Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls

Abstract

Objective: To evaluate the impact of lasmiditan, an oral, centrally-penetrant, selective serotonin 1F (5-HT1F) receptor agonist developed for the acute treatment of migraine, on simulated driving. Methods: Healthy adult volunteers enrolled in two randomized, placebo and active comparator-controlled, crossover studies. Study 1 (N = 90) tested lasmiditan (50-, 100-, 200-mg), alprazolam (1-mg), and placebo at 1.5 hr post-dose. Study 2 (N = 68) tested lasmiditan (100-, 200-mg), diphenhydramine (50-mg, administered 2 hr pre-assessments), and placebo at 8, 12 and 24 hr post-dose. Driving performance was assessed using a validated driving simulator employing a 100 km driving scenario. Standard deviation of lateral position (SDLP), a measure of lane position control, was the primary endpoint. Results: Assay sensitivity was confirmed by increased SDLP for active comparators at 1.5- and 8-hr time points. Lasmiditan doses showed significant driving impairment versus placebo at 1.5 hr post-dose. Lasmiditan doses were non-inferior to placebo at 8 hr. Driving impairment was concentration-dependent at 1.5 hr but not at 8 hr. Common adverse events were central nervous system-related and mild-to-moderate in severity. Conclusions: Lasmiditan was associated with impaired simulated driving performance at 1.5 hr post-dose, but showed no clinically meaningful impairment at 8 hr post-dose.