A Multicenter, Double-Blind, Randomized, Cross-Over Study Evaluating Pharmacodynamic Activity of E2730 in Adult Subjects With Photosensitive Epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Eisai Inc.
- 入组人数
- 6
- 试验地点
- 5
- 主要终点
- Mean Change From Baseline in the Standard Photosensitivity Response (SPR) in the Most Sensitive Eye Condition at 8 Hours Post-dose on Day 1 of Each Treatment Period
研究概览
简要总结
The primary purpose of the study is to assess the pharmacodynamic (PD) activity of E2730 as measured by suppression of epileptic photoparoxysmal response (PPR) in the participant's most sensitive eye condition in participants with photosensitive epilepsy.
详细描述
Adult participants with epilepsy will be enrolled in this study. This study will consist of 2 phases: Prerandomization and Randomization Phase.
The Prerandomization Phase will consist of a Screening Period (up to 3 weeks), during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of 3 Treatment Periods with a single dose in each period (placebo, E2730 40 mg, or E2730 120 mg), each separated by a 3-week washout interval for a total of approximately 6 weeks, and a Follow-up Period (3 weeks after the last dose of study drug).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female 18 to 60 years old at the time of informed consent.
- •A diagnosis and history of a PPR on EEG with or without a diagnosis of epilepsy.
- •Currently taking up to a maximum of 3 concomitant antiepileptic drugs (AEDs). If taking concomitant AED(s), the dose must have remained stable for at least 4 weeks prior to Screening.
- •A reproducible intermittent photic stimulation (IPS)-induced PPR on EEG of at least 3 points on a frequency assessment scale (SPR) in at least 1 eye condition on at least 3 of the EEGs performed at Screening.
- •A body mass index (BMI) between 18 to 35 kilogram per square meter (kg/m^2) and a total body weight greater than or equal to 45 kilograms (kg) at the time of Screening.
排除标准
- •Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 international units per liter [IU/L] or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- •History of nonepileptic seizures (eg, metabolic, structural, or pseudoseizures) while on any antiepileptic medication(s).
- •History of status epilepticus while on any antiepileptic medication(s) within 2 years prior to Screening.
- •Ongoing or history of generalized tonic-clonic seizures within 6 months prior to Screening.
- •Previously developed or who experienced a clinical seizure during prior PPR assessment or Screening IPS procedure, respectively.
- •Use of AEDs that affect gama-aminobutyric acid (GABA) (GABAergic AEDs) (such as tiagabine, vigabatrin, gabapentin, pregabalin) within 3 months prior to Screening.
- •Multiple drug allergies or a severe drug reaction to AED(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
- •An active central nervous system (CNS) infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
- •Concomitant use of cannabinoids.
- •Inability to follow restriction on watching television, or use of any device with an animated screen (ie, computer, video games, tablets).
- •A history of prolonged QT syndrome or risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome), or the use of concomitant medications that prolonged the QT/corrected QT (QTc) interval; or prolonged QT/QTc interval (QTc greater than [>] 450 millisecond [msec]) demonstrated on electrocardiograms (ECG) at Screening or baseline (based on average of triplicate ECGs).
- •Any suicidal ideation with intent with or without a plan within 6 months before Screening or during Screening (ie, answering "Yes" to questions 4 or 5 on the suicidal ideation section of the Columbia-Suicide Severity Rating Scale [C-SSRS]).
- •Any lifetime suicidal behavior (per the suicidal behavior section of the C-SSRS).
- •Any psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years.
- •Frequent spontaneous background burst or current evidence of proconvulsive activity on EEG (eg, increase in spike-wave activity) at Screening.
