Cenobamate for Treatment of Pediatric Patients with Focal Epilepsy: Design of a Phase I Study with Open-Label Extension
Abstract number :
1.28
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2023
Submission ID :
168
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Vijaykumar Vashi, PhD – SK Life Science, Inc.
Louis Ferrari, RPh, MBA – SK Life Science, Inc.; William Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults
Rationale:
Cenobamate is an antiseizure medication (ASM) approved in the United States (XCOPRI®) and Europe (ONTOZRY®) for the treatment of focal seizures in adult patients. Individual retrospective studies indicate potential efficacy in pediatric epilepsy. Two clinical studies (Study C039 [NCT04903314] and Study C040 [NCT05067634]) assessing the pharmacokinetics (PK), safety, and tolerability of cenobamate in pediatric patients with focal seizures following single and multiple dosing are currently underway. Study C040 will also examine efficacy outcomes.
Methods:
Study C039 is a phase I, open-label, dose-escalation study being conducted at six sites in the United States to determine the cenobamate dosing regimen in pediatric patients. Eligible patients (n=24) are male or female, aged two to seventeen years, with established diagnosis of epilepsy with focal seizures at the time of parent/caregiver informed consent. The study includes four age-based cohorts: Cohort I, Cohort IIa, Cohort IIb, and Cohort III (Table 1). Patients undergo cenobamate titration (tablets for Cohort I or oral suspension for other cohorts) every two weeks to a maintenance dose not to exceed 400 mg/day or pediatric equivalent dose, with a treatment period of at least 144 days. Dose escalation is based on safety, tolerability, and plasma cenobamate exposure parameters. Enrollment in the cohorts is sequential starting with Cohort I. Based on the PK results of the completed Cohort I patients and utilizing population PK modeling and simulations, a weight-based dosing regimen for Cohorts IIa and IIb was determined (Table 2). Appropriate dosing for Cohort III will be determined using a population PK modeling approach that includes adult data and data from Cohorts I and IIa and IIb (Table 1). Patients attaining maintenance dose and completing Study C039 will be offered enrollment into Study C040, a phase 3 open-label study with anticipated enrollment of 140 patients (n=24 from C039; n=116 direct entry) that will evaluate the safety, tolerability, and efficacy of cenobamate.
Results:
Currently, sequential enrollment has reached Cohorts IIa and IIb.
Conclusions:
Studies C039 and C040 will provide PK, safety, tolerability, and efficacy information for cenobamate tablets and oral suspension in pediatric patients with focal seizures. Recruitment in both studies is ongoing.
Funding:
Funded by SK Life Science, Inc.
Anti-seizure Medications