A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 232
- 试验地点
- 141
- 主要终点
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety and tolerability of the 3 selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3 anti-epileptic drugs (AEDs) compared with placebo for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry
- •Subject has failed to achieve seizure control with >=4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. 'Prior AED' is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)
- •Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month
- •Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments
排除标准
- •Subject has a history of or signs of generalized or combined generalized and focal epilepsy
- •Cluster seizures which are uncountable in the previous 8 weeks before study entry and during 4 weeks prospective baseline
- •Current treatment with carbamazepine, phenytoin, primidone, phenobarbital
- •Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
- •Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
- •Subject has been taking vigabatrin less than 2 years at study entry
- •Subject has been taking felbamate for less than 12 months
- •Subject taking retigabine for less than 4 years
- •Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem, zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies
- •Subject has a current medical condition that occurred within the last 12 months which, in the opinion of the investigator, could compromise his/her safety or ability to participate in this study
研究组 & 干预措施
Padsevonil dosing regimen 1
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Padsevonil (Drug)
Padsevonil dosing regimen 1
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Placebo (Drug)
Padsevonil dosing regimen 2
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Padsevonil (Drug)
Padsevonil dosing regimen 2
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Placebo (Drug)
Padsevonil dosing regimen 3
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Padsevonil (Drug)
Padsevonil dosing regimen 3
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
干预措施: Placebo (Drug)
Placebo
Subjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From Baseline until Safety Follow-Up (up to Week 23)
An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: From Baseline until Safety Follow-Up (up to Week 23)
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is as infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.
Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
时间窗: From Baseline over the 12 Week Maintenance Period (up to Week 16)
During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed seizure frequency from Baseline, with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (Yes or No) and Region (Europe, non-Europe) as categorical factors.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
时间窗: From Baseline until Safety Follow-Up (up to Week 23)
An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.
次要结局
- 75% Responder Rate From Baseline Over the 12-week Maintenance Period(From Baseline over the 12 Week Maintenance Period (up to Week 16))
- 50% Responder Rate From Baseline Over the 12-week Maintenance Period(From Baseline over the 12 Week Maintenance Period (up to Week 16))
- Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period(From Baseline over the 12 Week Maintenance Period (up to Week 16))