研究组 & 干预措施
Placebo, E2730 40 mg, E2730 120 mg
Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
Placebo, E2730 40 mg, E2730 120 mg
Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
E2730 40 mg, E2730 120 mg, Placebo
Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
E2730 40 mg, E2730 120 mg, Placebo
Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
E2730 120 mg, Placebo, E2730 40 mg
Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
E2730 120 mg, Placebo, E2730 40 mg
Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
Placebo, E2730 120 mg, E2730 40 mg
Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
Placebo, E2730 120 mg, E2730 40 mg
Participants will receive a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 1 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 2 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
E2730 40 mg, Placebo, E2730 120 mg
Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
E2730 40 mg, Placebo, E2730 120 mg
Participants will receive a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 1 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 2 followed by a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
E2730 120 mg, E2730 40 mg, Placebo
Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: Placebo (Drug)
E2730 120 mg, E2730 40 mg, Placebo
Participants will receive a single dose of E2730 120 mg, capsule, orally (Treatment C) in Treatment Period 1 followed by a single dose of E2730 40 mg, capsule, orally (Treatment B) in Treatment Period 2 followed by a single dose of E2730-matched placebo, capsule, orally (Treatment A) in Treatment Period 3. A wash-out phase of at least 3-weeks will be maintained between the treatment periods.
干预措施: E2730 (Drug)
结局指标
主要结局
Mean Change From Baseline in the Standard Photosensitivity Response (SPR) in the Most Sensitive Eye Condition at 8 Hours Post-dose on Day 1 of Each Treatment Period
时间窗: Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period
Photosensitivity described the presentation of an epileptiform electroencephalogram (EEG) response PPR from exposure to intermittent photic stimulation (IPS). SPR was a standardized derived measure of the range of frequencies of IPS that elicits epileptiform EEG responses in a participant. The participants were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The range was then assigned a number, representing the number of frequency steps, ranging from 0 to 14 between the lowest to the highest frequencies of IPS that elicits epileptiform activity by EEG. The lower scores represented better outcomes. Day 1 as per assigned treatment sequence in Treatment Period 1, 2, or 3. Mean change from baseline in the SPR most sensitive eye condition was the average of SPR scores assessed post study drug administration (Day 1 of Treatment Period 1, 2, or 3).
次要结局
- Number of Participants With Clinically Significant Change From Baseline Values for Laboratory Parameters: Clinical Chemistry, Hematology and Liver Function Test(First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71))
- Cmax: Maximum Observed Plasma Concentration for E2730 and N-acetyl Metabolite(Days 1, 22 and 43: 0-8 hours post-dose)
- Tmax: Time to Reach Maximum Plasma Concentration (Cmax) for E2730 and N-acetyl Metabolite(Days 1, 22 and 43: 0-8 hours post-dose)
- AUC (0-8h): Area Under the Plasma Concentration-time Curve From 0 to 8 Hours Post-dose for E2730 and N-acetyl Metabolite(Days 1, 22 and 43: 0-8 hours post-dose)
- Model Based Relationship Between PK Parameters of E2730 and Onset, Maximum Change, and Duration of Impact on Photosensitivity(Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71))
- Mean Change From Baseline in SPR in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Opened) at 8 Hours Post-dose on Day 1 of Each Treatment Period(Baseline (30 minutes-2 hours) pre-dose and at 8 hours post-dose on Day 1 of each treatment period)
- Time to Onset of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period(Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period)
- Duration of Mean Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period(Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period)
- Number of Participants With Complete Suppression, Partial Response, and no Response of SPR up to 8 Hours Post-dose on Day 1 of Each Treatment Period(Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period)
- Maximum Change From Baseline of Photosensitivity Response in Each of the 3 Eye Conditions (Eye Closure, Eyes Closed, and Eyes Open Condition) up to 8 Hours Post-dose on Day 1 of Each Treatment Period(Baseline (30 minutes-2 hours) pre-dose up to 8 hours post-dose on Day 1 of each treatment period)
- Number of Participants With Clinically Significant Change From Baseline Values For Vital Signs(First dose of study drug (Baseline) up to 28 days after last dose of study drug (Day 71))