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

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

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

Study Overview

• Status: Recruiting
• Conditions: Partial Epilepsy
• Intervention / Treatment: Drug: Xcopri

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

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Meagan Whritner; Phone Number: 201-431-7812; Email: mwhritner@sklsi.com
• Study Contact Backup: Name: Sunita Misra, MD, PhD; Email: smisra@sklsi.com

Study Locations

• Australia
  • Heidelberg, Australia
    • Recruiting
    • Austin Health
    • Principal Investigator: Ingrid Scheffer, MD
  • Parkville, Australia
    • Recruiting
    • Royal Children's Hospital Melbourne
    • Principal Investigator: Jeremy Freeman, MD
  • Randwick, Australia
    • Recruiting
    • Sydney Children's Hospital - Randwick
    • Principal Investigator: Denise Chan, MD
  • South Brisbane, Australia
    • Recruiting
    • Children's Health Queensland Hospital and Health Service
    • Principal Investigator: Catherine Riney, MD
• Germany
  • Berlin, Germany
    • Recruiting
    • Charité University Hospital
    • Principal Investigator: Angela Kaindl, MD
  • Kehl, Germany
    • Recruiting
    • Diakonie Kork
    • Contact: Phone Number: 497851842231
    • Principal Investigator: Thomas Bast, MD
  • Kiel, Germany
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein - Campus Kiel
    • Contact: Phone Number: +49 431 5000
    • Principal Investigator: Hiltrud Muhle, MD
  • Munich, Germany
    • Recruiting
    • Neurologische Klinik und Poliklinik Interdisziplinäres Epilepsiezentrum München
    • Contact: Phone Number: +49 89 440072685
    • Principal Investigator: Ingo Borggräfe, MD
  • Tübingen, Germany
    • Recruiting
    • Universitätsklinik für Kinder- und Jugendmedizin Tübingen
    • Contact: Phone Number: +49 7071 29 81391
    • Principal Investigator: Michael Alber, MD
• Hungary
  • Budapest, Hungary
    • Recruiting
    • Bethesda Gyermekkórház
    • Contact: Phone Number: 36301806632
    • Principal Investigator: Andras Fogarasi, MD
  • Budapest, Hungary
    • Recruiting
    • Semmelweis University Dept. Of Paediatrics
    • Contact: Phone Number: 36304330361
    • Principal Investigator: Viktor Farkas, MD
  • Budapest, Hungary
    • Recruiting
    • Országos Klinikai Idegtudományi Intézet, Neurológiai Osztály
    • Contact: Phone Number: 36306894248
    • Principal Investigator: Anna Kelemen, MD
  • Budapest, Hungary
    • Recruiting
    • Servus Salvus Egészségügyi Szolgáltató Kft.
    • Principal Investigator: Anna Altmann, MD
  • Debrecen, Hungary
    • Recruiting
    • Debreceni Egyetem Klinikai Kozpont
    • Contact: Phone Number: 36 70 945 0368
    • Principal Investigator: Monika Bessenyei, MD
• Korea, Republic of
  • Cheonju, Korea, Republic of
    • Recruiting
    • Chungbuk National University Hospital
    • Contact: Phone Number: +82-43-269-6537
    • Principal Investigator: Won Seop Kim, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Phone Number: +82 1588-5700
    • Principal Investigator: Ki Joong Kim, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Principal Investigator: Ara Ko, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Phone Number: +82 1577-9966
    • Principal Investigator: Baik Lin Eun, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • SMG-SNU Boramae Medical Center
    • Contact: Phone Number: 02-870-2177
    • Principal Investigator: Ji Eun Choi, MD
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Hospital
    • Contact: Phone Number: +82-31-219-4252
    • Principal Investigator: Da-Eun Jung, MD
• Poland
  • Kielce, Poland
    • Recruiting
    • Niepubliczny Zaklad Opieki Zdrowotnej - Centrum Neurologii Dzieciecej i Leczenia Padaczki
    • Contact: Phone Number: 48604091678
    • Principal Investigator: Anna Gniatkowska-Nowakowska, MD
  • Kraków, Poland
    • Recruiting
    • Wojewodzki Specjalistyczny Szpital Dzieciecy im. Sw. Ludwika w Krakowie
    • Contact: Phone Number: 48601821033
    • Principal Investigator: Barbara Prawzdic-Senkowska, MD
  • Kraków, Poland
    • Recruiting
    • Centrum Medyczne Plejady
    • Principal Investigator: Marta Zolnowska, MD
