Trial Outcomes & Findings for Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT00424463)

Last Updated: 2026-01-06

Results Overview

0=worst; 48=best To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

181 participants

Primary outcome timeframe

baseline (seventh cycle) and at 24 week (twelfth cycle)

Results posted on

2026-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	MCI-186 - Placebo of MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Overall Study STARTED	45	48	88
Overall Study COMPLETED	38	34	72
Overall Study NOT COMPLETED	7	14	16

Reasons for withdrawal

Reasons for withdrawal
Measure	MCI-186 - Placebo of MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Overall Study Adverse Event	2	3	2
Overall Study Physician Decision	0	2	2
Overall Study Withdrawal by Subject	4	2	5
Overall Study Tracheotomy due to worsening of ALS	1	7	6
Overall Study Patient's convenience	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MCI-186 - Placebo of MCI-186 n=45 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Total n=181 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=82 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	38 Participants n=37 Participants	29 Participants n=56 Participants	62 Participants n=82 Participants	129 Participants n=31 Participants
Age, Categorical >=65 years	7 Participants n=37 Participants	19 Participants n=56 Participants	26 Participants n=82 Participants	52 Participants n=31 Participants
Sex: Female, Male Female	12 Participants n=37 Participants	22 Participants n=56 Participants	31 Participants n=82 Participants	65 Participants n=31 Participants
Sex: Female, Male Male	33 Participants n=37 Participants	26 Participants n=56 Participants	57 Participants n=82 Participants	116 Participants n=31 Participants

PRIMARY outcome

Timeframe: baseline (seventh cycle) and at 24 week (twelfth cycle)

Population: "1 patient with diseases other than ALS" and "4 patients with missing data" were excluded from the FAS in the MCI-186 - Placebo of MCI-186group. "5 patients with missing data" were excluded from the FAS in the MCI-186 - MCI-186 group. "14 patients with missing data" were excluded from the FAS in the Placebo of MCI-186 - MCI-186 group.

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=40 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=43 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=74 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Change From Baseline in Revised ALS Functional Rating Scale (ALSFRS-R) Score in Full Analysis Set (FAS) Population at 24 Weeks	-5.5 units on a scale Standard Deviation 4.6	-4.2 units on a scale Standard Deviation 4	-5.4 units on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: 24 weeks (from seventh cycle to twelfth cycle)

Population: "1 patient with diseases other than ALS" was excluded from the FAS in the MCI-186 - Placebo of MCI-186 group.

Any of "death, disability of independent ambulation, loss of upper arm function, tracheotomy, use of respirator, and use of tube feeding" was defined as an event.

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=44 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Number of Participants With Death or a Specified State of Disease Progression death	1 Participants	1 Participants	1 Participants
Number of Participants With Death or a Specified State of Disease Progression disability of independent ambulation	8 Participants	11 Participants	20 Participants
Number of Participants With Death or a Specified State of Disease Progression loss of upper arm function	3 Participants	5 Participants	7 Participants
Number of Participants With Death or a Specified State of Disease Progression tracheotomy	0 Participants	0 Participants	2 Participants
Number of Participants With Death or a Specified State of Disease Progression use of respirator	0 Participants	1 Participants	2 Participants
Number of Participants With Death or a Specified State of Disease Progression use of tube feeding	1 Participants	1 Participants	8 Participants

SECONDARY outcome

Timeframe: baseline (seventh cycle) and at 24 week (twelfth cycle)

Population: "1 patient with diseases other than ALS" and "4 patients with missing data" were excluded from the FAS in the MCI-186 - Placebo of MCI-186group. "6 patients with missing data" were excluded from the FAS in the MCI-186 - MCI-186 group. "19 patients with missing data" were excluded from the FAS in the Placebo of MCI-186 - MCI-186 group.

To investigate the sustainability of effects of edaravone, the analysis focusing on the comparison between the placebo and edaravone groups of patients who had received 6 cycles of edaravone treatment, i.e., the comparison of data from Cycles 7 to 12 between the edaravone-edaravone group and the edaravone-placebo group, was performed.

