Clinical trial NCT05067634: Safety and Efficacy Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures
Official title: Open-Label Safety and Efficacy Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Partial Epilepsy
Keywords: Partial-onset (focal) seizures
Pediatrics
Lead sponsor: SK Life Science, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 140
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Primary objective: To evaluate the safety and tolerability of cenobamate in pediatric subjects 2-17 years of age with partial-onset (focal) seizures

Detailed description: Secondary objectives:

* To evaluate the efficacy of cenobamate tablets and suspension in pediatric subjects with partial onset (focal) seizures
* To evaluate the pharmacokinetics of cenobamate tablets and suspension in pediatric subjects with partial onset seizures
* To evaluate the PK/pharmacodynamics of cenobamate in pediatric subjects with partial onset (focal) seizures
* Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral formulation and the 12.5 mg tablets - Day 1, and Day 15

Eligibility 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 (Screening) 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:

   1. 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).
   2. 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

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 \[i.e., answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) in participants aged 6 and above, if able\].
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 (Screening) or changes in parameter less than 4 weeks before Visit 1 (or thereafter during the study).
21. 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.
22. 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.
23. Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
24. For subjects new to Study YKP3089C040 previous exposure to cenobamate or sensitivity/allergy to components of the oral suspension.

Primary outcomes:
measure: Incidence of Adverse Events and SAEs
timeFrame: 3 Years
Secondary outcomes:
measure: To collect plasma samples of cenobamate to support the evaluation of the pharmacokinetics of cenobamate tablets and suspension in pediatric subjects with partial onset (focal) seizures
timeFrame: 3 Years
measure: Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral formulation and tablets
timeFrame: 3 Years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: Sacramento
country: United States
facility: University of California Davis Health
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Sandy Springs
country: United States
facility: Clinical Integrative Research Center of Atlanta
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research - Savannah Neurology Specialists
state: Georgia
city: Lexington
country: United States
facility: Kentucky Clinic
state: Kentucky
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals Helen DeVos Children's Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri Health Care - Women's and Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Morristown
country: United States
facility: Northeast Regional Epilepsy Group - Morristown
state: New Jersey
city: Hawthorne
country: United States
facility: Boston Children's Health Physicians - Neurology at Hawthorne
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital NeuroDevelopmental Science Center/Pediatric Neurology
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: Dallas
country: United States
facility: Scottish Rite for Children
state: Texas
city: Tacoma
country: United States
facility: MultiCare Institute - Mary Bridge Children's Neurology
state: Washington
city: Heidelberg
country: Australia
facility: Austin Health
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne
city: Randwick
country: Australia
facility: Sydney Children's Hospital - Randwick
city: South Brisbane
country: Australia
facility: Children's Health Queensland Hospital and Health Service
city: Berlin
country: Germany
facility: Charite University Hospital
city: Kehl
country: Germany
facility: Diakonie Kork
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Kiel
city: Munich
country: Germany
facility: Neurologische Klinik und Poliklinik Interdisziplinäres Epilepsiezentrum München
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Budapest
country: Hungary
facility: Bethesda Gyermekkorhaz
city: Budapest
country: Hungary
facility: Országos Klinikai Idegtudományi Intézet, Neurológiai Osztály
city: Budapest
country: Hungary
facility: Semmelweis University Dept. Of Paediatrics
city: Budapest
country: Hungary
facility: Servus Salvus Egészségügyi Szolgáltató Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
city: Cheonju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Kielce
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej - Centrum Neurologii Dzieciecej i Leczenia Padaczki
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Kraków
country: Poland
facility: Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Santiago De Compostela
country: Spain
facility: Instituto de Investigación Sanitaria de la Fundación Ramón Domínguez
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: SK Life Science, Inc.
name: Marc Kamin, MD
role: STUDY_DIRECTOR
References: