A Study of Lasmiditan on Simulated Driving Performance in Healthy Participants

• Lasmiditan (Drug), also known as LY573144: Administered orally
• Placebo (Drug): Administered orally
• Diphenhydramine (Drug): Administered orally

Primary outcomes

• 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) [8 hours postdose in each dosing 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.
• 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) [12 hours postdose 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.
• 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 outcomes

• Karolinska Sleepiness Scale (KSS) Score [8 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.
• Karolinska Sleepiness Scale (KSS) Score [12 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.
• 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 [8 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. A measure of recall accuracy A higher score indicates greater processing speed
• Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test [12 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.
• 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 [8 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).
• Total Number of Collisions [12 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).
• 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).
• 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.

Sex: All, ages: 21 Years to 50 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• 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) (Primary), Least squares mean, centimeters: Placebo 29.85 (19.7 to 49.0); 100 mg Lasmiditan 30.83 (18.9 to 52.7); 200 mg Lasmiditan 31.61 (21.6 to 49.3); 50 mg Diphenhydramine 34.83 (19.2 to 62.5) (p <0.0001)
• 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) (Primary), Least squares mean, centimeters: Placebo 30.41 (18.4 to 54.6); 100 mg Lasmiditan 30.29 (19.1 to 50.4); 200 mg Lasmiditan 30.09 (19.9 to 48.6); 50 mg Diphenhydramine 34.72 (19.7 to 56.2) (p <0.0001)
• 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) (Primary), Least squares mean, centimeters: Placebo 32.04 (18.5 to 57.5); 100 mg Lasmiditan 31.07 (18.6 to 54.8); 200 mg Lasmiditan 31.00 (19.9 to 55.7); 50 mg Diphenhydramine 36.10 (19.3 to 66.7) (p <0.0001)
• Karolinska Sleepiness Scale (KSS) Score (Secondary), Mean, Units on a scale: Placebo 3.19 +/- 1.61; 100 mg Lasmiditan 3.46 +/- 1.65; 200 mg Lasmiditan 3.90 +/- 1.78; 50 mg Diphenhydramine 3.93 +/- 1.76
• Karolinska Sleepiness Scale (KSS) Score (Secondary), Mean, units on a scale: Placebo 3.43 +/- 1.57; 100 mg Lasmiditan 3.94 +/- 1.62; 200 mg Lasmiditan 3.79 +/- 1.74; 50 mg Diphenhydramine 4.74 +/- 2.05
• Karolinska Sleepiness Scale (KSS) Score (Secondary), Mean, units on a scale: Placebo 4.19 +/- 2.02; 100 mg Lasmiditan 3.72 +/- 1.69; 200 mg Lasmiditan 3.93 +/- 2.13; 50 mg Diphenhydramine 4.75 +/- 2.15
• Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test (Secondary), Mean, Correct responses: Placebo 69.48 +/- 11.32; 100 mg Lasmiditan 69.76 +/- 10.17; 200 mg Lasmiditan 68.88 +/- 11.27; 50 mg Diphenhydramine 69.01 +/- 11.21
• Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test (Secondary), Mean, Correct responses: Placebo 71.33 +/- 11.26; 100 mg Lasmiditan 70.91 +/- 9.87; 200 mg Lasmiditan 72.16 +/- 9.91; 50 mg Diphenhydramine 68.21 +/- 10.04
• Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test (Secondary), Mean, Correct responses: Placebo 70.78 +/- 9.84; 100 mg Lasmiditan 70.53 +/- 10.52; 200 mg Lasmiditan 70.66 +/- 10.24; 50 mg Diphenhydramine 68.31 +/- 10.27
• Total Number of Collisions (Secondary), Mean, collisions: Placebo 0.1 +/- 0.2; 100 mg Lasmiditan 0.0 +/- 0.2; 200 mg Lasmiditan 0.0 +/- 0.1; 50 mg Diphenhydramine 0.4 +/- 1.1 (p 0.6875)
• Total Number of Collisions (Secondary), Mean, collisions: Placebo 0.1 +/- 0.4; 100 mg Lasmiditan 0.0 +/- 0.1; 200 mg Lasmiditan 0.1 +/- 0.3; 50 mg Diphenhydramine 0.2 +/- 0.7 (p 0.1563)
• Total Number of Collisions (Secondary), Mean, collisions: Placebo 0.2 +/- 0.6; 100 mg Lasmiditan 0.0 +/- 0.2; 200 mg Lasmiditan 0.2 +/- 0.7; 50 mg Diphenhydramine 0.6 +/- 1.7 (p 0.1250)
• Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan (Secondary), Geometric mean, nanograms per milliliter: 100 mg Lasmiditan 183 +/- 31; 200 mg Lasmiditan 366 +/- 30
• PK: Area Under the Concentration Versus Time Curve (AUC) of Lasmiditan to the Last Timepoint (0-tlast) (Secondary), Geometric mean, ng*hour per milliliter: 100 mg Lasmiditan 1060 +/- 28; 200 mg Lasmiditan 2230 +/- 25

Adverse events

Time frame: up to 4 months

Other adverse events by term

• Study Protocol (PDF, 2018-02-21)
• Statistical Analysis Plan (PDF, 2018-05-22)

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company