Conditions: Migraine
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 90
Healthy volunteers: yes

Brief summary:
This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design with 5-period (full) crossover study with participants randomized to treatment sequences. Participants will complete all 5 Periods.

During each Period, participants will come to the clinical research unit (CRU) and remain overnight before being dosed with a single dose of either lasmiditan, alprazolam, or placebo in the morning. Cognitive testing and driving simulation will be conducted post dosing. Participants will have a washout of at least 5 days between each Period.

This study is designed to test non-inferiority of lasmiditan doses relative to placebo, with an alprazolam test versus placebo to confirm the sensitivity of the simulator to detect treatment effects.

Detailed description:

Arms:
arm 1: Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. arm 2: Participants received 100mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. arm 3: Participants received 200mg of Lasmiditan tablets given as single doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. arm 4: Participants received 1mg of Alprazolam tablets as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning. arm 5: Participants received placebo tablets identical to Lasmiditan, administered as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Interventions: intervention 1: Lasmiditan intervention 2: Alprazolam intervention 3: Placebo
Intervention descriptions: intervention 1: Dose is based on treatment sequence in 5-way crossover intervention 2: Active comparator based on treatment sequence in 5-way crossover intervention 3: Placebo comparator based on treatment sequence in 5-way crossover

Protocol document:
Prot_001.pdf: 
Protocol H8H-CD-LAHG (COL MIG-106) 
 
 
A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, Cross-Over Study Assessing 
the Effects of Lasmiditan on Simulated Driving Performance in Normal Healthy Volunteers 
 
 
NCT03012334 
 
 
Approval Date: 06-Dec-2016 
 


 
  
CLINICAL TRIAL PROTOCOL: COL MIG-106 
Title: 
A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, 
Cross-Over Study Assessing the Effects of Lasmiditan on Simulated 
Driving Performance in Normal Healthy Volunteers 
Substance Identifier 
Lasmiditan 
IND number 
103,420 
Protocol Number 
COL MIG-106 
Algorithme Pharma Number (CUD-P8-917) 
Sponsor 
CoLucid Pharmaceuticals, Inc. 
222 Third Street, Suite 1320 
Cambridge, MA 02142 USA 
Principal 
Investigator 
 
 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone: 
 
Date of Protocol 
6 December 2016 
Sponsor 
Representative 
222 Third Street, sute 1320 
Cambridge, MA 02142 
Phone: 
 
Amendment # 
NA 
 
Confidentiality Statement 
The present protocol is property of CoLucid Pharmaceuticals, Inc. and it may not in full or in 
part-be passed on, reproduced, published or otherwise employed without the express permission 
of CoLucid Pharmaceuticals, Inc.. 
 
