A Randomized, Double-blind, Placebo-controlled, Parallel-group Study With an Open-label Extension Phase to Evaluate the Effect of Perampanel (E2007) on Cognition, Growth, Safety, Tolerability, and Pharmacokinetics When Administered as an Adjunctive Therapy in Adolescents (12 to Less Than 18 Years of Age) With Inadequately Controlled Partial-onset Seizures
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 133
- 主要终点
- Change From Baseline to Week 19 in Cognition Drug Research (CDR) System Global Cognition Score (Core Study)
研究概览
简要总结
This study is designed to investigate the short- and long-term effects of perampanel on cognition, growth, and development in adolescents.
详细描述
This study consisted of the Core Study and the Extension Part A and B. The Core Study consisted of 2 phases: Prerandomization and Randomization. The Prerandomization Phase lasted up to 1 week, during which participants were assessed for their eligibility to participate in the study. The Randomization Phase consisted of 3 periods: Titration (6 weeks), Maintenance (13 weeks), and Follow-up (4 weeks; only for those participants not rolling over into the Extension Phase). During the Core Study Titration and Maintenance Periods, participants were randomized into perampanel (2 to 12 mg per day) or placebo treatment groups in a 2:1 ratio within each of the age-matched categories (ie, greater than or equal to 12 to less than 15 and greater than or equal to 15 to less than 18).
The extension phase consisted of part A (Conversion Period - 6 weeks and Maintenance period - 25 weeks) and Part B (Optional Extension Phase -52 weeks). The maximum duration for participation in Part B was 52 weeks.
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
- None
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Considered reliable and willing to be available for the study duration and was able to record seizures and report adverse events (AEs) themselves or had a legal guardian or a caregiver who could record seizures and report AEs for them.
- •Understand the requirements of the Cognitive Drug Research (CDR) System tests and able to perform the tests appropriately at Visit
- •Male or female, 12 to less than 18 years of age at the time of consent/assent
- •Had a diagnosis of epilepsy with partial-onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy's (ILAE) Classification of Epileptic Seizures (1981).
- •Diagnosis was established at least 6 months prior to Visit 1, by clinical history and an electroencephalogram (EEG) that was consistent with localization-related epilepsy; normal interictal EEGs were allowed provided that the subject met the other diagnosis criterion (ie, clinical history).
- •Had a brain imaging (e.g., magnetic resonance imaging [MRI] scan or computed tomography [CT]) within the 5 years prior to Visit 1 that ruled out a progressive cause of epilepsy.
- •Had at least 1 partial-onset seizure during the 4 weeks prior to Visit 1 despite a stable regimen of 1 to 3 concomitant antiepileptic drugs (AEDs).
- •Were currently being treated with stable doses of 1-3 AEDs. Only 1 inducer AED (either carbamazepine or phenytoin) out of the maximum of 3 AEDs was allowed.
- •Were on a stable dose of the same concomitant AED(s) for at least 4 weeks prior to Visit 1; in the case where a new AED regimen was initiated for a subject, the dose must have been stable for at least 8 weeks prior to Visit
- •Female subjects of childbearing potential must had a negative serum human chorionic gonadotropin (beta-hCG) at Visit 1 and a negative urine pregnancy test prior to randomization at Visit
- •Female subjects of period of at least 60 days following administration of the last dose of study medication to commit to the consistent and correct use of a medically acceptable method of birth control (e.g., a double-barrier method [condom + spermicide, condom + diaphragm with spermicide]). Abstinence was considered an acceptable method of contraception on a case by case basis upon prior approval by the Medical Monitor.
- •Had an intelligence quotient (IQ) of greater than or equal to 70, using the Kaufman Brief Intelligence Test, second edition (KBIT-2).
- •Provided written informed consent signed by the legal guardian and a written assent from the subject prior to entering the study or undergoing any study procedures.
- •Extension Phase:
- •Had completed all scheduled visits up to and including Visit 8 in the Core Study Randomization Phase.
排除标准
- •Had a diagnosis of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies.
- •Had current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) within approximately 5 years prior to Visit
- •Had a diagnosis of Lennox-Gastaut syndrome.
- •Had seizure clusters where individual seizures could not be counted.
- •Had a history of status epilepticus that required hospitalization during the 12 months prior to the Visit
- •Had an unstable psychiatric diagnosis that could confound the investigator's ability to conduct the study or that could prevent completion of the protocol specified tests (e.g., significant suicide risk, including suicidal behavior and ideation 6 months prior to Visit 1, current psychotic disorder, or acute mania).
- •Had any concomitant illnesses/co-morbidities (e.g., autism, attention deficit hyperactivity disorder [ADHD]) at Visit 1 that could severely affect cognitive function during the course of the study.
- •Had previously participated in a clinical trial involving perampanel.
- •Had chronically or routinely use benzodiazepines and who have not discontinued the use at least 4 weeks prior to Visit 1.
研究组 & 干预措施
Perampenal (Core Study)
Participants received perampanel 2 mg per day and up-titrated weekly in 2-mg increments to a target dose range of 8 to 12 mg per day.
干预措施: Perampanel (Drug)
Placebo (Core Study)
Participants received matching placebo tablets once a day (6 tablets of placebo).
干预措施: Placebo (Drug)
Perampanel (Extension Phase)
During the Extension Phase, participants previously assigned to perampanel arm (Core Study) continued taking study medication at the dose achieved at the end of the Core Study once daily. Participants previously assigned to a placebo arm (Core Study) started perampanel dose at 2 mg/day and up-titrated weekly in 2-mg increments up to a maximum dose of 12 mg/day.
干预措施: Perampanel (Drug)
结局指标
主要结局
Change From Baseline to Week 19 in Cognition Drug Research (CDR) System Global Cognition Score (Core Study)
时间窗: Baseline (Visit 2/Week 0 Evaluation) and Week 19 LOCF (last observation carried forward)
The CDR System Global Cognitive score was derived from the average of 5 CDR System cognitive domain scores (Power of Attention, Continuity of Attention, Quality of Episodic Memory, Quality of Working Memory, and Speed of Memory). The domain scores were normalized to mean of 50 and standard deviation of 10 before taking the average. The scale ranged from 0 - 100. An increase in the Global Cognitive Score indicates improvement, while a decrease indicates worsening in cognitive function.
次要结局
- Number of Participants Who Achieved Seizure-Free Status During the Maintenance Period and the Last 28 Days of the Maintenance Period During the Randomization Phase (Core Study)(13 Week Maintenance Period)
- Percent Change From Baseline in Seizure Frequency Per 28 Days Over the Perampanel Duration Exposure (Extension Phase)(Week 1-13, Week 14-26, Week 27-39, and Week 40-52)
- Change From Baseline at Week 19 in the Power of Attention T-score in the Randomization Phase (Core Study)(Baseline and Week 19)
- Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency (Core Study)(From Baseline up to Week 19 LOCF)
- Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Duration of the Randomization Phase (Core Study)(Baseline and Week 19 LOCF)
- Change From Baseline at Week 19 in the Continuity of Attention T-score in the Randomization Phase (Core Study)(Baseline and Week 19)
- Change From Baseline at Week 19 in the Quality of Episodic Secondary Memory T-score in the Randomization Phase (Core Study)(Baseline and Week 19)
- Change From Baseline at Week 19 in the Quality of Working Memory (Short Term) T-score in the Randomization Phase (Core Study)(Baseline and Week 19)
- Change From Baseline at Week 19 in the Speed of Memory T-score in the Randomization Phase (Core Study)(Baseline and Week 19)
- Percentage of Participants Who Experienced 50% or More Decrease in Seizure Frequency Over the Perampanel Duration Exposure (Extension Phase)(Week 1-13, Week 14-26, Week 27-39, and Week 40-52)
- Mean Change From Baseline to End of Treatment in Cognition Drug Research (CDR) System Global Cognition Score (Extension Phase)(Baseline, Week 9, Week 19, Week, 30, Week 39, Week 52, and End of Treatment (defined as the last nonmissing value after date of first perampanel dose up to 14 days after date of last dose))
- Mean Change From Baseline in CDR System Global Cognition Score Over Time (Extension Phase)(Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52)
- Mean Change From Baseline by Visits in CDR System Domain T-Scores (Extension Phase)(Baseline, Week 9, Week 19, Week 30, Week 39, Week 52, and EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose))
- Mean Change From Baseline in CDR System Domain T-Score Over Time: Power of Attention (Extension Phase)(Baseline, Week 9, Week 19, Week 30, Week 39, and Week 52)
- Mean Change From Baseline in CDR System Domain T-Score Over Time: Continuity of Attention (Extension Phase)(Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52)
- Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Episodic Secondary Memory (Extension Phase)(Baseline, Week 9, Week 19, Week 30, Week 39, and Week 52)
- Mean Change From Baseline in CDR System Domain T-Score Over Time: Quality of Working Memory (Short Term) (Extension Phase)(Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52)
- Mean Change From Baseline in CDR System Domain T-Score Over Time: Speed of Memory (Extension Phase)(Baseline, Week 9, Week 19, Week, 30, Week 39, and Week 52)
- Change From Baseline to End of Treatment in Controlled Oral Word Association Test Scores (COWAT) (Extension Phase)(From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose))
- Change From Baseline to End of Treatment in Time to Complete Lafayette Grooved Pegboard Test (LGPT) (Extension Phase)(From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose))
- Mean Change From Baseline in Bone Age Minus Age (Months) From Hand X-ray (Extension Phase)(From Baseline up to Week 52 or up to EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose))
- Change From Baseline to End of Treatment (EOT) for the Tanner Stage(From Baseline up to Week 52 or EOT (defined as the last nonmissing value after date of first dose up to 14 days after date of last dose))