Safety and Efficacy Extension Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
Secondary objectives:
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To evaluate the efficacy of cenobamate tablets and suspension in pediatric subjects with partial onset (focal) seizures
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To evaluate the pharmacokinetics of cenobamate tablets and suspension in pediatric subjects with partial onset seizures
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To evaluate the PK/pharmacodynamics of cenobamate in pediatric subjects with partial onset (focal) seizures
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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 Design
Arms and Interventions
| 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.
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| 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.
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| 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.
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| Experimental: 2 to <4 years old
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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.
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Outcome Measures
Primary Outcome Measures
- Incidence of Adverse Events and SAEs [3 Years]
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
Secondary Outcome Measures
- 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 [3 Years]
The area under the curve (AUC) of Xcopri after a single and multiple doses of Xcopri
- Acceptability and palatability assessment (determined by a 5-point Hedonic Scale) of the oral formulation and tablets [3 Years]
Testing to determine how patients respond to the taste and route of Xcopri
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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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)
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Have a minimum weight of 12.5 kilograms (kg) (27.5 pounds [lb])
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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
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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
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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.
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Investigator believes subject could benefit from new or continued exposure to study drug
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Subjects must continue to meet all of the inclusion criteria from the YKP3089C039 study
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Subjects receiving felbamate as a concomitant AED must meet the following criteria:
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Have an 18-month history of felbamate use and a history of a fixed dosing regimenfor a minimum of 60 days prior to Visit 1 (Screening/Baseline).
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No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.
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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:
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Females who are breastfeeding or pregnant at Screening or Baseline
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Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 2 years before Visit 1.
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Have a history of status epilepticus that required hospitalization during the 6 months before Visit 1.
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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).
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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.
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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.
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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.
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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.
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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).
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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).
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Subjects with Familial short QT syndrome
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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 ms.
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Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
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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.
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History of AED-associated rash that involved conjunctiva or mucosae.
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History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication.
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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.
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A history of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hourperiod is considered a 1- time rescue) more than once within the 30 days prior to Visit1 (Screening/Baseline).
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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)
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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.
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Have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer.
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Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix Children's Hospital | Phoenix | Arizona | United States | 85016 |
| 2 | Mid-Atlantic Epilepsy and Sleep Center | Bethesda | Maryland | United States | 20817 |
| 3 | Le Bonheur Children's Hospital | Memphis | Tennessee | United States | 38103 |
Sponsors and Collaborators
- SK Life Science, Inc.
Investigators
- Study Director: Marc Kamin, MD, SK Life Science, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- YKP3089C040