CENOBAMATE for Partial-onset (focal) seizures

Inclusion criteria

• {"criterion_text":"- 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. For participants aged 6 to less than 18 years a diagnosis should have been established at least 12 months prior to Visit 1 (Screening). For participants aged 2 to less than 6 years, a diagnosisshould have been established at least 1 month prior to Visit 1 (Screening). Diagnosis should be supported 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Have a minimum weight of 10.0 kilograms (kg) (27.0 pounds [lb])"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Investigator believes subject could benefit from new or continued exposure to study drug"}
• {"criterion_text":"- Subjects entering from study YKP3089C039 must continue to meet all of the inclusion criteria from the YKP3089C039 study"}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- Females who are breastfeeding or pregnant at Screening or Baseline"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Subjects with Familial short QT syndrome"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History of AED-associated rash that involved conjunctiva or mucosae."}
• {"criterion_text":"- History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 2 years before Visit 1 (Screening)."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption."}
• {"criterion_text":"- For subjects new to Study YKP3089C040 previous exposure to cenobamate or sensitivity/allergy to components of the oral suspension. Any potential exception to exclusion criteria allowing de minimis (clinically trivial and meaningless) variations must be approved by the medical monitor."}
• {"criterion_text":"- Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1 (Screening)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Presence of only nonmotor simple partial seizures or primary generalized epilepsies."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Number of participants with any treatment-emergent adverse event (TEAE) and any serious adverse event (SAE) during the first year of exposure","definition_or_measurement_approach":"Count of participants experiencing any TEAE and any SAE recorded during the first year of exposure to cenobamate (safety monitoring over first year)."}

Secondary endpoints

• {"endpoint_text":"- Percent change in seizure frequency over 28 days during the Treatment Period and during each phase of the study","definition_or_measurement_approach":"Percent change from baseline in seizure frequency measured over 28-day intervals during treatment and study phases."}
• {"endpoint_text":"- Number of participants who are seizure-free during the Treatment Period and during each phase of the study","definition_or_measurement_approach":"Count of participants recorded as seizure-free during treatment and during each study phase."}
• {"endpoint_text":"- Percentage of responders (50%, 75%, and 90% responders) during the Treatment Period and during each phase of the study","definition_or_measurement_approach":"Proportion of participants achieving ≥50%, ≥75%, and ≥90% reduction in seizure frequency during treatment and study phases."}
• {"endpoint_text":"- Change from Baseline in A-B neuropsychological assessment schedule (ABNAS) end of titration, end of maintenance and 52 weeks","definition_or_measurement_approach":"Change from baseline in ABNAS score measured at end of titration, end of maintenance, and at 52 weeks."}
• {"endpoint_text":"- Change from Baseline in Child Behavior Checklist (CBCL) scores end of titration, end ofmaintenance and 52 weeks","definition_or_measurement_approach":"Change from baseline in CBCL scores assessed at specified timepoints (end of titration, end of maintenance, 52 weeks)."}
• {"endpoint_text":"- Change from Baseline in Lafayette Grooved Pegboard Test (LGPT) scores end of titration, end of maintenance and 52 weeks","definition_or_measurement_approach":"Change from baseline in LGPT performance at end of titration, end of maintenance, and 52 weeks."}
• {"endpoint_text":"- Change from Baseline in height","definition_or_measurement_approach":"Change in participant height from baseline measured at protocol-specified visits."}
• {"endpoint_text":"- Change from Baseline in weight","definition_or_measurement_approach":"Change in participant weight from baseline measured at protocol-specified visits."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion of participants with treatment-emergent suicidal ideation/behavior as measured by C-SSRS (age-appropriate versions) during treatment."}
• {"endpoint_text":"- Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral suspension and tablets Visit 2 and Visit 3.","definition_or_measurement_approach":"Acceptability/palatability measured using a 5-point Hedonic Scale for oral suspension and tablets at Visit 2 and Visit 3."}

Germany

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

24-04-2025

Processing Time Days

380

Number Of Sites

2

Number Of Participants

15

Hungary

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

28-04-2025

Processing Time Days

384

Number Of Sites

5

Number Of Participants

26

Poland

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

27-04-2025

Processing Time Days

383

Number Of Sites

3

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

22-04-2025

Processing Time Days

378

Number Of Sites

5

Number Of Participants

19

Primary sponsor

Full Name

Sk Life Science Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Preparation of applications to CA and Ethics committee; other listed sponsor duties (codes 1,12,15,5)

Name

Iqvia Rds Ireland Limited

Responsibilities

Pharmacovigilance

Name

Medidata Solutions Inc.

Responsibilities

eClinical platform / data services (sponsor duties code: 7; specific responsibility description provided as contact)

Name

Almac Clinical Technologies LLC

Responsibilities

IVRS – treatment randomisation

Name

MEDPACE LABORATORIES

Responsibilities

Central laboratory services

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code: 7 (role details not specified in record)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement and transportation","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Njs Associates Company","duties_or_roles":"Sponsor duties code: 10 (role details not specified in record)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"IP QP Release site (sponsor duties codes include 14 and 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Iqvia Rds Ireland Limited","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"PK labs","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"Central laboratory services","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Preparation of applications to CA and Ethics committee; other sponsor duties (codes 1,12,15,5)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}