Trial Outcomes & Findings for Arimoclomol in Amyotropic Lateral Sclerosis (NCT NCT03491462)

Last Updated: 2023-08-24

Results Overview

Combined Assessment of Function and Survival (CAFS) is a composite endpoint that includes 1) the change from baseline in revised ALS functional rating scale (ALSFRS-R) and 2) the survival endpoint (time to permanent assisted ventilation \[PAV\], tracheostomy or death). On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time to PAV, tracheostomy, or death the better outcome. A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to event (PAV, tracheostomy, or death) to the outcome for all other patients in the study in a pairwise fashion. A higher rank score (range 0-1) is considered a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

245 participants

Primary outcome timeframe

Over 76 Weeks

Results posted on

2023-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Arimoclomol (up to 76 Weeks) Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) Matching placebo 3 times daily for up to 76 weeks
Overall Study STARTED	160	79
Overall Study COMPLETED	122	63
Overall Study NOT COMPLETED	38	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Arimoclomol (up to 76 Weeks) Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) Matching placebo 3 times daily for up to 76 weeks
Overall Study Lost to Follow-up	2	0
Overall Study Adverse Event	11	1
Overall Study Physician Decision	3	0
Overall Study Withdrawal by Subject	22	15

Baseline Characteristics

Arimoclomol in Amyotropic Lateral Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arimoclomol (up to 76 Weeks) n=160 Participants Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 Participants Matching placebo 3 times daily for up to 76 weeks	Total n=239 Participants Total of all reporting groups
Age, Continuous	58.0 years STANDARD_DEVIATION 11.26 • n=5 Participants	56.6 years STANDARD_DEVIATION 9.97 • n=7 Participants	57.6 years STANDARD_DEVIATION 10.85 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	34 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	45 Participants n=7 Participants	151 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants n=5 Participants	64 Participants n=7 Participants	196 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	136 Participants n=5 Participants	66 Participants n=7 Participants	202 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	11 Participants n=7 Participants	34 Participants n=5 Participants
Revised ALS Functional Rating Scale (ALSFRS-R)	40.6 units on a scale STANDARD_DEVIATION 3.93 • n=5 Participants	40.2 units on a scale STANDARD_DEVIATION 3.65 • n=7 Participants	40.5 units on a scale STANDARD_DEVIATION 3.83 • n=5 Participants
Percent (%) Predicted Slow Vital Capacity (SVC)	95.8 percent (%) predicted SVC STANDARD_DEVIATION 15.98 • n=5 Participants	98.1 percent (%) predicted SVC STANDARD_DEVIATION 14.78 • n=7 Participants	96.5 percent (%) predicted SVC STANDARD_DEVIATION 15.60 • n=5 Participants

PRIMARY outcome

Timeframe: Over 76 Weeks

Population: modified intention-to-treat (mITT)

Outcome measures

Outcome measures
Measure	Arimoclomol (up to 76 Weeks) n=160 Participants Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 Participants Matching placebo 3 times daily for up to 76 weeks
Combined Assessment of Function and Survival (CAFS)	0.51 score on a scale Standard Deviation 0.291	0.49 score on a scale Standard Deviation 0.283

SECONDARY outcome

Timeframe: Over 76 weeks

Population: modified intention-to-treat (mITT)

Time from baseline to one of the events (PAV / tracheostomy / death). PAV is defined as the first of 7 consecutive days on which PAV was used for \>22 hours/day

Outcome measures

Outcome measures
Measure	Arimoclomol (up to 76 Weeks) n=160 Participants Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 Participants Matching placebo 3 times daily for up to 76 weeks
Time to Permanent Assisted Ventilation (PAV) / Tracheostomy / Death	NA days Interval 479.0 to Median and 3rd Quartile was not estimable due to an insufficient number of participants with events	NA days Interval 466.0 to Median and 3rd Quartile was not estimable due to an insufficient number of participants with events

SECONDARY outcome

Timeframe: Week 76 (or end of trial)

Population: modified intention-to-treat (mITT)

The ALSFRS-R score is based on a rating scale where 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items). The higher the score the better functioning.

Outcome measures

Outcome measures
Measure	Arimoclomol (up to 76 Weeks) n=160 Participants Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 Participants Matching placebo 3 times daily for up to 76 weeks
Change From Baseline to Week 76 (or End-of-trial) in the Revised ALS Functional Rating Scale (ALSFRS-R)	-15.4 units on a scale Standard Deviation 8.71	-15.0 units on a scale Standard Deviation 9.10

SECONDARY outcome

Timeframe: Week 76 (or end of trial)

Population: modified intention-to-treat (mITT)

Slow Vital Capacity (SVC) is a measure of breathing function. SVC measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. The percent (%) of predicted SVC is reported.

