partial-onset seizures

The primary objective of this study is to evaluate the efficacy of LCM administered concomitantly with 1 to 3 AEDs in subjects ≥1 month to <4 years of age with epilepsy who currently have uncontrolled partial-onset seizures. The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥1 month to <4 years of age with epilepsy who currently have uncontrolled partial-onset seizures. An additional objective is to evaluate the PK of LCM in children ≥1 month to <4 years of age.

VIMPAT® Lacosamide

(R)-2-acetamido-N-benzyl-3methoxypropionamide

syrup

10

For the US:
the primary efficacy variable will be the contingent on the percentage of subjects that
discontinue from the study after the first dose of the study medication but prior to
performance of the 72-hour End-of-Maintenance Period video-EEG (ie, early
discontinuation).
The following variable will be considered primary for the US given that ≤10% of subjects
discontinue early from the study.
• The change in ADF of electrographic partial-onset seizures as measured on the
72-hour End-of-Maintenance Period video-EEG compared to the 72-hour
End-of- Baseline Period video-EEG
If >10%subjects discontinue early from the study, the following contingency endpoint will be
considered primary for the US (same as the primary efficacy variable for the EU):
• The proportion of responders where a responder is a subject experiencing a 50% or
greater reduction in their ADF of electrographic partial-onset seizures recorded on the
72-hour End-of Maintenance Period video-EEG compared to the 72-hour End-ofBaseline Period video-EEG.
For the EU:
The primary efficacy variable will be the proportion of responders where a responder is a
subject experiencing a 50% or greater reduction in their ADF of electrographic partial-onset
seizures recorded on the 72-hour End-of-Maintenance Period video-EEG compared to the 72-
hour end of Baseline Period video-EEG.

Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. 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(s)/caregiver(s) (in accordance with local regulation)
2. Subject’s parent(s) or legal representative(s)/caregiver(s) is considered reliable and
capable of adhering to the protocol visit schedule or medication intake according to
the judgment of the investigator
3. Subject is male or female from ≥1 month (ie, 4 weeks after full term [37 weeks
gestational age]) to <4 years of age. For preterm infants <1 year old, the corrected
gestational age should be used when determining eligibility. The generally accepted
definition of corrected gestational age, which is calculated by subtracting the number
of weeks born before 37 weeks of gestation from the chronological age, will be used
for this study
4. Subject has a diagnosis of epilepsy with partial-onset seizures. The results of ≥1 prior
EEG and ≥1 magnetic resonance imaging/computerized tomography scan should be
consistent with this diagnosis
5. Subject weighs >4 kg to <30kg at Visit 1
6. Subject has uncontrolled partial-onset seizures after an adequate course of treatment
(in the opinion of the investigator) with ≥2 AEDs (concurrently or sequentially)
7. Subject has experienced at least ≥2 partial-onset seizures with or without secondary
generalization during each consecutive 7-day period during the 2 weeks prior to
Visit 1
8. Subject has at least ≥2 partial-onset seizures with or without secondary generalization
during the 72-hour Baseline Video-EEG
9. Subject is on a stable (concurrently or sequentially) dosage regimen of 1 to 3 AEDs.
The dosage regimen of concomitant AED therapy must be kept constant for a period
of ≥ 2 weeks prior to Visit 1. A stable daily dosage regimen of a concomitant
benzodiazepine (BZD) will be considered as a concomitant AED
10. Vagus nerve stimulation is allowed and will not be counted as a concomitant AED.
The VNS device must have been implanted for ≥6 months prior to Visit 1; device
settings must be kept at a stable setting for ≥2 weeks prior to Visit 1 and kept stable
during the Baseline, Treatment and Transition Periods. Use of the VNS device magnet
is allowed
11. Subject is an acceptable candidate for venipuncture.

Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject has previously participated in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP)
or a medical device during the 2 months immediately prior to Visit 1 or is currently
participating in another study of an IMP or a medical device
3. 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
4. Subject has been previously treated with LCM
5. Subject has a known hypersensitivity to any component of the study medication
6. Subject has a medical condition that could be expected, in the opinion of the
Investigator, to interfere with study medication absorption, distribution, metabolism,
or excretion
7. Subject has experienced febrile seizures exclusively. The occurrence of febrile
seizures in addition to partial-onset seizures is not exclusionary
8. Subject is on a ketogenic or other specialized diet for the treatment of epilepsy. If the
subject was on a ketogenic or other specialized diet in the past, they must be off this
diet for ≥2 months prior to Visit 1
9. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
total bilirubin level ≥2 times the upper limit of normal (ULN), or creatinine clearance
<30mL/min
10. 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)
prolongation greater than 450ms)
11. Subject has a hemodynamically significant congenital heart disease
12. Subject has an arrhythmic heart condition requiring medical therapy
13. Subject has a known history of severe anaphylactic reaction secondary to medication
intake or serious blood dyscrasias
14. Subject has nonepileptic events that could be confused with seizures. Subjects may be
included if epileptic events can be clearly distinguished and the frequency meets the
study inclusion criteria
15. Subject has a current diagnosis of Lennox-Gastaut syndrome, epilepsia partialis
continua, primary generalized epilepsy, or seizures that are not of partial-onset origin
16. Subject has a history of status epilepticus ≤2 months prior to Screening (Visit 1)
17. Subject has been treated with ethosuximide
18. Subject is currently being treated with vigabatrin or has discontinued use <12 months
prior to Visit 1. Subjects who were previously treated with vigabatrin and have
discontinued use >12 months prior to Visit 1 are eligible
19. 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. Subjects treated with felbamate for ≥12
months prior to Visit 1 and who have not experienced serious toxicity issues are
eligible
20.Subject has an acute or subacutely 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)
21. Subject has a known sodium channelopathy, such as Brugada syndrome