A Study of Lasmiditan on Simulated Driving Performance in Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Lasmiditan
Drug: Placebo
Drug: Diphenhydramine

Registration Number: NCT03459612

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to evaluate the effect of lasmiditan on simulated driving performance in healthy participants. Participants are expected to complete each of four study periods, which will last a total of about 10 days. During this time, participants will remain in the clinical research unit. Screening must be completed within 28 days before the start of the study. Follow-up will be completed about one week after discharge.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

Inclusion Criteria

Are overtly healthy males or females, as determined through medical history and physical examination.
Possess a valid driver's license and is an active driver at screening. Driven a minimum of 8,000 miles (about 13,000 kilometers) per year for the preceding 3 years.
Have a score of <10 on the Epworth Sleepiness Scale.

Exclusion Criteria

Have a history within 3 months of admission, or current treatment for, a sleeping disorder (including excessive snoring, obstructive sleep apnea), or a chronic painful condition that interferes with the subject's sleep.
Have a history of difficulty either falling asleep or staying asleep in the previous 3 months of admission that is considered clinically significant by the investigator.
Are expected to use any other medication or dietary supplement to promote sleep including over the-counter sleep medications, during their participation in the study.
Have traveled across 2 or more time zones (transmeridian travel) in the past 2 weeks prior to randomization.
Have worked in a night shift in the past 2 weeks prior to randomization.
Show a history of central nervous system (CNS) conditions such as strokes, transient ischemic attacks, significant head trauma, seizures, CNS infections, migraine, brain surgery, or any other neurological conditions that, in the opinion of the investigator, increase the risk of participating in the study.
Show evidence of significant active neuropsychiatric disease (e.g., manic depressive illness, schizophrenia, depression) considered as clinically significant by the investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
100 milligrams (mg) Lasmiditan	Lasmiditan	100 mg lasmiditan administered orally in one of four study periods.
200 mg Lasmiditan	Lasmiditan	200 mg lasmiditan administered orally in one of four study periods.
Placebo	Placebo	Placebo administered orally in one of four study periods.
Diphenhydramine	Diphenhydramine	50 mg diphenhydramine administered orally in one of four study periods.

Primary Outcome Measures

Name	Time	Method
Simulated Driving Performance in Healthy Participants as Measured by Standard Deviation of Lateral Position (SDLP) Using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim)	24 hours post dose in each dose period	The standard deviation of lateral position (SDLP) is the primary parameter used as stable measure of driving performance with high test-retest reliability. It measures the driver's ability to stay in a constant position within the driving lane. LS Means were analyzed using a mixed repeated measures model with fixed effects for sequence, period, and treatment, with repeated observations for subjects for each of the driving time points.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan	Day 1: Predose, 0.5 hour (hr), 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr, 10 hr, 12hr, 24hr, 36hr, 48hr postdose	PK: Cmax of Lasmiditan
PK: Area Under the Concentration Versus Time Curve (AUC) of Lasmiditan to the Last Timepoint (0-tlast)	Day 1: Predose, 0.5 hour (hr), 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr, 10 hr, 12hr, 24hr, 36hr, 48hr postdose	PK: AUC of Lasmiditan until the last time a concentration is detected.
Karolinska Sleepiness Scale (KSS) Score	24 hours postdose in each dose period	The KSS is used to assess subjective level of sleepiness. This is a participant self-report measure of situational sleepiness and provides an assessment of alertness/sleepiness at a particular point in time. It is a 9-point categorical Likert scale on which the participant rates sleepiness from 1 (very alert) to 9 (very sleepy/fighting sleep), with higher scores indicating more sleepiness and lower scores indicating more alertness.
Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test	24 hours postdose in each dose period	The SDC Test, a digit symbol substitution test that is sensitive to changes in information processing speed, provides measures of response speed and accuracy. The test was administered prior to the simulated driving sessions. The principal test score measures the number of correct responses in 120 seconds. SDC was used in this study to measure attention, visual scanning, working memory, and speed of information processing. Scores range from 0 (No correct responses). A higher score indicates greater processing speed.
Total Number of Collisions	24 hours postdose in each dose period	Total collisions are the sum off collisions with other vehicles and off-road crashes. Collision counts also included the number of times that a lane deviation exceeded 4 feet but where no collision occurred ( a crash-likely event).