A Study of Lasmiditan on Simulated Driving Performance in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03459612
• Collaborator: (none)
• Enrollment: 68
• Locations: 3
• Arms: 4
• Actual Duration (Months): 2.9
• Patients Per Site: 22.7
• Patients Per Site Per Month: 7.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Lasmiditan; Drug: Placebo; Drug: Diphenhydramine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Mar 26, 2018
• Actual Primary Completion Date: Jun 23, 2018
• Actual Study Completion Date: Jun 23, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo administered orally in one of four study periods.	Drug: Placebo; Administered orally
Experimental: 100 milligrams (mg) Lasmiditan 100 mg lasmiditan administered orally in one of four study periods.	Drug: Lasmiditan; Administered orally; Other Names: LY573144
Experimental: 200 mg Lasmiditan 200 mg lasmiditan administered orally in one of four study periods.	Drug: Lasmiditan; Administered orally; Other Names: LY573144
Active Comparator: Diphenhydramine 50 mg diphenhydramine administered orally in one of four study periods.	Drug: Diphenhydramine; Administered orally

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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

1. 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.

2. 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.

3. 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.

4. 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

5. 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.

6. 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.

7. 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).

8. 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).

9. 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).

10. 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

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Inc	Daytona Beach	Florida	United States	32117
2	Covance	Dallas	Texas	United States	75247-4989
3	Covance Clinical Research Inc	Madison	Wisconsin	United States	53704

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Feb 21, 2018
• Statistical Analysis Plan - May 22, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03459612
• Other Study ID Numbers: 17048; H8H-MC-LAIF
• First Posted: Mar 9, 2018
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diphenhydramine; Promethazine; Lasmiditan

Study Results

Participant Flow

Pre-assignment Detail	Randomized, 4-period cross-over study in healthy participants.

