Long-term Safety Evaluation of Cenobamate as Adjunctive Therapy in Patients with Primary Generalized Tonic-Clonic Seizures: A Multicenter Open-label Extension Study

The primary objective of this multicenter open-label extension study is to evaluate the **safety** and tolerability of **cenobamate** as an adjunctive therapy in subjects with **Primary Generalized Tonic-Clonic Seizures** (PGTC). This is clinically relevant as it aims to assess the long-term safety profile of cenobamate, which is crucial for determining its viability as a treatment option for patients with PGTC seizures. No secondary objectives are specified for this study.

The clinical trial involves a total of **54 participants** diagnosed with **Primary Generalized Tonic-Clonic Seizures**. The study population includes both male and female subjects, encompassing a broad age range from children to adults. Participants were selected based on their successful completion of a prior double-blind treatment period in a core study, ensuring a specific level of prior treatment experience. The trial includes a vulnerable population, indicating that special considerations are in place to protect these participants. The selection process adhered to stringent criteria, including obtaining informed consent in accordance with International Council for Harmonisation Good Clinical Practice guidelines. The study does not specify particular lifestyle considerations such as diet or physical activity, focusing instead on the medical condition and prior treatment history of the participants.

The clinical trial is designed to evaluate the long-term safety and tolerability of **cenobamate** as an adjunctive therapy in subjects with primary generalized tonic-clonic seizures. This is a multicenter, open-label extension study, which follows a randomized, double-blind, controlled core study. The trial is expected to run until December 2026, with recruitment having commenced in July 2019. Participants who have successfully completed the double-blind treatment period in the core study are eligible for enrollment, provided they meet all inclusion criteria and have given informed consent in accordance with International Council for Harmonisation Good Clinical Practice guidelines.

The trial involves several study visits, beginning with an inclusion (screening) visit to confirm eligibility. Participants will then undergo regular follow-up visits to monitor safety and tolerability, with assessments including adverse events, serious adverse events, clinical laboratory tests, vital signs, physical and neurologic examinations, and electrocardiograms. The primary endpoints focus on safety measures, while secondary endpoints are not specified. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 55 weeks, depending on individual circumstances and adherence to the study protocol.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial employs a placebo control, with participants receiving either **cenobamate** in various formulations or a matching placebo. The maximum daily dose of **cenobamate** is 200 mg, with a total dose not exceeding 77,000 mg over the treatment period. The study aims to provide comprehensive data on the safety profile of **cenobamate** in the specified patient population.

The clinical trial involves the administration of **Cenobamate**, a chemical compound, in various pharmaceutical forms and dosages. The experimental medications include **Cenobamate** in the form of film-coated tablets and oral suspension. The film-coated tablets are available in dosages of 12.5 mg, 25 mg, 50 mg, and 100 mg. The oral suspension is provided at a concentration of 10 mg/mL. All forms of **Cenobamate** are administered orally. The maximum daily dose for the film-coated tablets is 200 mg, while the oral suspension has a maximum daily dose of 3 mg/kg. The treatment period for all forms is capped at 55 days. The sponsor product code for **Cenobamate** is YKP3089, and the product is manufactured by SK LIFE SCIENCE, INC.

In addition to the experimental medication, a placebo is used in the study. The placebo is designed to match the **Cenobamate** tablets and oral suspension in appearance and unit strength, including 12.5 mg, 25 mg, 50 mg, and 100 mg tablets, as well as a 10 mg/kg oral suspension. The placebo does not contain any active substance and serves as a comparator to evaluate the efficacy and safety of **Cenobamate**. The placebo is administered in the same manner as the active medication, ensuring blinding in the study design.

Participant compliance with the dosing schedule is monitored throughout the trial. The trial aims to evaluate the long-term safety and tolerability of **Cenobamate** as an adjunctive therapy in subjects with primary generalized tonic-clonic seizures. The study is conducted under strict regulatory guidelines to ensure the integrity and reliability of the data collected.

The efficacy of **cenobamate** in the clinical trial will be assessed primarily through safety measures, as the main objective is to evaluate the safety and tolerability of **cenobamate** in subjects with primary generalized tonic-clonic seizures. The primary endpoints include the incidences of adverse events (AEs) and serious adverse events (SAEs). Additionally, summary statistics for clinical laboratory test results and vital signs will be collected, along with findings from physical examinations, neurologic examinations, and electrocardiograms (ECGs). These parameters will be measured and collected throughout the trial to ensure comprehensive safety monitoring.