Dose-Escalation Study of Cenobamate (YKP3089) in Pediatric Subjects With Partial-Onset Seizures

Inclusion Criteria:

1. Diagnosis of epilepsy with partial-onset seizures (POS) with or without secondarilygeneralized seizures according to the International League Against Epilepsy's (ILAE)Classification of Epileptic Seizures). A diagnosis should have been established atleast 6 months prior to Visit 1 by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowsprovided that the participant meets the other diagnosis criterion (i.e., clinicalhistory, including a history of treatment failure with at least 2 AEDs)

2. Male or female subjects, from age 2 to less than 18 years at the time of informedconsent

3. Have a minimum weight of 10.0 kilograms (kg) (22.0 pounds [lb])

4. Written informed consent signed by the subject, legal guardian, or legallyauthorized representative (LAR) prior to entering the study in accordance with theICH GCP guidelines. Age appropriate assent will be obtained for children andadolescents. If the written informed consent is provided by the legal guardian orLAR because the subject is unable to do so, a written or verbal assent from thesubject must also be obtained

5. Are currently being treated with stable doses of 1 to a maximum of 2 approvedantiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before toVisit 1; in the case where a new AED regimen has been initiated for a participant,the dose must be stable for at least 8 weeks prior to Visit 1. A vagal nervestimulator (VNS) will not be counted as one of the 2 allowable AEDs

6. In the Investigator's opinion, parents or caregivers must be able to report accurateseizure assessments during the screening and study periods and subjects must be ableto ingest study drug

7. Subjects with an implanted vagal nerve stimulator will be allowed if the vagal nervestimulator was implanted at least 5 months prior to Visit 1 (Screening) and thestimulator parameters have not been changed for 30 days prior to Visit 1 and for theduration of the study

8. Subjects following a ketogenic diet will be allowed as long as the diet has beenstable for at least 30 days prior to Visit 1 (Screening) and will remain stable forthe duration of the study

Exclusion Criteria:

1. Progressive neurological disease, including degenerative CNS diseases andprogressive tumors

2. Evidence of clinically significant disease or any medical condition that wouldcompromise the subject's ability to safely complete the study including, but notlimited to, hepatic or renal failure, ischemic disease, human immunodeficiency virus (HIV) infection, active sexually transmitted disease (STD), active viral hepatitis,or malignancy

3. Positive urine screen of drugs of abuse (if not due to concomitant medication, e.g.,benzodiazepines as hypnotics) for Cohort 1 subjects.

4. History of anoxic episodes require resuscitation within 6 months before Visit 1,drug or alcohol dependency or abuse within approximately the last 2 years or use ofillegal recreational drugs.

5. Any surgical or medical condition that may interfere with the absorption,distribution, metabolism, or excretion of the investigational product

6. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, orsoda) or alcoholic beverages within 72 hours before Day 1 and 72 hours before theday of multiple dose PK sampling (Day 59 for Cohort I)

7. Consumption of grapefruit or grapefruit-containing products within 72 hours beforeDay 1 and 72 hours before the day of multiple dose PK sampling (Day 59 for Cohort I)

8. Significant clinical laboratory abnormalities, including elevation of serum AST orALT more than 2 times the upper limit or normal (ULN) for each age group.

9. Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 daysbefore Day 1

10. Scheduled for surgery during the study

11. Ketogenic diet or vagal nerve stimulation that has undergone alteration within 30days of Visit 1

12. Treatment with an investigational drug or device (other than VNS) ≤ 30 days beforeVisit 1

13. Females who are breastfeeding or pregnant at Screening or Baseline or who are ofreproductive age and do not agree to be abstinent or to use highly effective methodsof contraception

14. Current or history of pseudo-seizures (psychogenic nonepileptic seizures) withinapproximately 5 years before Visit 1

15. Have a history of status epilepticus that required hospitalization during the 6months before Visit 1

16. Have an unstable psychiatric diagnosis that may confound participants' ability toparticipate in the study or that may prevent completion of the protocol-specifiedtests (e.g., in the judgement of the investigator, pose an appreciable risk forsuicide, including suicidal behavior and ideation within 6 months before Visit 1,current psychotic disorder, acute mania)

17. Any suicidal ideation with intent or without a plan within 6 months before Visit 2in participants aged 6 and above.

18. Evidence of clinically significant disease (e.g., cardiac, respiratory,gastrointestinal, renal disease) that in the opinion of the investigator couldaffect the participant's safety or interfere with study assessments

19. Evidence of significant hematological disease; white blood cell (WBC) count equal orless than 2500/μL (2.50 1E+09/L) or an absolute neutrophil count equal or less than 1000/μL (1.00 1E+09/L)

20. Clinically significant electrocardiogram (ECG) abnormality, including prolongedcorrected QT interval (QTc) defined as greater than 450 msec or shortened correctedQT interval (QTc) defined as less than 350 msec

21. Subject has a history or 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.

22. History or AED-associated rash that involved conjunctiva or mucosae

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

24. Concomitant use of phenytoin and clobazam as these drugs may influence cenobamateplasma exposure. Subjects who took phenytoin or clobazam in the past must be offthese drugs for at least 30 days prior to Visit 1.

25. Concomitant use of vigabatrin. Participants who took vigabatrin in the past must beoff vigabatrin for at least 5 months before Visit 1 and with documentation showingno evidence of vigabatrin-associated clinically significant abnormality in a visualperimetry test

26. A history of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1- time rescue) more than twice within the 30 daysprior to Visit 1 (Screening)

27. A VNS implanted less than 5 months before Visit 1 or changes in parameter less than 30 days before Visit 1 (or thereafter during the study)

28. Presence of Familial short QT syndrome or relevant replicated QTc interval (QTcFless than 340 msec or greater than 450 msec in males and greater than 470 msec infemales) on electrocardiogram (ECG)