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4
Arm/Group Description	Period 1: Placebo administered PO. Period 2: 100 mg lasmiditan administered PO. Period 3: 50 mg diphenhydramine administered PO. Period 4: 200 mg lasmiditan administered PO. Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Period 1: 100 mg lasmiditan administered PO. Period 2: 200 mg lasmiditan administered PO. Period 3: Placebo administered PO. Period 4: 50 mg diphenhydramine administered PO. Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Period 1: 200 mg lasmiditan administered PO Period 2 : 50 mg diphenhydramine administered PO Period 3: 100 mg lasmiditan administered PO Period 4: Placebo administered PO Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Period 1: 50 mg diphenhydramine administered PO Period 2: Placebo administered PO Period 3: 200 mg lasmiditan administered PO Period 4: 100 mg lasmiditan administered PO Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration
Period Title: Period 1
STARTED	17	17	17	17
Received at Least 1 Dose of Study Drug	17	17	17	17
COMPLETED	17	17	17	17
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	17	17	17	17
Received at Least 1 Dose of Study Drug	17	17	17	17
COMPLETED	17	17	17	17
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	17	17	17	17
Received at Least 1 Dose of Study Drug	17	17	17	17
COMPLETED	17	17	17	17
NOT COMPLETED	0	0	0	0
Period Title: Period 1
STARTED	17	17	16	17
Received at Least 1 Dose of Study Drug	17	17	16	17
COMPLETED	17	17	16	17
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Total
Arm/Group Description	Participants received Placebo, 100 mg lasmiditan, 200 mg lasmiditan, 50 mg diphenhydramine as per below sequence. Period 1: Placebo administered PO. Period 2: 100 mg lasmiditan administered PO. Period 3: 50 mg diphenhydramine administered PO. Period 4: 200 mg lasmiditan administered PO. Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Participants received Placebo, 100 mg lasmiditan, 200 mg lasmiditan, 50 mg diphenhydramine as per below sequence. Period 1: 100 mg lasmiditan administered PO. Period 2: 200 mg lasmiditan administered PO. Period 3: Placebo administered PO. Period 4: 50 mg diphenhydramine administered PO. Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Participants received Placebo, 100 mg lasmiditan, 200 mg lasmiditan, 50 mg diphenhydramine as per below sequence. Period 1: 200 mg lasmiditan administered PO Period 2 : 50 mg diphenhydramine administered PO Period 3: 100 mg lasmiditan administered PO Period 4: Placebo administered PO Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Participants received Placebo, 100 mg lasmiditan, 200 mg lasmiditan, 50 mg diphenhydramine as per below sequence. Period 1: 50 mg diphenhydramine administered PO Period 2: Placebo administered PO Period 3: 200 mg lasmiditan administered PO Period 4: 100 mg lasmiditan administered PO Study treatments were administered at up to 4 dosing occasions (0, 6, and 10 hours on Day 1 and 22 hours on Day 2) within each period: lasmiditan was only administered at 0 hours. Each period is 3 days duration	Total of all reporting groups
Overall Participants	17	17	17	17	68
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	17 100%	17 100%	17 100%	17 100%	68 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 41.2%	5 29.4%	6 35.3%	10 58.8%	28 41.2%
Male	10 58.8%	12 70.6%	11 64.7%	7 41.2%	40 58.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 23.5%	1 5.9%	6 35.3%	1 5.9%	12 17.6%
Not Hispanic or Latino	13 76.5%	16 94.1%	11 64.7%	16 94.1%	56 82.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 5.9%	2 11.8%	1 5.9%	1 5.9%	5 7.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 41.2%	5 29.4%	3 17.6%	4 23.5%	19 27.9%
White	9 52.9%	9 52.9%	11 64.7%	12 70.6%	41 60.3%
More than one race	0 0%	1 5.9%	2 11.8%	0 0%	3 4.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	17 100%	17 100%	17 100%	17 100%	68 100%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	8 hours postdose in each dosing period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Least Squares Mean (Full Range) [centimeters]	29.85	30.83	31.61	34.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in Least Square (LS) means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; -0.43 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 0.32 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Means
	Estimated Value	4.98
	Confidence Interval	(2-Sided) 95%; 3.58 to 6.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	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)
Description	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.
Time Frame	12 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	67	68	68
Least Squares Mean (Full Range) [centimeters]	30.41	30.29	30.09	34.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -1.28 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.51 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	4.31
	Confidence Interval	(2-Sided) 95%; 3.17 to 5.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	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)
Description	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.
Time Frame	24 hours post dose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Least Squares Mean (Full Range) [centimeters]	32.04	31.07	31.00	36.10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Differnce in LS Means
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -2.30 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95%; -2.40 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority p-value tests null hypothesis that difference in LS means ≥ 4.4 versus alternative hypothesis that difference in LS means < 4.4.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	4.05
	Confidence Interval	(2-Sided) 95%; 2.73 to 5.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Karolinska Sleepiness Scale (KSS) Score
Description	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.
Time Frame	8 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participant that received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Mean (Standard Deviation) [Units on a scale]	3.19 (1.61)	3.46 (1.65)	3.90 (1.78)	3.93 (1.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Differences of Least Square Mean
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.22 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Karolinska Sleepiness Scale (KSS) Score
Description	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.
Time Frame	12 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	67	68
Mean (Standard Deviation) [units on a scale]	3.43 (1.57)	3.94 (1.62)	3.79 (1.74)	4.74 (2.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Differnce of Least Square Means
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Karolinska Sleepiness Scale (KSS) Score
Description	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.
Time Frame	24 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants that received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	67
Mean (Standard Deviation) [units on a scale]	4.19 (2.02)	3.72 (1.69)	3.93 (2.13)	4.75 (2.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -1.10 to -0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test
Description	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
Time Frame	8 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participant that received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	67	67	68
Mean (Standard Deviation) [Correct responses]	69.48 (11.32)	69.76 (10.17)	68.88 (11.27)	69.01 (11.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -1.61 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Lease Square Means
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -2.49 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -2.32 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test
Description	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.
Time Frame	12 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug and have evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Mean (Standard Deviation) [Correct responses]	71.33 (11.26)	70.91 (9.87)	72.16 (9.91)	68.21 (10.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95%; -3.52 to -0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -2.00 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-3.81
	Confidence Interval	(2-Sided) 95%; -5.53 to -2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test
Description	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.
Time Frame	24 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug and have evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Mean (Standard Deviation) [Correct responses]	70.78 (9.84)	70.53 (10.52)	70.66 (10.24)	68.31 (10.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -1.71 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -1.71 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of Least Square Means
	Estimated Value	-2.70
	Confidence Interval	(2-Sided) 95%; -4.13 to -1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Total Number of Collisions
Description	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).
Time Frame	8 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Mean (Standard Deviation) [collisions]	0.1 (0.2)	0.0 (0.2)	0.0 (0.1)	0.4 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6875
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.30
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3750
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.27
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0115
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.00
	Estimation Comments