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Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 4 of 55 
2 
 SYNOPSIS 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
Study Title: 
A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, Cross-Over Study 
Assessing the Effects of Lasmiditan on Simulated Driving Performance in Normal Healthy 
Volunteers 
Study Number: COL MIG-106 
Study Phase: 
Phase 1  
Primary Objective: 
 To determine the effects of acute doses of lasmiditan 50 mg, 100 mg  and 200 mg 
compared to placebo and positive control (alprazolam 1.0 mg) on simulated driving 
performance in healthy subjects as measured by standard deviation of lateral position 
(SDLP) using the Cognitive Research Corporation Driving Simulator-MiniSim 
(CRCDS-MiniSim).   
Secondary Objective: 
 To determine the effects of lasmiditan 50 mg, 100 mg, and 200 mg compared to placebo 
and positive control (alprazolam 1.0 mg) on other measures of simulated driving 
performance (e.g., speed deviation, lane exceedance and other measures of lane position 
and speed control, cornering, collisions, and divided attention [DA]), CogScreen Symbol 
Digit Coding (SDC) test, and self-report measures (i.e., Karolinska Sleepiness Scale 
(KSS), Visual Analog Scales (VAS) addressing motivation and performance, and if the 
subject feels safe to drive). 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
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Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
Endpoints: 
Primary Endpoint:  
 SDLP 
Secondary Endpoints: 
 Sleepiness Endpoint - KSS 
 Self-reported readiness to drive (“Right now do you feel safe to drive?) 
 VAS to assess subject’s motivation and self-appraisal of their driving performance 
 Performance Endpoints 
 CogScreen SDC test 
o CogScreen SDC test 
o Number of correct responses  
o Response Accuracy 
o Standard deviation of reaction time 
 Driving Performance Endpoints 
 Lane exceedance; including number, maximum, duration, and area of exceedance 
 Ratio above speed limit, excessive speed count, excessive speed ratio 
 Average speed, speed deviation, speed count, speedings ratio 
 Excessive Ay (cornering speed threshold exceeded) 
 Collision count, off-road crashes, total collisions 
 DA: Correct Responses, Omission Errors, Commission Errors, Reaction Time, Standard 
Deviation of Reaction Times 
 Single-dose plasma drug levels and driving performance  
Study Design: 
This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design 
with 5-period (full) crossover study with subjects randomized to treatment sequences.  Subjects 
will complete all 5 Periods within the treatment sequence that they are randomized to. 
Treatments: 
 Treatment A:  Lasmiditan 50 mg 
 Treatment B:  Lasmiditan 100 mg 
 Treatment C:  Lasmiditan 200 mg  
 Treatment D:  Alprazolam 1 mg 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 6 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
 Treatment E:  Placebo 
Subjects will be randomized equally into one of ten treatment sequences: 
Treatment 
Sequence 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
1 
A 
B 
E 
C 
D 
2 
B  
C 
A 
D 
E 
3 
C 
D 
B 
E 
A 
4 
D 
E 
C 
A 
B 
5 
E 
A 
D 
B 
C 
6 
D 
C 
E 
B 
A 
7 
E 
D 
A 
C 
B 
8 
A 
E 
B 
D 
C 
9 
B 
A 
C 
E 
D 
10 
C 
B 
D 
A 
E 
 
Each Period will be approximately 5 days in duration (5-7 days). 
Study drug will be administered by site staff on Day 1 of each Period. Subjects will wear a 
blindfold when taking each dose to maintain the blind. The tablet size and shape are deemed 
similar enough to maintain the blind with a blindfolded subject. 
Testing is conducted 1.5 hours post-dose (on Days 1, 7, 14, 21, and 28 of each Period). 
Schematic of Design: 
Period 1  →   Washout 1  →    Period 2  →   Washout 2   →  Period 3 →   Washout 3   →  Period 4 →   Washout 4   →  Period 5  →  EOS 
Day 1 
          Days 2-6           Day 7 
        Days 8-13         Day 14 
    Days 15-20         Day 21          Days 22-27       Day 28        Day 35 
 
