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-ES
• Lead Sponsor: SK Life Science, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-13
• Last Update Posted: 18 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 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 5 years before Visit 1 that ruled out a progressive cause of epilepsy
5. For subjects new to Study YKP3089C040 during the 8 weeks prior to Visit 1, participants must have had at least 1 POS seizure. 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; 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 nerve stimulator [VNS] will be counted as one of the 3 allowed AEDs, with the settings stable for at least 4 weeks prior to screening and maintain stable throughout the study.
7. Investigator believes subject could benefit from new or continued exposure to study drug
8. Subjects 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 an 18-month history of felbamate use and a history of a fixed dosing regimen for a minimum of 60 days prior to Visit 1 (Screening/Baseline).
b. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.
c. 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.
3. Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1.
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, 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; 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. 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.
9. 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).
10. 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).
11. Subjects with Familial short QT syndrome
12. 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.
13. Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
14. 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.
15. History of AED-associated rash that involved conjunctiva or mucosae.
16. History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication.
17. Concomitant use of vigabatrin. Participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Visit 1 and with documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in a visual perimetry test.
18. 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/Baseline).
19. A VNS implanted less than 5 months before Visit 1 or changes in parameter less than 4 weeks before Visit 1 (or thereafter during the study)
20. History of or a concomitant medical condition that in the opinion of the investigator(s)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified