Open-Label Safety and Efficacy Study of Cenobamate (YKP3089) in Children with Partial-onset (Focal) Seizures

Phase 1

Conditions: partial onset (focal) seizures
MedDRA version: 21.1Level: LLTClassification code 10016843Term: Focal seizuresSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10061334Term: Partial seizuresSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0Level: LLTClassification code 10039910Term: SeizuresSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Psychiatry and Psychology [F] - Psychological processes [F02]

Registration Number: EUCTR2020-005344-27-DE

Lead Sponsor: SK Life Science, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 140

Inclusion Criteria

1. Have a diagnosis of epilepsy with partial-onset (focal) seizures (POS) with or without secondarily generalized seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures. A diagnosis should have been established at least 12 months prior to Visit 1 (Screening) by clinical history and an
electroencephalogram (EEG) that is consistent with the diagnosis;
normal interictal EEGs will be allowed provided that the participant
meets the other diagnosis criterion (i.e., clinical history)
2. Male or female participant, from age 2 to less than 18 years at the
time of informed consent/assent (dates including informed consent in YKP3089C039)
3. Have a minimum weight of 10.0 kilograms (kg) (27.0 pounds [lb])
4. Have had a brain imaging (e.g., magnetic resonance imaging [MRI]
scan or computed tomography (CT) within 10 years before Visit 1
(Screeining) that ruled out a progressive cause of epilepsy
5. For subjects new to Study YKP3089C040 participants must have had at least 1 POS seizure during the 28-day Baseline Period. Only simple POS with motor signs, complex POS, and complex POS with secondary generalization are counted toward this inclusion for POS
6. Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit 1 (Screening). A vagal nerve stimulator [VNS] will not be counted as one of the 3 allowed AEDs, but the settings should be stable for at least 4 weeks prior to Visit 1 (Screening).
7. Investigator believes subject could benefit from new or continued
exposure to study drug
8. Subjects entering from study YKP3089C039 must continue to meet all of the inclusion criteria from the YKP3089C039 study
9. Subjects receiving felbamate as a concomitant AED must meet the
following criteria:
a. Have a 12-month history of felbamate use and a history of a fixed
dosing regimen for a minimum of 60 days prior to Visit 1 (Screening).
b. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.
10. Subjects following a ketogenic diet will be allowed as long as the diet has been stable for at least 30 days prior to Visit 1 (Screening) and will remain stable for the duration of the study
Any potential exception to inclusion criteria allowing de minimis
(clinically trivial and meaningless) variations must be approved by the
medical monitor.
Are the trial subjects under 18? yes
Number of subjects for this age range: 140
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Females who are breastfeeding or pregnant at Screening or Baseline
2. Current or history of pseudo-seizures (psychogenic nonepileptic
seizures) within approximately 2 years before Visit 1 (Screening).
3. Have a history of status epilepticus that required hospitalization
during the 6 months before Visit 1 (Screening).
4. Have an unstable psychiatric diagnosis that may confound
participants' ability to participate in the study or that may prevent
completion of the protocol-specified tests (e.g., significant suicide risk, including suicidal behavior and ideation within 6 months before Visit 1 (Screening), current psychotic disorder, acute mania).
5. Any suicidal ideation with intent with or without a plan within 6
months before Visit 2 (i.e., answering Yes to questions 4 or 5 on the
Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) in participants aged 6 and above.
6. Are scheduled and/or confirmed to have epilepsy surgery within 6
months after Visit 1 (Screening); however, those who have previously
documented failed epilepsy surgery will be allowed.
7. Evidence of clinically significant disease (e.g., cardiac, respiratory,
gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
8. Presence of only nonmotor simple partial seizures or primary
generalized epilepsies.
9. Evidence of moderate or severe renal insufficiency as defined by
estimated glomerular filtration rates (eGFRs) of 31 to < 60 milliliters
per minute (mL/min) and < 30 mL/min, respectively.
10. Evidence of significant active hepatic disease. Stable elevation of
liver enzymes, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) due to concomitant medication(s), will be
allowed if they are less than 3 times the upper limit of normal (ULN).
11. Evidence of significant active hematological disease; white blood cell (WBC) count equal or less than 2500/µL (2.50 1E+09/liter [L]) or an absolute neutrophil count equal or less than 1000/µL (1.00 1E+09/L).
12. Subjects with Familial short QT syndrome
13. Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than 450 milliseconds (msec) or shortened corrected QT interval (QTc) defined as less than 340 msec.
14. Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
15. Subject has a history of any serious drug-induced hypersensitivity
reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or DRESS) or any drug-related rash requiring hospitalization.
16. History of AED-associated rash that involved conjunctiva or mucosae.
17. History of more than one non-serious drug-related hypersensitivity
reaction that required discontinuation of the medication.
18. Concomitant use of vigabatrin. Participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Visit 1
(Screeining) and with documentation showing no evidence of a
vigabatrin-associated clinically significant abnormality in a visual
perimetry test.
19. 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 once within the 30 days prior to Visit 1 (Screening).
20. A VNS implanted less than 5 months before Visit 1 (Screening) or
changes in parameter less

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of cenobamate in pediatric subjects 2<18 years of age with partial-onset (focal) seizures;Secondary Objective: • To evaluate the efficacy of cenobamate in pediatric subjects with<br>partial onset (focal) seizures<br>• To collect plasma samples to support the evaluation of the<br>pharmacokinetics (PK) of cenobamate in pediatric subjects with partial<br>onset (focal) seizures administered with tablets or suspension<br>• To collect plasma samples to support the evaluation of the<br>PK/pharmacodynamics (PD) of cenobamate in pediatric subjects with<br>partial onset (focal) seizures<br>• Acceptability and palatability assessment (determined by a 5-point<br>Hedonic Scale) of the oral formulation and tablets – Day 1, and Day 15. ;Primary end point(s): Number of participants with any treatment-emergent adverse event (TEAE) and any serious adverse event (SAE) during the first year of exposure;Timepoint(s) of evaluation of this end point: 1 Year

Secondary Outcome Measures

Name	Time	Method

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