Safety and Efficacy Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures

Korábbi kezelés

• Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1 (Screening).
• 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).
• 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, if able].
• 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.
• 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.
• 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).
• A VNS implanted less than 5 months before Visit 1 (Screening) or changes in parameter less than 4 weeks before Visit 1 (or thereafter during the study).
• History of or a concomitant medical condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study or compromise the participant's ability to safely complete the study.
• Have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1 (Screening), or within approximately 5 half-lives of the previous investigational compound, whichever is longer.
• For subjects new to Study YKP3089C040 previous exposure to cenobamate or sensitivity/allergy to components of the oral suspension.

Más betegség

• Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 2 years before Visit 1 (Screening).
• 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.
• Presence of only nonmotor simple partial seizures or primary generalized epilepsies.
• 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.
• Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
• 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.
• History of AED-associated rash that involved conjunctiva or mucosae.
• History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication.

Laborértékek

• 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).
• 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).
• Subjects with Familial short QT syndrome.
• 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.
• Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Egyéb

• Females who are breastfeeding or pregnant at Screening or Baseline.

• 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)
• 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)
• Have a minimum weight of 10.0 kilograms (kg) (22.0 pounds [lb])
• Have had a brain imaging (e.g., magnetic resonance imaging [MRI] scan or computed tomography (CT) within 10 years before Visit 1 (Screening) that ruled out a progressive cause of epilepsy.
• 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
• 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).
• Investigator believes subject could benefit from new or continued exposure to study drug
• Subjects entering from study YKP3089C039 must continue to meet all of the inclusion criteria from the YKP3089C039 study
• Subjects receiving felbamate as a concomitant AED must meet the following criteria:
  • 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).
  • No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.
• 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