The cardiovascular safety of lubeluzole was evaluated in patients with
ischemic stroke in a double-blind, placebo-controlled trial. Forty-si
x patients were randomized to receive a continuous daily infusion of l
ubeluzole 5 mg (loading dose 3.75 mg over 1 h), lubeluzole 10 mg (load
ing dose 7.5 mg over 1 h), or placebo for 5 days within 24 h of stroke
onset. The primary measure of cardiovascular safety was the QTc inter
val, derived from the continuous electrocardiogram (ECG) and measured
during treatment and a 2-day follow-up. Compared with placebo, neither
dosage of lubeluzole had any statistically or clinically relevant eff
ects on the QTc. Neither were there any significant differences among
the three treatment groups in the area under the curve for heart rate,
QT interval, QT dispersion, or QT1c. Lubeluzole did not increase the
frequency of ECG abnormalities. No ventricular fibrillation, ventricul
ar tachycardia, or torsades de pointes were observed in any of the tre
atment groups. During this trial, 3 patients in the placebo group and
2 patients in the lubeluzole 5-mg group died. There were no deaths in
the lubeluzole 10-mg group. Adverse experiences were similar in all th
ree treatment groups except that superficial thrombophlebitis was more
frequent in the lubeluzole IO-mg group. In doses to 10 mg/day, lubelu
zole has a favorable cardiovascular safety profile, as demonstrated by
the lack of clinically relevant effects on heart rate, QT, QTc, and Q
T1c, and it was well tolerated by patients with ischemic stroke.