RENAISSANCE 2: A 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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 216
- 试验地点
- 2
- 主要终点
- Percent change (PCH) from baseline in focal onset seizure frequency per 28 days over the Maintenance Period
研究概览
简要总结
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.
详细描述
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 (or another concomitant medication to assess pharmacological approaches to managing cholinergic adverse events [AEs]) will be taken (8 mg oral [PO]) prophylactically approximately 30 minutes before each study medication (SM) dose (ie, BID) during the Titration Period as an antiemetic. After the target dose of 3.0-4.0 mg BID is reached, participants will enter the Maintenance Period (14 weeks). Ondansetron (or another concomitant medication to assess pharmacological approaches to managing cholinergic AEs) may be taken as needed as either a preventative or therapeutic antiemetic during the Maintenance Period. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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;
排除标准
- •Has taken huperzine A within the past 6 months;
- •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 or current nonepileptic events that could be confused by the participant and/or study staff as epileptic seizures;
- •Only has seizures that are difficult to count; for example, seizures that are not clinically observable;
- •History of uncountable seizures, such as seizures that happen in a cluster that are too rapid to be counted individually;
- •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;
- •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;
- •Chronic concomitant therapy with non-ASMs that have potent cholinergic (central or peripheral) or potent central (only) anticholinergic pharmacology.
- •History of >2 allergic reactions to an ASM or 1 serious hypersensitivity reaction to an ASM;
- •Any other reason which, in the opinion of the Investigator, would prevent the participant from taking part in the study.
研究组 & 干预措施
Placebo
Placebo, bid
干预措施: Placebo (Drug)
SPN-817
SPN-817, bid
干预措施: SPN-817 (Drug)
结局指标
主要结局
Percent change (PCH) from baseline in focal onset seizure frequency per 28 days over the Maintenance Period
时间窗: Baseline and Maintenance Period (Maintenance Week 1-14)
Percent change in 28-day frequency of focal seizures during the 14 week Maintenance Period relative to baseline
次要结局
- Proportion of subjects experiencing ≥50% reduction in focal seizure frequency per 28 days from baseline(Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14)
- PCH from baseline in focal onset seizure frequency per 28 days over the entire Treatment Period(Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14)
- Longest seizure-free interval over the entire Treatment Period(Baseline through Titration Week 1 up to Week 10 and Maintenance Weeks 1-14)
- Incidence of adverse events (AEs)(Baseline through Titration Week 1 up to Week 10, Maintenance Weeks 1-14, and Tapering Period up to Week 4)