An Open-Label Study to Determine Safety , Tolerability, and Efficacy of Oral Lacosamide in Children With Epilepsy

Study Overview
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Brief Summary
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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.

Detailed Description
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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. In addition, the study is designed to provide continued availability of LCM to subjects who have completed the SP847 (NCT00938431) study and to subjects who have discontinued from SP847 (NCT00938431) and who, in the investigator's opinion, would benefit from long-term administration of LCM. SP848 will be open to subjects who have participated in other LCM pediatric clinical studies in epilepsy and will also be open to up to 100 subjects enrolling directly into SP848. Permissible LCM doses in SP848 are between 2-12 mg/kg/day (oral solution [syrup]) or the corresponding tablet dose up to a maximum dose of 600 mg/day. Subjects enrolled in SP848 have the option of remaining on the oral solution formulation of LCM or switching to the commercial tablet formulation, if feasible.

Official Title
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An Open-Label Study To Determine Safety, Tolerability And Efficacy Of Long -Term Oral Lacosamide (LCM) As Adjunctive Therapy In Children With Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Lacosamide
* Drug: Lacosamide


Participation Criteria
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Eligibility Criteria
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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: 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 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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 17 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>Subjects and their caregivers may chose to receive Lacosamide oral solution (syrup) or Lacosamide tablets. The maximum duration of LCM administration will be approximately 2 years. | Drug: Lacosamide<br>* 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)<br>* Other names: Vimpat®;Drug: Lacosamide<br>* 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.<br>* Other names: Vimpat®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | An AE is any untoward medical occurrence in a participant or clinical investigation study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration. | From Baseline to End of Safety Follow-Up (up to 4.3 years) | 
| Number of Participants With Serious Adverse Events (SAEs) | SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in participant hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment with parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above. | From Baseline to End of Safety Follow-Up (up to 4.3 years) | 
| Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event | TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration. | From Baseline to End of Safety Follow-Up (up to 4.3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period | Percent change in seizure frequency per 28 days (PCH) from the Baseline value (B) to Treatment Period interval (T) was defined as:PCH = [(SFT - SFB)/SFB] x 100 where, SFT corresponded to seizure frequency during Treatment Period for relative interval in open-label study and SFB corresponded to Baseline seizure frequency. For both periods, the frequency was standardized to the number of seizures per 28 days. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count case report form/electronic case report form (CRF/eCRF) module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. | From Baseline to End of Treatment Period (up to 4.2 years) | 
| Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency | A 50% responder is a participant experiencing a ≥50% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. | From Baseline to End of Treatment Period (up to 4.2 years) | 
| Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency | A 75% responder is a participant experiencing a ≥75% reduction in partial-onset seizure frequency per 28 days from Baseline to end of the specified time interval, otherwise a participant is a non-responder. For rollover participants, the Baseline values from the previous pediatric studies were designated as Baseline values in SP848. The Baseline value for seizure counts for directly enrolled participants were taken from the historical seizure count CRF/eCRF module in combination with the seizure diary data collected from the date of the Screening Visit to the day prior to the date of first dose of LCM. Participants from EP0060 RxL enrollment group had no baseline data due to taking oral LCM prior to EP0060. | From Baseline to End of Treatment Period (up to 4.2 years) | 
| Number of Seizure Days Per 28 Days for Participants With Generalized Seizures | A seizure day was defined as a day where any type of seizure was reported in the seizure diary and seizures were assessed. Days in the seizure diary which were marked as not done on the CRF/eCRF were not counted as seizure-free days. | Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96 | 
| Percentage of Participants Who Achieved a Seizure-free Status | Study participants were considered seizure-free for a given period if they completed the period, reported zero seizures during the period, and had no more than 10% of days in the period for which seizure data were not available (ie, not done was noted on the Seizure Frequency CRF/eCRF module). | From Baseline to End of Treatment Period (up to 4.2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lacosamide (VIMPAT)