Outcome measures

Outcome measures
Measure	Arimoclomol (up to 76 Weeks) n=160 Participants Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 Participants Matching placebo 3 times daily for up to 76 weeks
Change From Baseline to Week 76 (or End-of-trial) in Percent (%) Predicted Slow Vital Capacity (SVC)	-30.65 percent (%) predicted SVC Standard Deviation 26.346	-30.38 percent (%) predicted SVC Standard Deviation 23.839

Adverse Events

Arimoclomol (up to 76 Weeks)

Serious events: 36 serious events

Other events: 149 other events

Deaths: 29 deaths

Placebo (up to 76 Weeks)

Serious events: 20 serious events

Other events: 71 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Affairs

Zevra Denmark A/S

Phone: +1-888-289-5607

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	Arimoclomol (up to 76 Weeks) n=160 participants at risk Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 participants at risk Matching placebo 3 times daily for up to 76 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.4% 7/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Pneumonia	2.5% 4/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Respiratory tract infection	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Bronchitis	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Diverticulitis	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Infection	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Influenza	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Lower respiratory tract infection	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Lung infection	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Cardiac disorders Myocardial infarction	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Cardiac disorders Acute coronary syndrome	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Cardiac disorders Acute myocardial infarction	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Cardiac disorders Cardiac arrest	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Cardiac disorders Cardiac failure acute	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Forearm fracture	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Injury	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Procedural complication	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Investigations Hepatic enzyme increased	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Investigations Transaminases increased	1.2% 2/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Investigations Medical observation	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Vascular disorders Deep vein thrombosis	1.9% 3/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Vascular disorders Circulatory collapse	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Vascular disorders Phlebitis	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Nervous system disorders Cerebrovascular accident	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Nervous system disorders Paraesthesia	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Nervous system disorders Transient ischaemic attack	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Constipation	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Oesophageal perforation	0.00% 0/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	1.3% 1/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
General disorders Medical device site inflammation	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
General disorders Non-cardiac chest pain	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
General disorders Sudden death	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Psychiatric disorders Anxiety	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Psychiatric disorders Assisted suicide	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	0.00% 0/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.

Other adverse events
Measure	Arimoclomol (up to 76 Weeks) n=160 participants at risk Arimoclomol base 248 mg 3 times daily for up to 76 weeks	Placebo (up to 76 Weeks) n=79 participants at risk Matching placebo 3 times daily for up to 76 weeks
Nervous system disorders Headache	21.2% 34/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	26.6% 21/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Fall	20.6% 33/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	21.5% 17/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Constipation	20.0% 32/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	12.7% 10/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Psychiatric disorders Insomnia	14.4% 23/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	8.9% 7/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Nausea	16.9% 27/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	3.8% 3/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Nasopharyngitis	8.8% 14/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	19.0% 15/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Diarrhoea	10.0% 16/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	10.1% 8/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Pneumonia	6.2% 10/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	3.8% 3/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Musculoskeletal and connective tissue disorders Back pain	8.8% 14/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	8.9% 7/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Nervous system disorders Dizziness	10.0% 16/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
General disorders Oedema peripheral	9.4% 15/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Urinary tract infection	7.5% 12/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	8.9% 7/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	6.2% 10/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	7.6% 6/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 10/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Psychiatric disorders Depression	5.0% 8/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	8.9% 7/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Influenza	6.2% 10/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 10/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Contusion	5.6% 9/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 11/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Infections and infestations Bronchitis	3.8% 6/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Investigations Alanine aminotransferase increased	5.6% 9/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Dyspepsia	3.8% 6/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
General disorders Fatigue	5.6% 9/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.4% 7/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Skin and subcutaneous tissue disorders Rash	5.6% 9/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	2.5% 2/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Abdominal pain	3.1% 5/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Injury, poisoning and procedural complications Procedural pain	3.1% 5/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Flatulence	2.5% 4/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Vascular disorders Hypertension	2.5% 4/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Psychiatric disorders Sleep disorder	1.9% 3/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	5.1% 4/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.62% 1/160 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.	6.3% 5/79 • From first dose of study medication up to 76 weeks. Assessed every week. The safety population included all participants not on edaravone at baseline who received any amount of study medication. The safety analysis included all events occurring during the on-treatment observation period which started at the date of first administration of study medication and until 14 days following the latest administration of study medication (in case of interruption of treatment) or last dose of study medication, or end of trial, whichever is earliest.