Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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This is a long-term, double-blind, placebo-controlled study of MCI-186 to treat ALS. This study is the long-term extension of Study NCT00330681; Study NCT00330681 is a Phase 3, randomized, double-blind, placebo control, parallel assignment, 24-week study in the treatment of ALS. The objectives of this study are to assess the efficacy and safety of long-term intermittent therapy with 60 mg MCI-186 to ALS patients.

Official Title
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An Expanded Controlled Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis in Double-Blind, Parallel-Group, Placebo-Controlled Manner (Phase 3)

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Drug: MCI-186
* Drug: Placebo of MCI-186


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who ware completed drug administration without discontinuation in the preceding confirmatory study NCT00330681. Exclusion Criteria: Patients with such complications as Parkinson's disease, schizophrenia, dementia, renal failure, or other severe complication, and patients who have the anamnesis of hypersensitivity to edaravone. Patients whose creatinine clearance is 50mL/min or less at the time of completion of drug administration in the study NCT00330681. Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant, and patients who can not agree to contraception. Patients who are participating in other clinical trials except the study NCT00330681. In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.

Ages Eligible for Study
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Minimum Age: 20 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: 1<br> | Drug: MCI-186<br>* Two ampoules (60 mg) of MCI-186 injection are intravenously administered once a day for 10 days during 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days ) - observation (14 days) cycle is repeated eight times.<br>* Other names: Radicut;|
| Placebo Comparator: 2<br> | Drug: Placebo of MCI-186<br>* Two ampoules of placebo injection are intravenously administered once a day for 10 days during 14 days, followed by 14 days observation period (first cycle). Then treatment (10 days' administration during 14 days) - observation (14 days) cycle is repeated eight times.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks | 0=worst; 48=best To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed. | baseline (seventh cycle) and at 24 week (twelfth cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death or a Specified State of Disease Progression | Any of death, disability of independent ambulation, loss of upper arm function, tracheotomy, use of respirator, and use of tube feeding was defined as an event. | 24 weeks (from seventh cycle to twelfth cycle) | 
| Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks | To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed. | baseline (seventh cycle) and at 24 week (twelfth cycle) | 
| Percentage of Participants With Adverse Events |  | 36 weeks (from seventh cycle to fifteenth cycle) | 
| Percentage of Participants With Adverse Drug Reactions |  | 36 weeks (from seventh cycle to fifteenth cycle) | 
| Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group |  | 36 weeks (from seventh cycle to fifteenth cycle) | 
| Percentage of Participants With Abnormal Changes in Sensory Examinations |  | 36 weeks (from seventh cycle to fifteenth cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic lateral sclerosis (ALS)