Table 2

Primary efficacy endpoints analysed in two patient populations

(A) Analysis conducted using data from all participants
 Primary efficacy endpointsPlacebo (n=123)MethylcobalaminCrude p value
(comparison with placebo)
Adjusted p value
(comparison with placebo)
25 mg (n=124)50 mg (n=123)50 mgMethylcobalamin50 mgMethylcobalamin
Time to the primary event*, day
 Median (95% CI)880 (678 to 12171147 (819 to –)954 (777 to –)0.33†0.20†0.15†0.13†
 First quartile (25%) (95% CI)465 (363 to 538)499 (392 to 610)503 (377 to 627)
 Third quartile (75%) (95% CI)–‡–‡
 HR vs the placebo group in each active group (95% CI)0.83 (0.58 to 1.20)0.92 (0.65 to 1.32)
 HR vs the placebo group in total active group (95% CI)0.88 (0.64 to 1.20)
Change in ALSFRS-R score
 Patients, n123124122
 Median (min, max)−24.0 (−42, −1)−22.0 (−42, 2)−21.0 (−39, 1)0.15§0.09§0.18§0.19§
 First quartile (25%)−30.0−30.5−27.0
 Third quartile (75%)−16.0−12.5−10.0
(B) Analysis conducted using data from the subgroup of patients diagnosed early (≤12 months after symptom onset)
 Primary efficacy endpointsPlaceboMethylcobalaminP value (comparison with placebo)
25 mg50 mg50 mgMethylcobalamin
Time to primary event*, day
 Median (95% CI)570 (465 to 720)1087 (564 to –)1197 (609 to –)0.01†0.01†
 First quartile (25%) (95% CI)363 (201 to 491)410 (304 to 594)448 (337 to 1062)
 Third quartile (75%) (95% CI)925 (709 to –)– (1186)– (–, –)¶
 HR vs the placebo group in each active group (95% CI)0.64 (0.38 to 1.09)0.50 (0.27 to 0.93)
 HR vs the placebo group in total active group (95% CI)0.57 (0.35 to 0.92)
Change in ALSFRS-R score
 Patients, n485441
 Median (min, max)−26.5 (−40, −3)−26.5 (−40, 0)−22.0 (−38, 1)0.003§0.01§
 First quartile (25%)−32.5−32.0−27.0
 Third quartile (75%)−20.0−19.0−9.0
  • *Primary events defined as death for any cause or invasive or non-invasive ventilation support for ≥22 hours due to ALS progression.

  • †Intergroup difference analysed using log-rank score.

  • ‡Third quartile of the primary event-free survival was not calculable in any of the groups.

  • §Intergroup difference analysed using Wilcoxon score.

  • ¶Third quartile of time to the primary event was not calculable in the 50 mg methylcobalamin group.

  • ALS, amyotrophic lateral sclerosis; ALSFRS-R, Revised ALS Functional Rating Scale.