Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study - Determine Efficacy and Safety of Two Doses of Retigabine (900 Mg/Day and 600 Mg/Day) Used as Adjunctive Therapy in Refractory Epilepsy Patients With Partial-Onset Seizures
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 539
- 试验地点
- 70
- 主要终点
- Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
研究概览
简要总结
This Phase 3 study is being conducted to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs).
详细描述
This Phase 3 study is being conducted in Europe, Israel, Australia, and South Africa to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs). The primary objective is to demonstrate a superior change in total partial seizure frequency for four weeks from baseline to the double-blind period. The proportion of responders (greater than or equal to 50% reduction in seizure frequency for four weeks from baseline to the double-blind period) will also be evaluated.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of refractory epilepsy with simple or complex partial onset seizures with or without secondary generalization
- •28-day partial seizure frequency rate of four or more partial seizures over the 8-week baseline phase
- •Currently treated with up to three established AEDs
- •Vagal Nerve Stimulator may be included
排除标准
- •Existing medical or psychiatric condition which could affect patient's health or compromise ability to participate in the study
- •Clinically significant abnormalities on physical exam, vital signs, ECG, or liver function tests
- •Impaired renal function (creatinine clearance less than 50 mL/minute)
- •Evidence of progressive central nervous disease, lesion, or encephalopathy
- •History of primary generalized seizures
- •History of clustering or flurries or status epilepticus within 12 months of study entry
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Retigabine 600 mg
干预措施: Retigabine (Drug)
Retigabine 900 mg
干预措施: Retigabine (Drug)
结局指标
主要结局
Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
时间窗: Week 5 through Week 16
Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period.
Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)
时间窗: Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
28-day total PS (PSs \[also called focal seizures\] are seizures limited to a specific area of the brain) frequency in the BL period = (Number \[No.\] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = (\[value in the DB period minus value at BL\] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency.
次要结局
- Number of Participants Who Were Responders and Non-responders During the DB Phase(Week 1 through Week 16)
- Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase(Baseline (Week -7 through Week 0), Week 5 through Week 16)
- Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories(Baseline (Week -7 through Week 0), Week 1 through Week 16)
- Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories(Baseline (Week -7 through Week 0), Week 1 through Week 16)
- Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase(Baseline (Week -7 through Week 0), Week 5 through Week 16)
- Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase(Baseline (Week -7 through Week 0), Week 5 through Week 16)
- Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline(Baseline (Week -7 through Week 0), Week 1 through Week 16)
- Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)(Week 1 through Week 16)
- Patient Global Impression (PGI) Score at the End of the Maintenance Phase(Week 16/end of treatment phase)
- Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase(Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase)
- Number of Participants Who Were Seizure-free During the Maintenance Phase(Week 5 through Week 16)
- Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)(Week 1 through Week 16)
- Percentage of Seizure-free Days During the Maintenance Phase(Week 5 through Week 16)
- Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase(Week 16/end of treatment phase)
- Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)(Week 1 through Week 16)
- Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16(End of Baseline (Week 0), Weeks 4, 8, and 16)
- Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)(Week 1 through Week 16)
- Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase(Baseline (Week -7 through 0), Weeks 8 and 16)