BACKGROUND AND PURPOSE: This trial was a double-blind, placebo-controlled, phase 
III trial with an 8-hour inclusion window to assess the efficacy and safety of 
an intravenous loading dose of 7.5 mg followed by a daily intravenous dose of 10 
mg lubeluzole for 5 days in acute ischemic stroke patients.
METHODS: A total of 1786 patients were randomized: 901 to lubeluzole and 885 to 
placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 213 (24.1%) 
from the placebo group discontinued the trial prematurely. In the lubeluzole 
group 201 patients (22.3%) discontinued because of adverse events compared with 
193 patients (21.8%) in the placebo group.
RESULTS: The primary population for the efficacy analysis comprised the core 
stroke patients (exclusion of older patients aged >75 years with severe stroke) 
in the 0- to 6-hour inclusion time window. The primary efficacy parameter was a 
3-category functional status (Barthel Index 70 to 100/0 to 70/vegetative, dead) 
at week 12. In the lubeluzole group 207 patients (47.8%) were classified as 
mildly dependent/independent at week 12, 131 (30.3%) were moderately/severely 
dependent, and 95 (21.9%) were vegetative/dead. In the placebo group these 
numbers were 221 (54.4%), 112 (27.6%), and 73 (18.0%), respectively. Logistic 
regression analysis showed no statistically significant difference between the 
treatment groups (P:=0.162). Additionally, for none of the secondary efficacy 
parameters (mortality at week 12, modified Rankin score, total Barthel score) 
was a statistically significant difference between the lubeluzole and placebo 
groups obtained. There were no statistically significant differences between the 
2 treatments for all treated patients, patients included within the 6- to 8-hour 
window, and patients with severe strokes aged >75 years. Overall, of all treated 
patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) 
with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on 
placebo reported an adverse event during their treatment period or within the 
next 2 days after discontinuation of treatment. The most frequently observed 
adverse events were fever (25.9% lubeluzole; 23.4% placebo), constipation 
(20.2%; 19.7%), and headache (17.6%; 21.2%). Imbalances were found for atrial 
fibrillation (1.8% lubeluzole; 1.1% placebo) and QT prolongation (0.9%; 0.2%).
CONCLUSIONS: This study failed to show an efficacy of lubeluzole in the 
treatment of acute stroke. On the other hand, lubeluzole treatment by the 
current dosage schedule was not associated with a significant safety problem.