Partial onset (focal) seizures MedDRA version: 26.1 Level: LLT Classification code 10016843 Term: Focal seizures System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10061334 Term: Partial seizures System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10039910 Term: Seizures System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Cenobamate
Product Name: Cenobamate
Product Code: YKP3089
Pharmaceutical Form: Tablet
INN or Proposed INN: CENOBAMATE
CAS Number: 913088-80-9
Current Sponsor code: YKP3089
Concentration un
Sponsors
SK Life Science, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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) (22.0 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 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 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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 (Screening) 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 or changes in parameter less than 4 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 partial onset (focal) seizures • To collect plasma samples of cenobamate to support the evaluation of the pharmacokinetics (PK) of cenobamate in pediatric subjects with partial onset (focal) seizures administered with tablets or suspension • To collect plasma samples of cenobamate to support the evaluation of the PK/pharmacodynamics (PD) in pediatric subjects with partial onset (focal) seizures • Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral suspension 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percent change in seizure frequency over 28 days during the maintenance phase 2. Number of participants who are seizure-free during the treatment period and during each phase of the study 3. Percentage of responders (25%, 50%, and 75% responders) during the treatment period and during each phase of the study 4. Change from Baseline in A-B neuropsychological assessment schedule (ABNAS) end of titration, end of maintenance and 52 weeks 5. Change from Baseline in Child Behavior Checklist (CBCL) scores end of titration, end ofmaintenance and 52 weeks 6. Change from Baseline in Lafayette Grooved Pegboard Test (LGPT) scores end of titration, end of maintenance and 52 weeks 7. Change from Baseline in height 8. Change from Baseline in weight 9. Percentage of participants with any treatment-emergent reports of suicidal ideation and behavior assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) during treatment (adult version for 12-18-year olds; Pediatric version for 6-11 year olds) 32 10. Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral suspension and tablets Visit 2and Visit 3.;Timepoint(s) of evaluation of this end point: 52 weeks of treatment followed by follow up visit and titrating off of study medication | — |
Countries
Australia, Germany, Hungary, Korea, Republic of, Poland, Spain, United States
Contacts
Public ContactMarc Kamin, MD
SK Life Science Inc
Outcome results
None listed