11. Secondary Outcome

Title	Total Number of Collisions
Description	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).
Time Frame	12 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	67	68	68
Mean (Standard Deviation) [collisions]	0.1 (0.4)	0.0 (0.1)	0.1 (0.3)	0.2 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1563
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.42
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5938
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.44
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0938
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.54
	Estimation Comments

12. Secondary Outcome

Title	Total Number of Collisions
Description	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).
Time Frame	24 hours postdose in each dose period

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable data.

Arm/Group Title	Placebo	100 mg Lasmiditan	200 mg Lasmiditan	50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally (PO) in one of four study periods.	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.	Diphenhydramine administered PO in one of four study periods.
Measure Participants	67	68	68	68
Mean (Standard Deviation) [collisions]	0.2 (0.6)	0.0 (0.2)	0.2 (0.7)	0.6 (1.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1250
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.56
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 mg Lasmiditan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9590
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.94
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg Diphenhydramine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	Wilcoxon Signed Rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.76
	Estimation Comments

13. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan
Description	PK: Cmax of Lasmiditan
Time Frame	Day 1: Predose, 0.5 hour (hr), 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr, 10 hr, 12hr, 24hr, 36hr, 48hr postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	100 mg Lasmiditan	200 mg Lasmiditan
Arm/Group Description	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.
Measure Participants	68	67
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	183 (31)	366 (30)

14. Secondary Outcome

Title	PK: Area Under the Concentration Versus Time Curve (AUC) of Lasmiditan to the Last Timepoint (0-tlast)
Description	PK: AUC of Lasmiditan until the last time a concentration is detected.
Time Frame	Day 1: Predose, 0.5 hour (hr), 1hr, 1.5hr, 2hr, 3hr, 4hr, 6hr, 8hr, 10 hr, 12hr, 24hr, 36hr, 48hr postdose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	100 mg Lasmiditan	200 mg Lasmiditan
Arm/Group Description	100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.	200 mg Lasmiditan administered PO in one of four study periods.
Measure Participants	67	67
Geometric Mean (Geometric Coefficient of Variation) [ng*hour per milliliter]	1060 (28)	2230 (25)

Adverse Events

Time Frame	up to 4 months
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug.
Arm/Group Title	Placebo		100 mg Lasmiditan		200 mg Lasmiditan		50 mg Diphenhydramine
Arm/Group Description	Placebo administered orally in one of four study periods.		100 milligrams (mg) Lasmiditan administered orally (PO) in one of four study periods.		200 mg Lasmiditan administered PO in one of four study periods.		Diphenhydramine administered PO in one of four study periods.
All Cause Mortality
	Placebo		100 mg Lasmiditan		200 mg Lasmiditan		50 mg Diphenhydramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/68 (0%)		0/68 (0%)		0/68 (0%)
Serious Adverse Events
	Placebo		100 mg Lasmiditan		200 mg Lasmiditan		50 mg Diphenhydramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/68 (0%)		0/68 (0%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		100 mg Lasmiditan		200 mg Lasmiditan		50 mg Diphenhydramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/67 (9%)		23/68 (33.8%)		25/68 (36.8%)		7/68 (10.3%)
Gastrointestinal disorders
Nausea	4/67 (6%)	4	2/68 (2.9%)	2	2/68 (2.9%)	2	1/68 (1.5%)	1
General disorders
Fatigue	1/67 (1.5%)	1	6/68 (8.8%)	7	4/68 (5.9%)	4	1/68 (1.5%)	1
Nervous system disorders
Dizziness	1/67 (1.5%)	1	11/68 (16.2%)	11	12/68 (17.6%)	12	1/68 (1.5%)	1
Headache	0/67 (0%)	0	3/68 (4.4%)	3	6/68 (8.8%)	6	1/68 (1.5%)	1
Paraesthesia	1/67 (1.5%)	1	4/68 (5.9%)	4	6/68 (8.8%)	6	0/68 (0%)	0
Somnolence	0/67 (0%)	0	5/68 (7.4%)	6	7/68 (10.3%)	7	4/68 (5.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.