Dataset Information

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.

SUBMITTER: Pearlman EM

PROVIDER: S-EPMC7539914 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pearlman Eric M EM Wilbraham Darren D Dennehy Ellen B EB Berg Paul H PH Tsai Max M Doty Erin G EG Kay Gary G GG

Human psychopharmacology 20200525 5

<h4>Objective</h4>To evaluate the impact of lasmiditan, an oral, centrally-penetrant, selective serotonin 1F (5-HT<sub>1F</sub> ) receptor agonist developed for the acute treatment of migraine, on simulated driving.<h4>Methods</h4>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-m ...[more]

PMID: 32449213

Similar Datasets

Project description:ObjectiveDaily cannabis users develop tolerance to some drug effects, but the extent to which this diminishes driving impairment is uncertain. This study compared the impact of acute cannabis use on driving performance in occasional and daily cannabis users using a driving simulator.MethodsWe used a within-subjects design to observe driving performance in adults age 25 to 45 years with different cannabis use histories. Eighty-five participants (43 males, 42 females) were included in the final analysis: 24 occasional users (1 to 2 times per week), 31 daily users and 30 non-users. A car-based driving simulator (MiniSim™, National Advanced Driving Simulator) was used to obtain two measures of driving performance, standard deviation of lateral placement (SDLP) and speed relative to posted speed limit, in simulated urban driving scenarios at baseline and 30 min after a 15 min ad libitum cannabis smoking period. Participants smoked self-supplied cannabis flower product (15% to 30% tetrahydrocannabinol (THC). Blood samples were collected before and after smoking (30 min after the start of smoking). Non-users performed the same driving scenarios before and after an equivalent rest interval. Changes in driving performance were analyzed by repeated measures general linear models.ResultsMean whole blood THC cannabinoids concentrations post smoking were use THC = 6.4 ± 5.6 ng/ml, THC-COOH = 10.9 ± 8.79 ng/mL for occasional users and THC = 36.4 ± 37.4 ng/mL, THC-COOH = 98.1 ± 90.6 ng/mL for daily users. On a scale of 0 to 100, the mean post-use score of subjective high was similar in occasional users and daily users (52.4 and 47.2, respectively). In covariate-adjusted analysis, occasional users had a significant increase in SDLP in the straight road segment from pre to post compared to non-users; non-users decreased by a mean of 1.1 cm (25.5 cm to 24.4 cm) while occasional users increased by a mean of 1.9 cm (21.7 cm to 23.6 cm; p = 0.02). Daily users also increased adjusted SDLP in straight road segments from baseline to post-use (23.2 cm to 25.0 cm), but the change relative to non-users was not statistically significant (p = 0.08). The standardized mean difference in unadjusted SDLP from baseline to post-use in the straight road segments comparing occasional users to non-users was 0.64 (95% CI 0.09 - 1.19), a statistically significant moderate increase. When occasional users were contrasted with daily users, the baseline to post changes in SDLP were not statistically significant. Daily users exhibited a mean decrease in baseline to post-use adjusted speed in straight road segments of 1.16 mph; a significant change compared to slight speed increases in the non-users and occasional users (p = 0.02 and p = 0.01, respectively).ConclusionWe observed a decrement in driving performance assessed by SDLP after acute cannabis smoking that was statistically significant only in the occasional users in comparison to the nonusers. Direct contrasts between the occasional users and daily users in SDLP were not statistically significant. Daily users drove slower after cannabis use as compared to the occasional use group and non-users. The study results do not conclusively establish that occasional users exhibit more driving impairment than daily users when both smoke cannabis ad libitum.

Project description:SignificanceThe first contact lens to incorporate a photochromic additive was cleared by the U.S. Food and Drug Administration last year. Because any ophthalmic lens that absorbs visible wavelengths will reduce retinal illuminance, it is important to understand the impact of this new photochromic contact lens on vision and both daytime and nighttime driving performance.PurposeThe purpose of this study was to evaluate the effect of senofilcon A photochromic contact lens wear on vision and driving performance under real-world conditions by comparison with a nonphotochromic contact lens and plano photochromic spectacles.MethodsIn this randomized four-visit bilateral crossover study, 24 licensed regular drivers and established wearers of soft contact lenses were enrolled. Subjects wore in random order each of three study lens types: the investigational photochromic soft contact lens (test), a nonphotochromic soft contact lens (control 1), and plano photochromic spectacle lenses (control 2). Driver performance was assessed on a closed-circuit driving track under challenging controlled conditions. The primary endpoint was overall driving performance score calculated as a composite Z score of six objective metrics.ResultsAll 24 subjects (mean age, 29.8 years) completed the study. For nighttime driving, the adjusted mean differences in Z score (95% confidence interval) between test and control 1 and between test and control 2 were 0.069 (-0.045 to +0.183) and 0.117 (0.003 to 0.231), respectively. For daytime driving, mean differences were 0.101 (-0.013 to +0.216) between test and control 1 and 0.044 (-0.070 to +0.158) between test and control 2. Results demonstrated noninferiority of the test lens relative to controls for nighttime and daytime driving performance using a noninferiority margin of -0.25 Z score. Noninferiority was also demonstrated on all logMAR and contrast threshold testing. No adverse events were reported during the study.ConclusionsStudy results revealed no evidence of concerns with either driving performance or vision while wearing photochromic contact lenses.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets