Perampanel for Sporadic Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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To investigate the safety and the efficacy of perampanel in patients with sporadic amyotrophic lateral sclerosis

Detailed Description
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To evaluate the effect of peramanel for 48 weeks on progression of disease in subjects with ALS, as measured by ALS Functional Rating Scale-Revised (ALSFRS-R)

Official Title
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Perampanel for Sporadic Amyotrophic Lateral Sclerosis (ALS): A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 2 Trials

Conditions
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ALS

Intervention / Treatment
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* Drug: Perampanel
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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[Eligibility Criteria for Interim Registration] Patients who are able to submit written informed consent. If patients are duly capable of study consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation. Patients who are male or female aged 40 years to 78 years at the time of obtaining informed consent Patients who have clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as specified in the revised El Escorial Airlie House diagnostic criteria. The sum of the 3 respiratory items of the ALSFRS-R must total 12 points or more Patients within 2-year elapsed time period from disease onset at the time of obtaining informed consent Patients who can visit study site for out-patient treatment [Eligibility Criteria for Registration] Subjects who meet the following criteria in addition to the inclusion criteria for the interim registration The progression on score of ALSFRS-R during 12 weeks of observation period must be between -2 and -5 Patients who has not initiated newly introduced riluzole therapy after starting the observation period. Or those who has not received dose escalation or resumed administration of riluzole therapy after previous down titration or discontinuation Patients who has not initiated newly introduced edaravone therapy after starting the observation period Patients who are judged to be eligible for continuation of the study by the investigators [Exclusion Criteria] Patients who underwent tracheostomy. Patients who experienced non-invasive positive pressure ventilation. Patients whose percent-predicted forced vital capacity (%FVC) is ≤80%. Patients with progressive bulbar palsy type. Patients with cognitive impairment, severe disease in the renal, cardiovascular, or hematological system. Patients with hepatic disease. Patients with malignant tumor. Pregnant women or women with a possibility of becoming pregnant. Patients who participated in another clinical study within 12 weeks before starting the observation period. Patients who has initiated perampanel therapy in the past or at present. Patients who are judged to be ineligible for study entry by the investigators.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perampanel 4mg<br>Once daily 4mg of perampanel with dose-escalation tolerable from 2mg to 4mg for 48 weeks | Drug: Perampanel<br>* 4mg/d or 8mg/d<br>* Other names: non-competitive AMAP antagonist;|
| Experimental: Perampanel 8mg<br>Once daily 8mg of perampanel with dose-escalation tolerable from 2mg to 8mg for 48 weeks | Drug: Perampanel<br>* 4mg/d or 8mg/d<br>* Other names: non-competitive AMAP antagonist;|
| Placebo Comparator: Placebo<br>Once daily placebo for control for 48 weeks | Drug: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ALS Functional rating scale |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ALS Functional rating scale |  | 12, 24, 36, and 48 weeks | 
| Manual Muscle Test |  | 12, 24, 36, and 48 weeks | 
| Percent-predicted forced vital capacity |  | 12, 24, 36, and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sporadic ALS, perampanel