    • Contact: Phone Number: 48608336668
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Phone Number: +34 934 89 30 00
    • Principal Investigator: Miquel Raspall Chaure, MD
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Joan de Déu Barcelona
    • Contact: Phone Number: +34 936009733
    • Principal Investigator: Javier Aparicio Calvo, MD
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Phone Number: +34 917 27 70 00
    • Principal Investigator: Pilar Tirado, MD
  • Madrid, Spain
    • Recruiting
    • Hospital Infantil Universitario Niño Jesús
    • Contact: Phone Number: +34 915 03 59 00
    • Principal Investigator: Victor Soto Insuga, MD
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra - Pamplona
    • Contact: Phone Number: 34 948 25 54 00
    • Principal Investigator: Rocio Sanchez-Carpintero, MD
  • Santiago De Compostela, Spain
    • Recruiting
    • Instituto de Investigación Sanitaria de la Fundación Ramón Domínguez
    • Contact: Phone Number: 981951121
    • Principal Investigator: Manuel Jesus Eiris-Punal, MD
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Phone Number: 34 955 013 767
    • Principal Investigator: Barbara Blanco Martinez, MD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
      • Principal Investigator: Angus Wilfong, MD
      • Contact: Phone Number: 602-933-0970
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital Stanford
      • Contact: Phone Number: 650-497-8000
      • Principal Investigator: William Gallentine, MD
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis Health
      • Principal Investigator: Temitayo Oyegbile-Chidi, MD
      • Contact: Phone Number: 916-471-4417
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Recruiting
      • Connecticut Children's Medical Center
      • Contact: Phone Number: 860-837-7500
      • Principal Investigator: Jennifer Madan Cohen, MD
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta University Medical Center
      • Contact: Phone Number: 706-721-2196
      • Principal Investigator: Young Park, MD
    • Sandy Springs, Georgia, United States, 30328
      • Recruiting
      • Clinical Integrative Research Center of Atlanta
      • Contact: Phone Number: 678-705-7341
      • Principal Investigator: Julio Robert Flamini, MD
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Meridian Clinical Research - Savannah Neurology Specialists
      • Contact: Phone Number: 912-790-4837
      • Principal Investigator: Katherine Moretz, MD
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Kentucky Clinic
      • Contact: Phone Number: 859-257-8562
      • Principal Investigator: Gulam Khan, MD
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy and Sleep Center
      • Principal Investigator: Pavel Klein, MD
      • Contact: Arkady Barber; Phone Number: 301-530-9744
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Phone Number: 617-726-6540
      • Principal Investigator: Elizabeth Thiele, MD
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Spectrum Health Hospitals Helen DeVos Children's Hospital
      • Contact: Phone Number: 616-267-2500
      • Principal Investigator: Robin Cook, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic - Rochester
      • Contact: Phone Number: 507-284-2511
      • Principal Investigator: Lily Wong-Kisiel, MD
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • University of Missouri Health Care - Pediatric and Adolescent Specialty Clinic
      • Principal Investigator: Paul Carney, MD
      • Contact: Phone Number: 573-882-6921
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Northeast Regional Epilepsy Group
      • Principal Investigator: Eric Segal, MD
      • Contact: Phone Number: 201-343-6676
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Northeast Regional Epilepsy Group - Morristown
      • Principal Investigator: Rajeshwari Mahalingam, MD
  • New York
    • Hawthorne, New York, United States, 10532
      • Recruiting
      • Boston Children's Health Physicians - Neurology at Hawthorne
      • Contact: Phone Number: 914-768-3970
      • Principal Investigator: Steven Wolf, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Phone Number: 919-668-0477
      • Principal Investigator: Muhammad Zafar, MD
