-CENTER, OPEN-LABEL, EXPLORATORY STUDY TO INVESTIGATE THE SAFETY AND EFFICACY OF LACOSAMIDE AS ADJUNCTIVE THERAPY IN SUBJECTS ≥1 MONTH TO <18 YEARS WITH EPILEPSY SYNDROMES ASSOCIATED WITH GENERALIZED SEIZURES.

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lacosamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lacosamide<br> | Drug: Lacosamide<br>* 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.<br>* Other names: Vimpat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 to Visit 6 | The mean change in the count of generalized spike-wave discharges was presented. Visit 6 (Week 6) was the End of the Titration Period. | From Baseline (Day 1) to Visit 6 (Week 6) | 
| Mean Change in Days With Any Generalized Seizures (Absence, Myoclonic, Clonic, Tonic, Tonic-clonic, Atonic, Partial Evolving to Secondarily Generalized) Per 28 Days From the Baseline Period to the Maintenance Period (Approximately 24 Weeks) | The mean change in the count of days with generalized seizures was presented. | Baseline Period to the Maintenance Period (approximately 24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Changes in Count of 3 Hz Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory EEG From Visit 2 to Visit 6 | The mean change in the count of 3 Hertz (Hz) spike-wave discharges was presented. Visit 6 (Week 6) was the End of the Titration Period. | From Baseline (Day 1) to Visit 6 (Week 6) | 
| Number of Subject Withdrawals Due to Adverse Events From Baseline to End of Study (Approximately 32 Weeks) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. | From Baseline to End of Study (approximately 32 weeks) | 
| Number of Subjects Experiencing at Least 1 Treatment-emergent Adverse Event From Baseline to End of Study (Approximately 32 Weeks) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. | From Baseline to End of Study (approximately 32 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lacosamide, Vimpat, Epilepsy, Children