Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients

Figures & data

Figure 1. Trial profile.

Table I. Subject demographic characteristics.

Item	Placebo (104) n (%)	Edaravone (101) n (%)
Gender
male	69 (66.3)	63 (62.4)
Initial symptom
bulbar	20 (19.2)	18 (17.8)
limb	84 (80.8)	83 (82.2)
Diagnosis (El Escorial revisited)
definite	21 (20.2)	29 (28.7)
probable	54 (51.9)	52 (51.5)
probable laboratory-supported	28 (26.9)	20 (19.8)
possible	1 (1.0)	0 (0.0)
The Japanese severity classification
grade 1	40 (38.5)	36 (35.6)
grade 2	64 (61.5)	65 (64.4)
Use of riluzole
yes	92 (88.5)	90 (89.1)
Change in ALSFRS-R score during pre-observation
−4, −3	32 (30.8)	29 (28.7)
−2, −1	72 (69.2)	72 (71.3)

Item	Placebo (104) median (min-max)	Edaravone (101) median (min-max)
Age (years old)	58.5 (28–75)	58.0 (29–73)
Body weight (kg)	57.0 (37–109)	57.0 (35–77)
Duration of disease (years)	1.20 (0.3–3.0)	1.30 (0.4–2.9)
ALSFRS-R score before pre-observation	44.0 (35–48)	43.0 (31–48)
ALSFRS-R score before treatment period	42.0 (32–47)	41.0 (29–47)

ALSFRS-R: the revised amyotrophic lateral sclerosis functional rating scale.

Table II. Change in endpoints during treatment.

	Change in endpoints during treatment (ANCOVA)				Repeated-measures analysis
	Adjusted mean change LS Mean ± S.E.		Inter-group difference in adjusted mean change LS Mean ± S.E. (95% C.I.)		Adjusted mean LS Mean ± S.E.		Inter-group difference in adjusted mean LS Mean ± S.E. (95% C.I.)
	Placebo	Edaravone		p value	Placebo	Edaravone		p value
Primary endpoint
ALSFRS-R	−6.35 ± 0.84 (99)	−5.70 ± 0.85 (100)	0.65 ± 0.78 (−0.90 – 2.19)	0.411	37.43 ± 0.46	38.08 ± 0.47	0.65 ± 0.44 (−0.22 – 1.52)	0.141
Secondary endpoint
%FVC	−17.49 ± 2.39 (99)	−14.57 ± 2.41 (100)	2.92 ± 2.24 (−1.49, 7.33)	0.193	87.30 ± 1.56	88.56 ± 1.59	1.26 ± 1.46 (−1.63, 4.15)	0.390
Grip strength	−5.71 ± 0.69 (99)	−4.81 ± 0.69 (100)	0.89 ± 0.64 (−0.37, 2.16)	0.165	13.22 ± 0.42	13.83 ± 0.43	0.60 ± 0.40 (−0.18, 1.38)	0.130
Pinch strength	−1.03 ± 0.15 (99)	−0.83 ± 0.15 (100)	0.20 ± 0.14 −0.08, 0.48)	0.165	2.62 ± 0.11	2.83 ± 0.11	0.21 ± 0.10 (0.01, 0.41)	0.038
Modified Norris scale	−16.15 ± 2.00 (97)	−14.12 ± 2.05 (95)	2.03 ± 1.89 (−1.69, 5.75)	0.284	NA	NA	NA	NA
ALSAQ40	19.13 ± 3.79 (95)	19.60 ± 3.82 (95)	0.48 ± 3.50 (−6.44, 7.39)	0.892	NA	NA	NA	NA

ALSFRS-R: interaction between treatment group and period (p = 0.915). ALSFRS-R: the revised amyotrophic lateral sclerosis functional rating scale. NA: not applicable. For Modified Norris scale and ALSAQ40, repeated measures analysis was not conducted

Figure 2. Change of ALSFRS-R score during treatment by diagnostic category. ALSFRS-R: the revised amyotrophic lateral sclerosis functional rating scale.

Table III. Adverse events and serious adverse events.

	AE				SAE
	Placebo (104)		Edaravone (102)		Placebo (104)		Edaravone (102)
Treatment	n	(%)	n	(%)	n	(%)	n	(%)
Total	92	(88.5)	91	(89.2)	24	(23.1)	18	(17.6)
Constipation	17	(16.3)	13	(12.7)
Dysphagia	12	(11.5)	8	(7.8)	11	(10.6)	8	(7.8)
Nasopharyngitis	22	(21.2)	22	(21.6)
Muscular weakness	9	(8.7)	7	(6.9)	1	(1.0)	1	(1.0)
Contusion	5	(4.8)	12	(11.8)
Headache	3	(2.9)	8	(7.8)
Insomnia	10	(9.6)	9	(8.8)
Gait disturbance	16	(15.4)	20	(19.6)	2	(1.9)	3	(2.9)
Eczema	2	(1.9)	7	(6.9)
Glucose urine present	3	(2.9)	6	(5.9)

All AE with an incidence greater than 5% are tabulated by the primary term, MedDRA version 11.1.