A sufficient number of subjects will be enrolled to complete 80 healthy volunteers in the 5-
period crossover study.  The washout between Periods will be at least 5 days.  Subjects will be 
evaluated following a single dose.  
The positive control (alprazolam 1.0 mg) is included to establish the sensitivity of the study 
endpoints to detecting residual sedation. 
Screening (Visit 1) will include procedures as described in the Schedule of Activities and further 
in the protocol.  Prior to randomization, subjects will be screened for simulator sickness and will 
receive standardized training on the driving simulator and cognitive test battery.  Screening 
procedures and screening assessments may be performed on different days but must be 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 7 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
completed within 28 days before Period 1 (Visit 2).  The Familiarization and Practice drives on 
the driving simulator must be completed no more than 21 days prior to Period 1. 
Treatments within each Period  
Subjects will return to the site where, according to the randomization schedule, they will be 
assigned and dosed with study medication (lasmiditan, alprazolam or placebo). 
Prior to dosing (the evening of clinical research unit [CRU] admission) they will complete a 
20-minute practice drive on the CRCDS-MiniSim and a practice trial on the CogScreen SDC 
test. 
Within approximately 85 minutes of dosing, subjects will perform the CogScreen SDC Test, 
KSS, and indicate their self-perceived safety to drive.  Subjects will then perform the Country 
Vigilance-Divided Attention (CVDA) driving scenario on the CRCDS-MiniSim commencing 
approximately 90 minutes (1.5 hours) post-dosing. Upon completion of the driving scenario 
subjects will be administered a VAS to assess subject’s motivation and self-appraisal of their 
driving performance. 
Subjects will leave the clinical site at approximately 24-hour post-dose. Blood draws for 
pharmacokinetics will be taken during the Periods predose and approximately 155 minutes (-15 
to +30 minutes) post-dose.   
The total duration of subject participation will be approximately 5 weeks (range 5-7 weeks). 
Subject Population: 
Inclusion Criteria: 
1. Able and willing to voluntarily consent to participate in this study and provide written 
informed consent prior to start of any study-specific procedures.  
2. Males and females between the ages of 21 and 50 years of age (inclusive).  No more 
than 60% of one gender will be enrolled on the study.    
3. Body Mass Index (BMI) between 18 and 32 kg/m2 (inclusive). 
4. Subject is able to reliably perform study assessments (SDLP no higher than 1 standard 
deviation greater than the mean for normal healthy adults completing the practice 
scenario; SDC Correct no less than 1 standard deviation below the mean for healthy 
adults in their age range); demonstrates the ability to understand task instructions, and 
is physically capable (e.g., adequate manual dexterity, vision, and hearing) and 
cognitively capable of performing study tasks. 
5. Subject possesses a valid driver’s license and is an active driver.  Drives a minimum 
of 10,000 miles (about 16,000 km) per year for the previous 3 years. 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 8 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
6. Subject must also demonstrate simulator sickness questionnaire scores which are not 
indicative of simulator sickness as defined in the driving simulation operations 
manual.  
7. Subject has a regular sleep pattern, are not engaged in shift-work, and in general,  have 
at least 7 hours of sleep each night (bedtime occurs between 21:00 and 24:00 hours). 
8. Subject has a score < 10 on the Epworth Sleepiness Scale. 
9. Use of a medically highly effective form of birth control during the study and for 
thirty (30) days: 
a. A female volunteer must meet one of the following criteria: 
i. If of childbearing potential – agrees to use one of the accepted 
contraceptive regimens from at least 28 days prior to the drug 
administration, during the study and for at least 60 days after the dose. 
An acceptable method of contraception includes one of the following: 
ii. Abstinence from heterosexual intercourse 
iii. Systemic contraceptives (birth control pills, 
injectable/implant/insertable hormonal birth control products, 
transdermal patch) 
iv. Intrauterine device (with or without hormones) 
v. Condom with spermicide or condom with intra-vaginally applied 
spermicide 
vi. If of non-childbearing potential – should be surgically sterile (i.e. has 
undergone complete hysterectomy, bilateral oophorectomy, or tubal 
ligation) or in a menopausal state (at least one year without menses) 
b. A male volunteer with sexual partners who are pregnant, possibly pregnant, or 
who could become pregnant must meet the following criteria: 
i. Participant is unable to procreate, defined as surgically sterile (i.e. has 
undergone a vasectomy within at least the last 6 months) 
ii. Participant is apt to procreate and agrees to use one of the accepted 
contraceptive regimens from first drug administration until 3 months 
after the drug administration. An acceptable method of contraception 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 9 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
includes one of the following: 
iii. Abstinence from heterosexual intercourse. 
iv. Condom with spermicide or condom with intra-vaginally applied 
spermicide 
c. A male volunteer agrees to refrain from sperm donation from drug 
administration until 3 months after the drug administration. 
10. Subjects who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures. 
Exclusion Criteria: 
1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, 
hematological, gastrointestinal, endocrine, immunologic, neurological, oncologic, or 
psychiatric disease or any other condition that, in the opinion of the Investigator, 
would jeopardize the safety of the subject or the validity of the study results. 
2. A history within 2 years of, 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. 
3. A history of  difficulty in falling asleep or staying asleep in the previous 3 months, that 
is considered clinically significant by the investigator. 
4. Subject has a history or diagnosis of any of the following conditions: 
a. Primary or secondary insomnia 
b. Narcolepsy 
c. Cataplexy (familial or idiopathic) 
d. Circadian Rhythm Sleep Disorder 
e. Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking 
disorder, and rapid eye movement behavior disorder 
f. Sleep-related Breathing Disorder (obstructive or central sleep apnea syndrome, 
central alveolar hypoventilation syndrome) 
g. Periodic Limb Movement Disorder 
h. Restless Legs Syndrome 
i. Primary Hypersomnia 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 10 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
j. Excessive Daytime Sleepiness (EDS) 
k. Subject has visual or auditory impairment which in the opinion of the 
investigator would interfere with study related procedures or study conduct. 
5. Expected to use any other medication or dietary supplement to promote sleep 
including over-the-counter sleep medications, during their participation in the study. 
6. Subject consumes excessive amounts of coffee, tea, cola, or other caffeinated 
beverages per day.  Excessive amount is defined as greater than 6 servings (1 serving 
is approximately equivalent to 120 mg of caffeine) 
7. Subject has traveled across 1 or more time zones (transmeridian travel) in the last 2 
weeks prior to randomization or is expected to travel across 1 or more time zones 
during the study. 
8. Expected to work on a rotating shift during their participation in the study. 
9. Subject works a night shift. 
10. History or presence of seizure disorder.  
11. History of urinary retention, angle closure glaucoma, or increased ocular pressure. 
12. History of gastrointestinal tract surgery, except appendectomy.  
13. Has abnormal finding on the physical exam, medical history, electrocardiogram 
(ECG), or clinical laboratory results at Screening, that are considered clinically 
significant by the investigator.  
14. Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 
msec, QRS >110 msec and QTc > 440 msec) on the screening ECG or other clinically 
significant ECG abnormalities 
15. History of orthostatic hypotension, fainting spells, or blackouts, that are considered 
clinically significant by the investigator.  
16. The presence of chronic or acute infections, that are considered clinically significant 
by the investigator.  
17. History of allergy/hypersensitivity (including drug allergies) that are deemed relevant 
to the study as judged by the Investigator.  
18. Use of psychoactive prescription or non-prescription medications, psychoactive 
nutritional supplements or herbal preparations within 2 weeks or 5 half-lives 
(whichever is longer) of admission to the CRU on Day 1.  
19. Has received any previous study drug within 30 days prior to the first dose of this 
study drug.  


