A Study of Lasmiditan on Simulated Driving Performance in Healthy Participants

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Randomized, Subject- and Investigator-Blind, Placebo-Controlled, 4-Period Cross-Over Study Assessing the Duration of Effect of Lasmiditan on Simulated Driving Performance in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lasmiditan
* Drug: Placebo
* Drug: Diphenhydramine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo administered orally in one of four study periods. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: 100 milligrams (mg) Lasmiditan<br>100 mg lasmiditan administered orally in one of four study periods. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;|
| Experimental: 200 mg Lasmiditan<br>200 mg lasmiditan administered orally in one of four study periods. | Drug: Lasmiditan<br>* Administered orally<br>* Other names: LY573144;|
| Active Comparator: Diphenhydramine<br>50 mg diphenhydramine administered orally in one of four study periods. | Drug: Diphenhydramine<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | 8 hours postdose in each dosing period | 
| 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) | 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. | 12 hours postdose in each dose period | 
| 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) | 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. | 24 hours post dose in each dose period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Karolinska Sleepiness Scale (KSS) Score | 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. | 8 hours postdose in each dose period | 
| Karolinska Sleepiness Scale (KSS) Score | 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. | 12 hours postdose in each dose period | 
| Karolinska Sleepiness Scale (KSS) Score | 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. | 24 hours postdose in each dose period | 
| Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test | 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. A measure of recall accuracy A higher score indicates greater processing speed | 8 hours postdose in each dose period | 
| Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test | 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. | 12 hours postdose in each dose period | 
| Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test | 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. | 24 hours postdose in each dose period | 
| Total Number of Collisions | 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). | 8 hours postdose in each dose period | 
| Total Number of Collisions | 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). | 12 hours postdose in each dose period | 
| Total Number of Collisions | 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). | 24 hours postdose in each dose period | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan | PK: 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: Area Under the Concentration Versus Time Curve (AUC) of Lasmiditan to the Last Timepoint (0-tlast) | PK: AUC of Lasmiditan until the last time a concentration is detected. | Day 1: Predose, 0.5 hour (hr), 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr, 10 hr, 12hr, 24hr, 36hr, 48hr postdose |