Determination of the dose proportionality of single intravenous doses (5, 10, and 15 mg) of lubeluzole in healthy volunteers

Abstract

The dose proportionality of lubeluzole, a drug in clinical development for the treatment of acute ischemic stroke, was evaluated in a Phase I, single-center, open-label, randomized-dosing-sequence, three-way crossover clinical trial in 12 healthy adults. An equal number of male and female volunteers were enrolled in the trial, with a mean weight (± SD) of 73.2 ± 11.9 kg, mean height (± SD) of 66.8 ± 4.6 inches, and a mean age of 36.1 ± 5.2 years. Subjects received intravenous infusions of 5 (A), 10 (B), and 15 mg (C) of lubeluzole over 1 hour on three separate occasions, with a minimum washout period of 2 weeks. The treatment sequences were A-B-C; A-C-B; B-A-C; B-C-A; C-A-B; and C-B-A. One male and one female were assigned to each sequence. After the 5-, 10-, and 15-mg doses, maximum concentration (C max) was 58.1, 113, and 138 μg/L, respectively, and the area under the curve from 0 to ∞ (AUC 0−∞) was 771, 1384, and 2025 μg · h/L. There were no statistically significant differences among the groups in mean terminal half-life, steady-state volume of distribution, total plasma clearance, or dose-normalized AUC 0−∞. Dose-normalized values of C max differed significantly between the groups. No serious adverse events were reported, and no changes were observed in cardiac function, as judged by the QT c interval. The pharmacokinetics of lubeluzole appear to be linear at intravenous infusion doses of 5, 10, and 15 mg, and these doses are well tolerated by healthy adults.