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 11 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
20. Is a smoker of more than 10 cigarettes or eCigarettes, or 3 cigars or 3 pipes per day, 
and is unable to refrain from smoking while confined to the CRU.  
21. Has any history of dependency or treatment for substance abuse within the past 
2 years.  
22. Subject with a history of alcoholism or who consumes excessive amounts of alcohol, 
defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately 
equivalent to: beer [284 mL/9 ounces], wine [125 mL/4 ounces], or distilled spirits 
[25 mL/1 ounce]) per day.   
23. Subjects who consume alcohol on a regular basis (i.e., ≥ 5 times/week) before bedtime 
will be excluded from the study. 
24. Inability to comply with the dietary regimen of the clinical research center.  
25. Pregnancy / positive pregnancy test.  
26. Planning to become pregnant during the study or within 30 days of study completion.  
27. Inability to use adequate contraception (as defined in item 9 of the Inclusion Criteria) 
during the study. It is recommended that adequate contraception be used for 1 month 
following completion of the study.   
28. Has a positive screen for alcohol or other drugs of abuse (amphetamines, 
methamphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates). 
29. Has a history for Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) 
at Screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV.  
Planned Number of Subjects:  
A sufficient number of subjects will be enrolled to ensure completion of 80 subjects. 
Test Product; Dose; and Mode of Administration: 
Lasmiditan 50, 100, and 200 mg tablets and alprazolam 1.0 mg tablets will be provided for the 
study by the Sponsor.  
The subjects will be instructed to swallow the tablets whole, with approximately 240 mL of 
water.  Study drug will be administered by qualified unblinded CRU personnel and a mouth 
check performed. 
Duration of Treatment: 
The total duration of study participation will be approximately 5 weeks (5-7 weeks). 
Safety Assessments: 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 12 of 55 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
Adverse Events: 
Adverse events (AEs) will be captured from the time of obtaining informed consent until 
discharge from the study. 
Pregnancy Test: 
A serum pregnancy test will be done at screening and end of study for females of child-bearing 
potential.  A serum pregnancy test will also be collected at each CRU check-in for females of 
child-bearing potential.  A positive pregnancy test at any time during the study will automatically 
disqualify the subject from further participation in the trial. 
Serum Chemistries, Hematology and Urinalysis: 
Blood will be collected for serum chemistries and hematology and urine will be collected for 
urinalysis at the following visits: 
 Screening,  
 Day 35 or end of study (EOS).  
Vital Signs: 
Vital signs (blood pressure and heart rate) will be collected at the following visits/time points: 
 Screening,  
 Day -1, 6, 13, 20, and 27 upon clinic check-in, 
 Day 1, 7, 14, 21, and 28 prior to dosing and at 70 minutes (prior to CogScreen testing) 
post morning dose.  
Temperature will be measured at Screening and Day 35 or End of Study. 
Electrocardiogram 
Twelve-lead ECG recording will be collected at Screening and Day 35 or EOS prior to 
discharge. 
Pharmacokinetic (PK) Blood Sampling: 
Lasmiditan: 
Blood samples for the determination of plasma lasmiditan concentrations will be drawn at the 
following time points following each lasmiditan or placebo dose: 
 Days 1, 7, 14, 21, and 28 pre-dose 
 Days 1, 7, 14, 21, and 28 at 155 minutes (-15 to +30 minutes) post-dose 
Statistical Plan and Methods:  


