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

• Published in: Human psychopharmacology Vol. 35; no. 5; pp. e2732 - n/a
• Main Authors: Pearlman, Eric M., Wilbraham, Darren, Dennehy, Ellen B., Berg, Paul H., Tsai, Max, Doty, Erin G., Kay, Gary G.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2020; John Wiley and Sons Inc
• Subjects: Adult; Agonists; Alprazolam; Automobile Driving; Benzamides - administration & dosage; Benzamides - adverse effects; Central nervous system; Cross-Over Studies; Diphenhydramine; Dose-Response Relationship, Drug; Double-Blind Method; Driving ability; Female; Headache; Humans; lasmiditan; Male; Middle Aged; Migraine; Piperidines - administration & dosage; Piperidines - adverse effects; Pyridines - administration & dosage; Pyridines - adverse effects; Receptor, Serotonin, 5-HT1F; Receptors, Serotonin - drug effects; selective serotonin receptor agonist; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - adverse effects; Time Factors; Young Adult; lasmiditan; selective serotonin receptor agonist; migraine
• ISSN: 0885-6222; 1099-1077; 1099-1077
• DOI: 10.1002/hup.2732

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.