A Double-Blind, Parallel-Group, Placebo-Controlled, 24-Week, Exploratory Study of Edaravone (MCI-186) for the Treatment of Advanced Amyotrophic Lateral Sclerosis (ALS) (P3.191)

Objective:To explore the possible efficacy of edaravone in ALS patients with more advanced disease, whose impairment excludes independent function (Edaravone MCI-186-18/NCT00415519).

Background: A hypothesis-driven, post hoc subgroup analysis of ALS patients in a phase III trial of edaravone (MCI-186-J16) showed a treatment effect among patients with less functional impairment, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) score.

Design/Methods: Patients (N=25) were enrolled who corresponded to a clinical constellation of ALS severity including: definite, probable, or probable-laboratory-supported ALS (El Escorial/revised Airlie House); Japan ALS severity classification grade 3; percentage forced vital capacity of ≥60[percnt]; duration of disease<3 years at consent; and change in ALSFRS-R score of -1 to -4 points during the 12-week pre-observation period. Treatment consisted of 6 cycles of edaravone 60 mg or matching placebo for 10 of 14 days (cycle 1: 14/14 days) followed by a 14-day drug-free period. Main efficacy endpoint was change in ALSFRS-R score from baseline. Safety endpoints included adverse events (AEs) and laboratory tests.

Results:The mean ±SE change in ALSFRS-R score from baseline was -6.52±1.78 points in the edaravone group and -6.00±1.83 points in the placebo group. The mean between-group difference (placebo-edaravone) change from baseline through cycle 6 was -0.52±2.46 (P=0.835). AEs were experienced by 92.3[percnt] and 100[percnt] of patients in the edaravone and placebo groups, respectively. Serious AE incidence was 23.1[percnt] for edaravone and 16.7[percnt] for placebo. The incidence of adverse drug reactions (ADRs) was 23.1[percnt] for edaravone and 8.3[percnt] for placebo. There were no serious ADRs. Three or more AEs of gait disturbance, pruritus, diarrhea, upper respiratory tract infection, or headache occurred in the edaravone group. One death occurred in the edaravone group due to respiratory failure (worsening of ALS).

Conclusion: No difference between edaravone and placebo treatment was discerned in this exploratory study in patients with more advanced ALS. Disclosure: Dr. Tanaka has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Akimoto has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Palumbo has received personal compensation for activities with Mitsubishi Tanabe Pharma Corporation. Dr. Sakata has received personal compensation for activities with the Mitsubishi Tanabe Pharmaceutical Corporation.