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
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Sponsor: 
CoLucid Pharmaceuticals, Inc. 
Name of Finished Product: 
Lasmiditan 
Name of Active Ingredient: 
Lasmiditan 
Safety: 
Safety analysis will be based on all subjects enrolled who receive at least 1 dose of the study 
medication. The safety analysis will evaluate adverse events and additional safety parameters.  
The number and percentage of subjects experiencing at least one AE will be summarized by 
body system, preferred term, and treatment.  If appropriate, AEs will also be summarized by 
intensity and relationship to study drug.  SAEs, if any, will be tabulated. 
Additional safety parameters will be assessed from summaries of physical examinations, 12-lead 
ECGs and vital signs.  The 12-lead ECG results will be categorized as normal, clinically 
significant abnormal, and not clinically significant abnormal.  Hematology, chemistry and 
urinalysis laboratory test results will be categorized relative to the normal ranges. The changes 
from baseline for each of these parameters at post-dose time points will be presented.  Complete 
listings and summary tables for all safety information including AEs, laboratory safety data, 
ECG, vital signs and physical examination will be included in the study report. 
Pharmacokinetics: 
The decision as to which plasma samples collected will be assayed for evaluation of 
pharmacokinetics/pharmacodynamics will be determined by CoLucid Pharmaceutical, Inc.  The 
relationship between single-dose and steady-state plasma drug levels and driving performance 
will be evaluated, data permitting. If indicated, these samples may also be assayed and/or pooled 
for assay in an exploratory manner for metabolites and/or additional pharmacodynamic markers.  
Pharmacodynamics: 
The primary end point, SDLP, will be analyzed using a mixed model with fixed effects for 
sequence, period, and treatment, and a random effect for subject within sequence.   
Secondary endpoints will be evaluated similarly, however Lane Exceedance will be log 
transformed (more specifically 1n(x+1)) prior to analyses.  Pair-wise comparisons for readiness 
to drive will be analyzed using McNemar test. 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
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3 
TABLE OF CONTENTS 
1 
SIGNATURES ........................................................................................................................2 
1.1 
Sponsor’s Representative .......................................................................................................... 2 
1.2 
Investigator ................................................................................................................................ 3 
2 
SYNOPSIS ..............................................................................................................................4 
3 
TABLE OF CONTENTS ......................................................................................................14 
4 
ABBREVIATIONS AND DEFINITIONS OF TERMS ......................................................17 
5 
STUDY ADMINISTRATION SCHEDULE ........................................................................19 
5.1 
Principal Investigator .............................................................................................................. 19 
5.2 
Study Director ......................................................................................................................... 19 
5.3 
Medical Monitor ...................................................................................................................... 19 
5.4 
SAE Reporting Contact Information - Sponsor ....................................................................... 19 
6 
BACKGROUND AND RATIONALE FOR THE STUDY .................................................20 
6.1 
Introduction ............................................................................................................................. 20 
6.2 
Drug Profile ............................................................................................................................. 20 
6.2.1 
Lasmiditan ............................................................................................................... 20 
6.2.2 
Alprazolam .............................................................................................................. 20 
6.3 
Rationale .................................................................................................................................. 21 
6.3.1 
Study design ............................................................................................................ 21 
6.3.2 
Lasmiditan Dose Level ........................................................................................... 21 
6.3.3 
Positive Control Dose Level ................................................................................... 21 
7 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................22 
7.1 
Primary Objective.................................................................................................................... 22 
7.2 
Secondary Objectives .............................................................................................................. 22 
7.3 
Primary Endpoint .................................................................................................................... 22 
7.4 
Secondary Endpoints ............................................................................................................... 22 
8 
SUBJECT DEFINITION ......................................................................................................24 
8.1 
Inclusion Criteria ..................................................................................................................... 24 
8.2 
Exclusion Criteria .................................................................................................................... 25 
9 
STUDY DESIGN..................................................................................................................28 
9.1 
Summary of Study Design ...................................................................................................... 28 
9.2 
Meals ....................................................................................................................................... 29 
9.3 
Subject Assignment ................................................................................................................. 29 
10 
DAILY STUDY ACTIVITIES .............................................................................................30 
10.1 Screening ................................................................................................................................. 30 
10.2 Study Periods ........................................................................................................................... 30 
10.2.1 
CRU Admission Days (Visits 2, 5, 8, 11, and 14: Days -1, 6, 13, 20, and 27) ....... 30 
10.2.2 
Dosing Days (Visits 3, 6, 9, 12, and 15: Days 1, 7, 14, 21, and 28) ....................... 31 
10.3 Estimated Daily Schedule ....................................................................................................... 31 
10.4 Day 35±2 (Follow-up) ............................................................................................................. 32 


