idiopathic generalized epilepsy

The primary study objective is to demonstrate the efficacy of oral LCM vs placebo as adjunctive therapy for uncontrolled PGTC seizures in subjects with IGE currently taking 1 to 3 concomitant AEDs independent of the number of prior failed AEDs The secondary study objective is to assess the safety and tolerability of LCM in subjects with IGE with uncontrolled PGTC seizures.

VIMPAT® Lacosamide

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

syrup, Film-coated Tablet

10 mg/mL,50 mg tab

Primary efficacy variable
The primary efficacy variable is the time to the second PGTC seizure during the 24-week
Treatment Period.

Secondary efficacy variables
The key secondary efficacy variable is:
 Seizure freedom for PGTC seizures for the 24-week Treatment Period
The other secondary efficacy variables are:
 The percent change in PGTC seizure frequency per 28 days from the Combined Baseline
(combined 12-week Historical and 4-week Prospective Baseline) to the first 6 weeks of the
Treatment Period
 The percent change in PGTC seizure frequency per 28 days from Combined Baseline to the
24-week Treatment Period
 Time to the first PGTC seizure during the 24-week Treatment Period

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/Assent Form is signed and dated by the subject or 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.
2. 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.
3. Male and female subjects ≥4 years of age.
4. Subject with a confirmed diagnosis at least 24 weeks prior to Visit 1 and a disease onset
prior to 30 years of age, consistent with IGE experiencing PGTC seizures (Type IIE) that are
classifiable according to the ILAE Classification of Epileptic Seizures (ILAE, 1981).
5. Subject has ≥3 PGTC seizures during the 16-week Combined Baseline (12-week Historical
Baseline plus 4-week Prospective Baseline) distributed as described below:
 ≥2 PGTC seizures during the 12-week Historical Baseline with ≥1 PGTC seizure during
first 8 weeks of the Historical Baseline, and
 ≥1 PGTC seizure during the second 8 weeks of the Combined Baseline (ie, during the last
4 weeks of the Historical Baseline or during the 4-week Prospective Baseline)
6. If a brain magnetic resonance imaging (MRI)/computed tomography (CT) scan has been
performed, there must be no evidence of any progressive abnormality or any lesion likely to
be associated with partial-onset seizures.
7. Subject has been maintained on a stable dose regimen of 1 to 2 non-benzodiazepine marketed
AEDs OR 1 to 3 AEDs (with at least 1 AED identified as a benzodiazepine) for at least
28 days prior to Visit 1 with or without additional concurrent stable VNS (see Section 7.8).
 Vagus nerve stimulation must have been in place for at least 6 months prior to Visit 1
with constant settings for at least 28 days prior to Visit 1 and during the Prospective
Baseline and Treatment Period.
8. Subjects are required to have had an EEG report consistent with IGE (eg, generalized ≥3Hz
epileptiform discharges and a normal EEG background) confirmed by a Central Reviewer.

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 or subject has previously been assigned to
treatment in a study of LCM.
2. Subject has participated in another study of an investigational medicinal product (IMP) or an
experimental medical device within the last 30 days or is currently participating in another
study of an IMP or a medical device.
3. Subject has a history of partial-onset seizures or EEG findings indicative of partial-onset
seizures.
4. Subject has symptomatic generalized epilepsy ([ILAE, 1989] eg, Lennox-Gastaut Syndrome)
or evidence of both focal and generalized epilepsy.
5. Subject has a history of convulsive status epilepticus 1 year prior to Screening.
6. Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other
nonepileptic ictal events which could be confused with seizures.
7. 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.
8. Subject 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.
9. Subject has a known hypersensitivity to any components of the investigational product(s).
10. Subject has a medical condition that could reasonably be expected to interfere with drug
absorption, distribution, metabolism, or excretion.
11. Subject has multiple drug allergies or severe drug allergy.
12. Subject has any history of alcohol or drug abuse within the previous 2 years.
13. Subject has an acute or sub-acutely progressive central nervous system disease.
14. Subject with a known history of severe anaphylactic reaction or serious blood dyscrasias.
15. Subject has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total
bilirubin levels ≥2x the upper limit of normal (ULN) or has alkaline phosphatase levels
≥3xULN at Visit 1.
16. Subject has impaired renal function (ie, creatinine clearance [CLcr] is <30mL/min) at
Screening (see Section 10.6).
17. Subject has a known sodium channelopathy, such as Brugada syndrome.
18. Subject has sick sinus syndrome without a pacemaker, or second- or third-degree
atrioventricular (AV) block, or subject has any other clinically significant ECG
abnormalities.
19. Subject has experienced a myocardial infarction in the last 3 months prior to Visit 1.
20. Subject has New York Heart Association Class III or Class IV heart failure.
21. Female subject who is pregnant or nursing and/or a woman of childbearing potential who is
not surgically sterile, 2 years postmenopausal, 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 <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, 2 years postmenopausal, 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 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.
22. Subject has been taking 1 or more of the following medications on a regular basis within
28 days prior to Visit 1: neuroleptics, monoamine oxidase (MAO) inhibitors, barbiturates (for
indications other than epilepsy), or narcotic analgesics.
23. Subject with concomitant treatment of felbamate or previous felbamate therapy within the
last 6 months prior to Visit 1.
24. Subject has taken vigabatrin in the preceding 6 months. Note: A subject with a history of
vigabatrin treatment must have had a visual perimetry test at least 6 months following
conclusion of treatment. The results of the visual perimetry test must have shown either no
damage or a visual field defect associated with 1 of the following 2 conditions: 1) there was
no change from a visual field test done at some point while the subject was taking vigabatrin,
or 2) there was no change from a visual field test done shortly after stopping vigabatrin
administration.
25. Subject is on a ketogenic diet.
If the investigator has any doubts concerning the subject’s eligibility, he/she should consult the
UCB Study Physician or representative for clarification.