  • Ohio
    • Akron, Ohio, United States, 44308
      • Recruiting
      • Akron Children's Hospital NeuroDevelopmental Science Center/Pediatric Neurology
      • Contact: Phone Number: 330-543-4064
      • Principal Investigator: Michael Kohrman, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Main Campus
      • Contact: Phone Number: 216-444-8012
      • Principal Investigator: Deepak Lachhwani, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Phone Number: 215-590-1719
      • Principal Investigator: Sudha Kessler, MD
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Recruiting
      • Le Bonheur Children's Hospital
      • Principal Investigator: James Wheless, MD
      • Contact: Phone Number: 901-287-5207
  • Texas
    • Austin, Texas, United States, 78731
      • Recruiting
      • Child Neurology Consultants of Austin
      • Principal Investigator: Karen Keough, MD
      • Contact: Phone Number: 512-494-4024
    • Dallas, Texas, United States, 75219
      • Recruiting
      • Scottish Rite for Children
      • Contact: Phone Number: 214-559-7828
      • Principal Investigator: Steven Sparagana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12 to < 18 year olds	Drug: Xcopri; Age groups 12 to <18 will enroll once dosing data is received from Cohort I of the PK analysis of YKP3089C039 study. Age groups 6 to <12 will enroll once dosing data is received from Cohort IIa of the PK analysis of YKP3089C039 study. Age groups 4 to <6 will enroll once dosing data is received from Cohort IIb of the PK analysis of YKP3089C039 study. Age groups 2 to <4 will enroll once dosing data is received from Cohort III of the PK analysis of YKP3089C039 study.
Experimental: 6 to <12 years old	Drug: Xcopri; Age groups 12 to <18 will enroll once dosing data is received from Cohort I of the PK analysis of YKP3089C039 study. Age groups 6 to <12 will enroll once dosing data is received from Cohort IIa of the PK analysis of YKP3089C039 study. Age groups 4 to <6 will enroll once dosing data is received from Cohort IIb of the PK analysis of YKP3089C039 study. Age groups 2 to <4 will enroll once dosing data is received from Cohort III of the PK analysis of YKP3089C039 study.
Experimental: 4 to <6 years old	Drug: Xcopri; Age groups 12 to <18 will enroll once dosing data is received from Cohort I of the PK analysis of YKP3089C039 study. Age groups 6 to <12 will enroll once dosing data is received from Cohort IIa of the PK analysis of YKP3089C039 study. Age groups 4 to <6 will enroll once dosing data is received from Cohort IIb of the PK analysis of YKP3089C039 study. Age groups 2 to <4 will enroll once dosing data is received from Cohort III of the PK analysis of YKP3089C039 study.
Experimental: 2 to <4 years old	Drug: Xcopri; Age groups 12 to <18 will enroll once dosing data is received from Cohort I of the PK analysis of YKP3089C039 study. Age groups 6 to <12 will enroll once dosing data is received from Cohort IIa of the PK analysis of YKP3089C039 study. Age groups 4 to <6 will enroll once dosing data is received from Cohort IIb of the PK analysis of YKP3089C039 study. Age groups 2 to <4 will enroll once dosing data is received from Cohort III of the PK analysis of YKP3089C039 study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events and SAEs	Summary statistics for clinical laboratory test results and vital signs; and physical examination, neurologic examination and electrocardiogram (ECG) finding.of age with partial-onset (focal) seizures	3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The area under the curve (AUC) of Xcopri after a single and multiple doses of Xcopri	3 Years
Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral formulation and tablets	Testing to determine how patients respond to the taste and route of Xcopri	3 Years

Collaborators and Investigators

• Sponsor: SK Life Science, Inc.
• Investigators: Study Director: Marc Kamin, MD, SK Life Science, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Pediatrics; Partial-onset (focal) seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Epilepsies, Partial; Anticonvulsants; Cenobamate
• Other Study ID Numbers: YKP3089C040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No