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11 
STUDY PROCEDURES ......................................................................................................33 
11.1 CVDA Driving Scenario on the CRCDS-MiniSim ................................................................. 33 
11.2 Karolinska Sleepiness Scale .................................................................................................... 33 
11.3 Self-perceived Safety to Drive Question ................................................................................. 33 
11.4 Digit Symbol Substitution Test (CogScreen Symbol Digit Coding) ....................................... 34 
11.5 Visual Analog Scale (VAS) to Assess Subject’s Motivation and Self-Appraisal ................... 34 
11.6 Vital Signs ............................................................................................................................... 34 
11.7 Clinical Laboratory Assessments ............................................................................................ 34 
11.8 Blood Collection for Lasmiditan Plasma Concentrations ....................................................... 35 
11.8.1 
Sample Storage and Shipment ................................................................................ 36 
11.9 Blood Collection Volume for the Study .................................................................................. 36 
11.10 Medical and Social History ..................................................................................................... 36 
11.11 Physical Examination .............................................................................................................. 36 
11.12 Columbia-Suicide Severity Rating Scale ................................................................................ 36 
11.13 Pregnancy Test ........................................................................................................................ 36 
11.14 Study Drug Preparation and Dispensing ................................................................................. 37 
11.15 Study Drug Administration ..................................................................................................... 37 
11.16 Concurrent Medication ............................................................................................................ 38 
11.17 Fluid, Food, and Lifestyle Restrictions ................................................................................... 38 
11.18 Discontinuation Criteria and Procedures ................................................................................. 38 
11.18.1 
Premature Termination of Study/Closure of Study Sites ........................................ 39 
12 
EVALUATION AND REPORTING OF ADVERSE EVENTS..........................................40 
12.1 Adverse Event Definitions ...................................................................................................... 40 
12.1.1 
Severity Assessment ............................................................................................... 40 
12.1.2 
Causality Assessment .............................................................................................. 41 
12.2 Routine Reporting ................................................................................................................... 41 
12.3 Serious Adverse Event Reporting ........................................................................................... 42 
13 
STATISTICAL METHODS .................................................................................................43 
13.1 Determination of Sample Size ................................................................................................. 43 
13.2 Analysis Populations ............................................................................................................... 44 
13.3 Statistical Analysis – General Considerations ......................................................................... 44 
13.4 Safety Analysis ........................................................................................................................ 44 
13.4.1 
Adverse Events ....................................................................................................... 45 
13.4.2 
Clinical Laboratory ................................................................................................. 45 
13.4.3 
Vital Signs ............................................................................................................... 45 
13.4.4 
Twelve-lead ECG .................................................................................................... 45 
13.4.5 
Physical Examination .............................................................................................. 45 
13.5 Pharmacokinetic Analysis ....................................................................................................... 46 
13.6 Pharmacodynamic Analyses .................................................................................................... 46 
14 
CLINICAL SUPPLIES .........................................................................................................47 
14.1 Product Description ................................................................................................................. 47 


