Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS

Inclusion Criteria:
1. Subjects must provide a signed and dated informed consent form (ICF) to participate in
the study. Subjects must be able (in the judgment of the Investigator) to understand
the nature of the study and all risks involved with participation in the study.
Subjects must be willing to cooperate and comply with all protocol restrictions and
requirements.
2. Subjects will be male or female, ≥ 18 to 75 years of age at the time the ICF is
signed.
3. Subjects will be diagnosed with Definite ALS or Probable ALS according to the El
Escorial revised criteria for the diagnosis of ALS.
4. Subjects with a baseline score ≥ 2 points on each individual item of the ALSFRS- R at
screening and baseline visits.
5. Subjects have a screening and baseline %forced vital capacity (FVC) ≥ 70%.
6. Subjects with 1- to 4-point decline for 8 weeks (±7 days) in ALSFRS-R total score
between screening and baseline visits.
7. Subjects whose first symptom of ALS has occurred within 2 years of providing written
informed consent.
Exclusion Criteria:
Exclusions Related to Primary Diagnosis
1. Subjects with a history of spinal surgery after the onset of ALS, such as surgery for
cervical spondylosis or a herniated disc, or plans for such surgery during the study
period.
Exclusions Related to Other Neurological Disorders (including, but not limited to the
following)
2. Subjects with the possibility that the current symptoms may be symptoms of a disease
requiring differential diagnosis, such as cervical spondylosis and multifocal motor
neuropathy, cannot be ruled out.
Exclusions Related to General Health or Concomitant Conditions
3. Subjects undergoing treatment for a malignancy.
4. Subjects with a complication that could have a significant effect on efficacy
evaluations, such as Parkinson's disease or syndrome, schizophrenia, bipolar disorder,
and dementia.
5. Subjects who have the presence or history of any clinically significant (CS) disease
(except ALS) that could interfere with the objectives of the study (the assessment of
safety and efficacy) or the safety of the subject, as judged by the Investigator.
6. Subjects who are female, of childbearing potential, and pregnant (a positive pregnancy
test) or lactating at the screening visit (Visit 1).
7. Subjects of childbearing potential unwilling to use acceptable method of contraception
from the screening visit until 3 months after the last dose of study medication.
Subjects who are sexually active who do not agree to use contraception during the
study period.
8. Subjects who have a significant risk of suicidality. Subjects with any suicidal
behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to
act, without a specific plan) or type 5 (active suicidal ideation with specific plan
and intent) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the 3
months before the screening visit.
9. Subjects who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
elevations greater than 2 times the upper limit of normal (ULN) at screening.
10. Subjects with a Glomerular Filtration Rate (GFR) < 30 mL/Min Per 1.73 m2 at screening,
using the Larsson Equation.
Exclusions Related to Medications
11. Subjects with history of hypersensitivity to edaravone, any of the additives or
inactive ingredients of edaravone, or sulfites.
12. Subjects with hereditary problems of fructose intolerance (eg, fructose, sucrose,
invert sugar, and sorbitol).
13. Subjects who participated in another study and were administered an investigational
product within 1 month or 5 half-lives of the investigational agent, whichever is
longer, before providing informed consent for the present study.
14. Subjects who have received any previous treatment with edaravone.
15. Subjects who have received stem cell therapy.
16. Subjects who are unable to take their medications orally at baseline (Visit 2).