renaissance 2: spn-817 phase 2, double-blind, placebo-controlled study in adults with focal onset seizures

Conditions: Focal Onset Seizures

Summary: this is a phase 2 double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy, safety, and tolerability of spn-817 in adults with focal onset seizures.

this is a phase 2 double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy, safety, and tolerability of spn-817 administered as an adjunctive treatment in adults with focal onset seizures that have previously failed at least 2 anti-seizure medication (asm) regimens. participants will be taking 1 to 4 asms, with at least 4 seizures during the 6-week screening period. following the screening period, eligible participants will be randomized 2:1 to spn-817 (3.0-4.0 mg bid) or placebo and begin the titration period (8-10 weeks). in both treatment groups, open-label ondansetron (8 mg oral \[po\]) will be taken prophylactically approximately 30 minutes before each sm dose (ie, bid) during the first 5 weeks of dose titration as an antiemetic; after the first 5 weeks, ondansetron may be taken as needed as either a preventative or therapeutic antiemetic. after the target dose of 3.0-4.0 mg bid is reached, participants will enter the maintenance period (14 weeks). participants who complete the maintenance period will have the opportunity to enroll in a separate open-label study for continued treatment with spn-817. participants who do not enroll in the open-label study will undergo a tapering period (up to 4 weeks) and a follow-up safety phone call.

Eligibility criteria:
inclusion criteria: 1. diagnosis of treatment-resistant focal epilepsy as adjudicated by the epilepsy study consortium, inc (esci); 2. failed to achieve sustained seizure freedom after ≥2 tolerated, appropriately chosen, and adequately dosed asm drug schedules; 3. able to keep accurate seizure ediaries (with the aid of a caregiver as needed); 4. has a body mass index (bmi) between 18.0 and 40.0 kg/m2; 5. 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; 6. 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 ediary data collection) and no more than a consecutive 21-day period that was seizure free. to be eligible for the study, participants must comply with the ediary on at least 90% of the days of baseline data collection; exclusion criteria: 1. has taken huperzine a within the past 6 months; 2. 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; 3. history of or current nonepileptic events that could be confused by the participant and/or study staff as epileptic seizures; 4. only has seizures that are difficult to count; for example, seizures that are not clinically observable; 5. history of uncountable seizures, such as seizures that happen in a cluster that are too rapid to be counted individually; 6. history of status epilepticus within 6 months prior to screening; 7. 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; 8. 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; 9. chronic concomitant therapy with non-asms that are cholinergic or anticholinergic. 10. history of \>2 allergic reactions to an asm or 1 serious hypersensitivity reaction to an asm; 11. any other reason which, in the opinion of the investigator, would prevent the participant from taking part in the study.

Keywords: focal seizures focal epilepsy phase 2 anti-seizure medication