| Eligibility |
Inclusion Criteria:
Eligible subjects must meet all of the following criteria to be enrolled in the study:
1. Male or female subject and age 18 to 70 years inclusive at the time of signing the
informed consent
2. Weight at least 35 kg
3. Written informed consent signed by the subject prior to entering the study in
accordance with the ICH GCP guidelines. For subjects who lack the capacity, consent
will be obtained from the parent/legal guardian. For all underaged subjects according
to the specific laws of the country, both the written consent of the subject and the
consent of the parent/legal guardian will be obtained.
4. A diagnosis of partial onset seizures according to the International League Against
Epilepsy's Classification of Epileptic Seizures (1981). Diagnosis should have been
established by clinical history and an electroencephalogram (EEG).
5. EEG performed within 5 years prior to Visit 1 that is consistent with localization
related epilepsy; normal interictal EEGs will be allowed provided that the subject
meets the other diagnosis criterion (i.e., clinical history). For chronic patients for
which the current diagnosis is not very clear, additional EEG results older than 5
years but within 10 years may be used for final confirmation of epilepsy diagnosis.
6. Need additional antiepileptic drug (AED) treatment despite having been treated with at
least one AED for the last 2 years.
7. During the 8-week Screening/Baseline Period, subjects must have at least 8 partial
seizures including only simple partial seizures with motor component, complex partial
seizures, or secondarily generalized seizures without a seizure-free interval of
greater than 25 days any time during the 8-week period. Subjects must have at least 3
of these partial seizures during each of the two consecutive 4-week segments of the
Screening/Baseline Periods, respectively.
8. Currently on stable antiepileptic treatment regimen:
1. Subject must have been receiving stable doses of 1 to 3 AEDs for at least 4 weeks
prior to Visit 1 to be continued unchanged throughout the Double-blind Treatment
Period.
2. Vagal nerve stimulator (VNS) or deep brain stimulator (DBS) will not be counted
as an AED; however, the parameters must remain stable for at least 4 weeks prior
to Visit 1 and during the study. VNS or DBS must have been implanted at least 5
months prior to Visit 1.
3. The daily use of benzodiazepines (except for diazepam) for epilepsy, or for
anxiety or sleep disorder, will be counted as 1 AED and must be continued
unchanged throughout the study. Therefore, only a maximum of 2 additional
approved AEDs will be allowed.
4. Subjects receiving felbamate as a concomitant AED must meet the following
criteria:
i. Two-year history of felbamate use and a history of a fixed dosing regimen for a
minimum of 60 days prior to Visit 1 ii. No prior or known history of hepatotoxicity or
hematologic disorder due to felbamate
9. Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the
past 5 years that ruled out a progressive cause of epilepsy. If brain imaging has not
been performed within the past 5 years, a CT scan must be performed prior to
randomization. For chronic patients for which the current diagnosis is not very clear,
additional CT or MRI results older than 5 years but within 10 years may be used for
final confirmation of epilepsy diagnosis.
10. Ability to reach subject by telephone
11. Use of an acceptable form of birth control by female subjects of childbearing
potential
12. Subject taking a ketogenic diet will be allowed as long as the diet has been stable
for at least 3 months prior to Visit 1 and will remain stable for the duration of the
study.
Exclusion Criteria:
1. Female subjects who are pregnant (or planning to become pregnant during the study),
lactating or breast-feeding
2. History of non-epileptic or psychogenic seizures
3. Presence of only non-motor simple partial seizures or primary generalized epilepsies
4. History of seizure clusters (episodes lasting less than 30 minutes in which multiple
seizures occur with such frequency that the initiation and completion of each
individual seizure cannot be distinguished) within 6 months prior to Visit 1
5. Presence or previous history of Lennox-Gastaut syndrome
6. Scheduled epilepsy surgery within 8 months of Visit 1
7. Evidence of any clinically significant laboratory abnormalities or disease (e.g.,
psychiatric, behavioral problems, cardiac, respiratory, gastrointestinal, hepatic
[liver transaminases, ALT or AST, more than twice the upper limit of normal (ULN) or
total or direct bilirubin not within normal limits], or renal disease) that, in the
opinion of the Investigator, could affect subject's safety or conduct of the study.
8. Any clinically significant active central nervous system (CNS) infection,
demyelinating disease, degenerative neurologic disease, or any CNS disease deemed to
be progressive during the course of the study that may confound the interpretation of
the study results
9. Presence of psychotic disorders and/or unstable recurrent affective disorders evident
by use of antipsychotics; presence or recent history (within 6 months) of major
depressive episode
10. Use of intermittent rescue benzodiazepines more than once per month (1 to 2 doses in a
24-hour period is considered as 1 rescue) in the 1-month period prior to Visit 1
11. Current or recent use (within 30 days prior to Visit 1) of any of the following
medications: diazepam/phenytoin/phenobarbital (or metabolites of these drugs),
clopidogrel, fluvoxamine, amitriptyline, clomipramine, bupropion, methadone,
ifosfamide, cyclophosphamide, efavirenz, natural progesterone, or traditional
Chinese/herbal medicines indicated for neurological system
12. Current or recent (within 5 months prior to Visit 1) use of vigabatrin or ezogabine.
Subjects with a prior history of treatment with vigabatrin must have documentation
showing no evidence of a vigabatrin associated clinically significant abnormality in a
visual perimetry test. Subjects with a prior history of treatment with ezogabine
should have no evidence of retinal abnormalities with funduscopic features similar to
those seen in retinal pigment dystrophies.
13. Previous exposure to cenobamate
14. Participation in any other trials involving an investigational product or device
within 30 days prior to Visit 1
15. History of alcoholism, drug abuse, or drug addiction within the past 2 years prior to
Visit 1 as assessed by the Investigator
16. History of status epilepticus within 3 months of Visit 1
17. History of any serious drug-induced hypersensitivity reaction (including but not
limited to Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with
eosinophilia and systemic symptoms [DRESS]) or any drug-related rash requiring
hospitalization
18. History of AED-associated rash that involved conjunctiva or mucosae
19. History of any drug-related hypersensitivity reaction that required discontinuation of
the medication
20. Presence of Familial short QT syndrome or relevant replicated QTc interval (QTcF less
than 340 msec or greater than 450 msec in males and greater than 470 msec in females)
on electrocardiogram (ECG)
21. Absolute neutrophil count less than 1,500/µL
22. Platelet counts lower than 80,000/µL in subjects treated with VPA
23. Creatinine clearance less than 60 mL/min, as calculated by Cockcroft-Gault equation
24. History of positive test results for HBsAg, HCV-Ab, and HIV-Ab
25. More than 1 lifetime suicide attempt
26. A "YES" answer to Question 1 or 2 of the C-SSRS (Baseline/Screening version) Suicidal
Ideation section in the past 6 months or a "YES" answer to any of the Suicidal
Behavior Questions in the past 2 years
27. Subject is a staff member or immediate family member of study staff.
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