Fig 1.
Study design for edaravone Study 19.
After a 12-week pre-observation period, eligible subjects were randomized to receive either edaravone or placebo during a 24-week, double-blind period. After the double-blind period, subjects received open-label edaravone for 24 weeks. The diagram shows the treatment cycle and corresponding weeks, along with selected inclusion criteria and the primary end point. ALS, amyotrophic lateral sclerosis; ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; E, edaravone; FVC, forced vital capacity; P, placebo.
Fig 2.
The diagram shows subject disposition for the various stages of Study 19 and reasons for discontinuation. Note that for the overall study, subjects who returned for follow-up through cycle 11 were considered to have “completed” the study; however, a total of 5 subjects did not have data available for cycle 12 (2 subjects in the edaravone-edaravone group and 3 in the placebo-edaravone group, as indicated in the figure) and those subjects were excluded from the statistical analyses presented in this study. Adapted with permission [19]. ALS, amyotrophic lateral sclerosis; FVC, forced vital capacity (% of predicted); PaCO2, partial pressure of carbon dioxide in arterial blood.
Table 1.
Baseline demographics and clinical characteristics in Study 19 [11].
Table 2.
Baseline demographics and clinical characteristics in FVC24 subgroups.
Table 3.
FVC values in the analysis subgroups.
Fig 3.
Change in ALSFRS-R scores in FVC24 subgroups.
Change in ALSFRS-R scores (LS means) in the FVC24 ≥80%p and FVC24 <80%p subgroups for baseline to week 24 (BL-W24), week 24 to week 48 (W24-W48), or baseline to week 48 (BL-W48) (edaravone, blue columns; placebo, yellow columns; placebo followed by edaravone, blue columns with yellow dashed outlines). A mixed-effects model for repeated measures (MMRM) analysis was conducted on observed cases. LS mean differences and percentage differences between treatment arms are shown. The subject number included in each analysis is shown in parentheses just above each data column. Note that 5 subjects did not have cycle 12 ALSFRS-R data and were not included in the analysis. ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; BL, baseline; FVC24, forced vital capacity in 24 weeks; LS, least squares; W, week.
Fig 4.
Regression analysis of change from baseline ALSFRS-R scores for the FVC24 ≥80%p subgroup.
Symbols indicate treatment with edaravone (E, blue diamonds), placebo (P, yellow squares), edaravone-edaravone (EE, blue triangles), or placebo-edaravone (PE, blue squares). Data reflect LS mean change from baseline values. Linear regression line equations are shown on the graph. %p, percent of predicted; ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; E, edaravone; FVC24, forced vital capacity in 24 weeks; LS, least squares; P, placebo.
Fig 5.
Regression analysis of change from baseline ALSFRS-R scores for the FVC24 <80%p subgroup.
Symbols indicate treatment with edaravone (E, blue diamonds), placebo (P, yellow squares), edaravone-edaravone (EE, blue triangles), or placebo-edaravone (PE, blue squares). Data reflect LS mean change from baseline values. Linear regression line equations are shown on the graph. ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; E, edaravone; FVC24, forced vital capacity at 24 weeks; LS, least squares; P, placebo.
Fig 6.
ALSFRS-R score vs FVC at week 48.
Graph of ALSFRS-R vs FVC values at week 48. The dashed gray horizontal line delineates an ALSFRS-R score of 24; the black vertical line delineates an FVC value of 80%p. Each triangle represents 1 subject in the edaravone-edaravone group and each square represents one subject in the placebo-edaravone group at week 48. Over a wide range of FVC48%p, a large number of ALS subjects participating in the clinical trial maintained an ALSFRS-R total score at or above 24 throughout the clinical trial period. Linear regression line equation is shown on the graph. %p, percent of predicted; ALS, amyotrophic lateral sclerosis; ALSFRS-R, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; FVC, forced vital capacity.