Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures

Inclusion Criteria:

1. Subject is male or female and aged ≥12 years.

2. Written informed consent signed by the subject or legal guardian, or legallyauthorized representative (LAR), prior to entering the study, in accordance with theInternational Conference on Harmonisation (ICH) Good Clinical Practice (GCP)guidelines. Age- appropriate assent will be obtained for adolescents. If the writteninformed consent is provided by the legal guardian because the subject is unable todo so, a written or verbal assent from the subject must also be obtained. Asrequired by country-specific regulations, only the subject may sign the InformedConsent Form (ICF) in accordance with ICH guidelines.

3. Female subjects of childbearing potential are willing to use an acceptable form ofbirth control

4. Subject has a clinical diagnosis of PGTC seizures (with or without other subtypes ofgeneralized seizures) in the setting of idiopathic generalized epilepsy.

5. Subject experiences at least 5 PGTC seizures in 12 weeks during thePre-Randomization Period.

6. Subject has had a routine electroencephalogram (EEG) within 5 years prior to Visit1 (Screening/Baseline) or during the Pre-Randomization Period withelectroencephalographic features consistent with idiopathic generalized epilepsy;other concomitant anomalies must be explained by adequate past medical history.

7. Subject has undergone computed tomography (CT) or magnetic resonance imaging (MRI)within 10 years prior to Visit 1 (Screening/Baseline) or during thePre-Randomization Period that ruled out a progressive cause of epilepsy.

8. Subject is currently receiving 1 to a maximum of 3 concomitant AEDs with fixeddosing regimens for a minimum of 30 days prior to Visit 1 (Screening/Baseline).

9. Benzodiazepines (except diazepam, see Exclusion Criterion No.7) taken at leastonce per week during the 30 days prior to Visit 1 (Screening/Baseline) forepilepsy, anxiety, or sleep disorder will be counted as 1 AED and the dosagemust be continued unchanged throughout the study. Therefore, only a maximum of 2 additional approved AEDs will be allowed. (See Exclusion Criterion No. 10 forintermittent benzodiazepine rescue parameters.)

10. Subjects receiving felbamate as a concomitant AED must meet the followingcriteria: i. Have a 2-year history of felbamate use and a history of a fixeddosing regimen for a minimum of 60 days prior to Visit 1 (Screening/Baseline).ii. No prior or known history of hepatotoxicity or hematologic disorder due tofelbamate.

11. Subject with an implanted vagal nerve or deep brain stimulator will be allowed ifthe stimulator was implanted at least 5 months prior to Visit 1 (Screening/Baseline)and the stimulator parameters are not changed for 30 days prior to Visit 1 and forthe duration of the study.

12. Subject taking a ketogenic diet will be allowed as long as the diet has been stablefor at least 3 months prior to Visit 1 (Screening/Baseline) and will remain stablefor 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. Subject has a history o f status epilepticus that required hospitalization within 12months prior to Visit 1 (Screening/Baseline).

3. Subject has PGTC seizure clusters where individual seizures cannot be counted orclassified.

4. Subject has a history of non-epileptic psychogenic seizures.

5. Subject has a concomitant diagnosis of Partial Onset Seizures (POS).

6. Subject has a clinical diagnosis of Lennox-Gastaut syndrome.

7. Subject is currently taking (within the 30 days prior to Visit 1 [Screening/Baseline]) any of the following medications: diazepam (for any reasonother than as intermittent benzodiazepine rescue medication), phenytoin,mephenytoin, fosphenytoin, phenobarbital, primidone, ethotoin, clopidogrel,fluvoxamine, amitriptyline, clomipramine, bupropion, methadone, ifosfamide,cyclophosphamide, or efavirenz.

8. Subject has participated in previous cenobamate clinical studies.

9. Subject has a history of vigabatrin use within 5months prior to Visit 1 (Screening/Baseline), or the subject plans to begin treatment with vigabatrin duringthe study. a) A subject with a history of vigabatrin use that ended more than 5 months prior toVisit1 may be enrolled after documented evidence of no vigabatrin-associatedclinically significant abnormality in an automated visual perimetry test.

10. Subject has a history of intermittent use of rescue benzodiazepines (i.e., 1 to 2doses over a 24-hour period is considered a 1-time rescue) 4 or more times withinthe 30 days prior to Visit 1 (Screening/Baseline).

11. Subject has received an investigational drug or device within 30 days prior to Visit 1 (Screening/Baseline).

12. Subject has a history of drug or alcohol dependency or abuse within 2 years prior toVisit 1 (Screening/Baseline).

13. Subject tests positive, via urine drug screen at Visit 1 (Screening/Baseline), forillicit drugs not legalized in your region/state, or for a drug that has not beenprescribed (e.g., certain opiates).

14. Subject has a history of any serious drug-induced hypersensitivity reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermalnecrolysis, or DRESS) or any drug-related rash requiring hospitalization.

15. History of AED-associated rash that involved conjunctiva or mucosae.

16. History of more than one non-serious drug-related hypersensitivity reaction thatrequired discontinuation of the medication.

17. Subject has evidence of clinically significant abnormalities or disease (e.g.,psychiatric, cardiac, respiratory, gastrointestinal, hepatic [aspartateaminotransferase (AST) or alanine aminotransferase (ALT) more than 2 times the upperlimit of normal (ULN), or total or direct bilirubin not more than ULN], or renaldisease) that, in the opinion of the Principal Investigator, could affect thesubject's safety or conduct of the study.

18. Presence of congenital short QT syndrome or relevant replicated change in QT/QTcinterval less than 340 msec on ECG.

19. Subject has any significant active Central Nervous System (CNS) infection,demyelinating disease, degenerative neurologic disease or any CNS disease deemed tobe progressive during the course of the study that may confound the interpretationof the study results.

20. Subject has a creatinine clearance less than 50 mL/min, as calculated byCockcroft-Gault equation.

21. Subject has an absolute neutrophil count less than 1500/µL.

22. Subject has platelet count lower than 80,000/µL in subjects treated with valproate.

23. Subject has a history of positive antibody/antigen test for hepatitis A, hepatitisB, hepatitis C, or HIV.

24. Subject has any suicidal ideation (with intent with or without a plan) at Visit 1 (Screening/Baseline) or Visit 4 (Randomization) (i.e., answering YES to Question 4and/or Question 5 on the Suicidal Ideation section of the C-SSRS).

25. Subject has more than 1 lifetime suicide attempt.

26. Subject is a staff member or immediate family member of study staff.

27. Previous exposure to cenobamate or sensitivity/allergy to components of the oralsuspension.

Any potential exception to the inclusion as well as exclusion criteria allowing de minimis (clinically trivial and meaningless) variations must be approved by the Medical Monitor.