RENAISSANCE 2: SPN-817 Phase 2, Double-Blind, Placebo-Controlled Study in Adults With Focal Onset Seizures

Prior treatment

• Prior diagnosis of combined focal and generalized epilepsy syndrome as evidenced by severe developmental delay and multiple seizure types and confirmed by electroencephalography (EEG) (eg, Lennox-Gastaut syndrome). Participants should also be excluded in case of nondiagnostic information;
• History of status epilepticus within 6 months prior to screening;
• Vagus nerve stimulation, deep brain stimulation, responsive neurostimulator system, or other neurostimulation for epilepsy device implanted or activated within 1 year prior to screening; or epilepsy surgery within 1 year prior to screening. Stimulation parameters for devices must have been stable for at least 3 months prior to Screening. Battery change for any epilepsy devices will be allowed; however, stimulation parameters must remain stable during the duration of the study;
• Chronic concomitant therapy with non-ASMs that have potent cholinergic (central or peripheral) or potent central (only) anticholinergic pharmacology.

Other illness

• History of or current nonepileptic events that could be confused by the participant and/or study staff as epileptic seizures;
• History of uncountable seizures, such as seizures that happen in a cluster that are too rapid to be counted individually;
• History of \>2 allergic reactions to an ASM or 1 serious hypersensitivity reaction to an ASM;

Lab values

• Only has seizures that are difficult to count; for example, seizures that are not clinically observable;

Other

• Has taken huperzine A within the past 6 months;
• Any suicidal behavior or suicidal ideation related to item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS assessment in the 1 year before screening; a suicide attempt in the last 2 years before screening; or more than 1 lifetime suicide attempt;
• Any other reason which, in the opinion of the Investigator, would prevent the participant from taking part in the study.

• Diagnosis of treatment-resistant focal epilepsy as adjudicated by the Epilepsy Study Consortium, Inc (ESCI);
• Failed to achieve sustained seizure freedom after ≥2 tolerated, appropriately chosen, and adequately dosed ASM drug schedules;
• Able to keep accurate Seizure electronic diaries \[eDiaries\] (with the aid of a caregiver as needed);
• Has a body mass index (BMI) between 18.0 and 40.0 kg/m2;
• Treatment with a stable dose of 1 to 4 current ASMs for ≥28 days prior to screening. If following a diet plan along with the ASM, the participant should have been on a stable diet plan for at least 1 month prior to Visit 1. The diet plan should be maintained throughout the duration of the study;
• At least 4 clinically observable focal onset seizures accepted by the ESCI prior to the first dose of SM (during the days of baseline Seizure electronic diary \[eDiary\] data collection) and no more than a consecutive 21-day period that was free of these seizures. To be eligible for the study, participants must comply with the eDiary on at least 80% of the days of baseline data collection;