Evaluation of BHV-7000 as Adjunctive Therapy in Idiopathic Generalized Epilepsy with Generalized Tonic-clonic Seizures: A Randomized, Double-blind, Placebo-controlled Study

The primary objective of this study is to compare the **efficacy** of BHV-7000 to placebo as adjunctive therapy in subjects with **Idiopathic Generalized Epilepsy** with **Generalized Tonic-clonic Seizures** (GTC). This will be measured by the time to the second day with a GTC seizure during the double-blind phase. This objective is clinically relevant as it aims to determine the potential of BHV-7000 to reduce the frequency of GTC seizures, which are a significant concern in patients with this type of epilepsy.

Secondary objectives include:

• Comparing the efficacy of BHV-7000 to that of placebo in terms of the proportion of subjects that are free of GTC seizures.
• Assessing the safety and tolerability of BHV-7000.

These secondary objectives are crucial for understanding the broader impact of BHV-7000 on patient outcomes, including its potential to improve seizure control and its safety profile in the target population.

The clinical trial involves a total of **124 participants** diagnosed with **Idiopathic Generalized Epilepsy** (IGE) with Generalized Tonic-clonic Seizures (GTC). The study population includes both male and female subjects aged between 18 to 75 years. Participants were selected based on their diagnosis of IGE at least six months prior to the screening visit, as defined by the 2017 International League Against Epilepsy (ILAE) Classification. The trial includes individuals with probable or possible GTC seizures in the setting of IGE, characterized by specific electroencephalogram (EEG) patterns. Participants are required to have a history of drug-resistant epilepsy, having failed adequate trials of two anti-seizure medication schedules. The ability to maintain accurate seizure diaries is essential. Current treatment regimens include at least one to three anti-seizure medications, with a maximum of four epilepsy treatments in total. Participants must have experienced at least three days with a GTC seizure evenly spread over the 16 weeks prior to the screening visit. The trial population is considered vulnerable, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and tolerability of **BHV-7000** as an adjunctive therapy in subjects with **Idiopathic Generalized Epilepsy** with generalized tonic-clonic seizures. The trial will include an open-label extension phase. The primary objective is to compare the efficacy of BHV-7000 to placebo by measuring the time to the second day with a generalized tonic-clonic seizure during the double-blind phase. The trial is expected to commence recruitment on September 1, 2024, and conclude by November 30, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and seizure history. The trial will include follow-up visits to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will assess the overall outcomes and gather final data. The expected duration of participant involvement is up to 72 weeks, with conditions for early termination including significant adverse events or withdrawal of consent.

Participants will be randomly assigned to receive either BHV-7000 or a placebo, both administered as **prolonged-release tablets** via the oral route. The maximum daily dose of BHV-7000 is 75 mg, with a total maximum dose of 37,800 mg over the treatment period. The study will assess primary endpoints such as the time to the second day with a generalized tonic-clonic seizure and secondary endpoints including the proportion of subjects achieving seizure freedom and safety assessments. Safety will be evaluated by monitoring adverse events, laboratory abnormalities, and other clinical parameters throughout the trial.

The clinical trial involves the administration of **BHV-7000**, an experimental medication developed by Biohaven Therapeutics Ltd. BHV-7000 is formulated as a **prolonged-release tablet** and is intended for oral administration. The active substance, also named BHV-7000, is of chemical origin and is synonymous with BPN-25203 and KB-3061. The maximum daily dose of BHV-7000 is 75 mg, with a total maximum dose of 37,800 mg over a treatment period of up to 72 days. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the efficacy, safety, and tolerability of BHV-7000 as an adjunctive therapy in subjects with idiopathic generalized epilepsy with generalized tonic-clonic seizures.

The study also includes a **placebo** group to serve as a comparator for the experimental treatment. The placebo is designed to match the BHV-7000 in appearance but does not contain any active pharmaceutical ingredients. The placebo is administered in the same manner as the BHV-7000, ensuring that the study remains double-blind. This allows for an unbiased comparison of the effects of the experimental medication against the placebo, providing a robust assessment of BHV-7000's therapeutic potential.

The efficacy of the investigational product **BHV-7000** in the clinical trial will be assessed primarily by measuring the time to the second day with a generalized tonic-clonic (GTC) seizure during the double-blind phase. This primary endpoint is designed to evaluate the effectiveness of **BHV-7000** as an adjunctive therapy in subjects with Idiopathic Generalized Epilepsy (IGE) experiencing GTC seizures. Secondary endpoints include the proportion of subjects achieving GTC seizure freedom during the 24-week double-blind phase, which will be estimated using Kaplan-Meier methods. Additionally, safety assessments will be conducted by monitoring the number of unique subjects experiencing deaths, serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, moderate and severe AEs, and grade 3 and grade 4 laboratory abnormalities.