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=40 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=42 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=69 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Change From Baseline in % Forced Vital Capacity (%FVC) in Full Analysis Set (FAS) Population at 24 Weeks	-10.6 percentage of FVC Standard Deviation 13.16	-12.91 percentage of FVC Standard Deviation 14.97	-10.54 percentage of FVC Standard Deviation 13.21

SECONDARY outcome

Timeframe: 36 weeks (from seventh cycle to fifteenth cycle)

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=45 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Percentage of Participants With Adverse Events	97.8 percentage of participant	91.7 percentage of participant	92 percentage of participant

SECONDARY outcome

Timeframe: 36 weeks (from seventh cycle to fifteenth cycle)

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=45 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Percentage of Participants With Adverse Drug Reactions	4.4 percentage of participant	10.4 percentage of participant	10.2 percentage of participant

SECONDARY outcome

Timeframe: 36 weeks (from seventh cycle to fifteenth cycle)

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=45 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group Urinary glucose	0 percentage of participant	6.3 percentage of participant	3.4 percentage of participant
Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group White blood cell count	11.1 percentage of participant	4.2 percentage of participant	10.2 percentage of participant
Percentage of Participants With Laboratory Tests for Which the Incidence of Abnormal Changes Was 5% or Higher in Either Group Alanine aminotransferase	0 percentage of participant	6.3 percentage of participant	4.5 percentage of participant

SECONDARY outcome

Timeframe: 36 weeks (from seventh cycle to fifteenth cycle)

Outcome measures

Outcome measures
Measure	MCI-186 - Placebo of MCI-186 n=45 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 Participants Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Percentage of Participants With Abnormal Changes in Sensory Examinations Numbness	0 percentage of participant	0 percentage of participant	0 percentage of participant
Percentage of Participants With Abnormal Changes in Sensory Examinations Staggering	0 percentage of participant	2.1 percentage of participant	2.3 percentage of participant
Percentage of Participants With Abnormal Changes in Sensory Examinations Vibratory sensation	0 percentage of participant	0 percentage of participant	0 percentage of participant

Adverse Events

MCI-186 - Placebo of MCI-186

Serious events: 13 serious events

Other events: 43 other events

Deaths: 0 deaths

MCI-186 - MCI-186

Serious events: 25 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo of MCI-186 - MCI-186

Serious events: 39 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trials, Information Desk

Tanabe Pharma Corporation

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	MCI-186 - Placebo of MCI-186 n=45 participants at risk Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection placebo administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	MCI-186 - MCI-186 n=48 participants at risk Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion	Placebo of MCI-186 - MCI-186 n=88 participants at risk Cycles 7 to 12 (6 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion Cycles 13 to 15 (3 cycles) : 2 ampoules of edaravone injection 30 mg administered once daily over 60 minutes by intravenous infusion
Cardiac disorders Cardiac arrest	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Eye disorders Retinal vein occlusion	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Gastrointestinal disorders Colonic polyp	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Gastrointestinal disorders Dysphagia	13.3% 6/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	18.8% 9/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	25.0% 22/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Gastrointestinal disorders Enterocolitis	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Gastrointestinal disorders Gastric ulcer	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Gastrointestinal disorders Stomach discomfort	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
General disorders Abasia	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
General disorders Gait disturbance	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	8.3% 4/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	5.7% 5/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Bronchitis	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Bronchopneumonia	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Catheter site infection	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Diverticulitis	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Herpes zoster	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Infections and infestations Pneumonia	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.3% 2/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Injury, poisoning and procedural complications Head injury	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Injury, poisoning and procedural complications Humerus fracture	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Injury, poisoning and procedural complications Joint sprain	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Injury, poisoning and procedural complications Skin laceration	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	3.4% 3/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	8.9% 4/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	12.5% 6/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	11.4% 10/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Nervous system disorders Dysarthria	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Nervous system disorders Dyslalia	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	6.8% 6/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.4% 2/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	6.2% 3/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.3% 2/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.1% 1/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Respiratory disorder	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	4.2% 2/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	2.3% 2/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.4% 2/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	12.5% 6/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	6.8% 6/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)
Respiratory, thoracic and mediastinal disorders Sputum retention	2.2% 1/45 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	0.00% 0/48 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)	1.1% 1/88 • from baseline (seventh cycle) to 36 weeks (fifteenth cycle)