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14.2 Storage Requirements .............................................................................................................. 47 
14.3 Accountability ......................................................................................................................... 47 
15 
BIOLOGICAL SPECIMENS ...............................................................................................48 
16 
CLINICAL AND LABORATORY DATA COLLECTION ................................................48 
16.1 Case Report Forms .................................................................................................................. 48 
16.2 Laboratory Results .................................................................................................................. 48 
17 
STUDY DOCUMENTATION .............................................................................................49 
17.1 Source Documents ................................................................................................................... 49 
17.2 Access to Records ................................................................................................................... 49 
17.3 Retention of Records ............................................................................................................... 49 
18 
INSTITUTIONAL REVIEW BOARD (IRB) ......................................................................49 
19 
ETHICAL CONDUCT OF THE STUDY ............................................................................50 
20 
INFORMED CONSENT ......................................................................................................50 
21 
CONFIDENTIALITY...........................................................................................................50 
21.1 Confidentiality of Data ............................................................................................................ 50 
21.2 Confidentiality of Subject Records ......................................................................................... 50 
22 
COMPLIANCE WITH LAW, AUDIT, AND DEBARMENT ............................................51 
23 
QUALITY CONTROL AND QUALITY ASSURANCE ....................................................52 
24 
PUBLICATIONS ..................................................................................................................52 
25 
REFERENCES .....................................................................................................................53 
26 
SCHEDULE OF ACTIVITIES.............................................................................................54 
 
 


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4 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
5-HT 
5-Hydroxytryptamine 
z 
Apparent terminal rate constant determined from the slope of the log 
transformed plasma concentration curve 
AE(s) 
Adverse event(s)                     
AUC0- 
Area under the plasma concentration vs. time curve from time 0 to infinity, 
calculated as AUC = AUC0–t + AUCextra. AUCextra represents an 
extrapolated value obtained by C /λz, where C is the observed concentration at 
time t at or above LOQ, and λz is the estimated apparent terminal rate constant 
AUC0-t 
Area under the plasma concentration vs. time curve from time 0 to the time t of 
the last quantifiable concentration, calculated by means of the mixed log-linear 
trapezoidal rule 
BMI 
Body mass index 
cm 
Centimeter 
Cmax 
Maximum plasma concentration as observed 
CNS 
Central Nervous System 
CRA 
Clinical research associate 
CRCDS-MiniSim 
Cognitive Research Corporation Driving Simulator-MiniSim 
CRO 
Contract research organization 
CRU 
Clinical research unit 
CS 
Clinically significant 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CVDA 
Country Vigilance-Divided Attention 
DA 
Divided attention 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDS 
Excessive daytime sleepiness 
EOS 
End of study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization  
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
kg/m2 
Kilogram per meter squared 


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km 
Kilometer 
KSS 
Karolinska Sleepiness Scale 
LC 
Liquid chromatography 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mL 
Milliliter  
NI 
Non-inferiority 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SDC 
Symbol digit coding 
SDLP 
Standard deviation of lateral position 
SOPs 
Standard operating procedures 
TEAE 
Treatment Emergent Adverse Event 
t1/2 
Apparent terminal elimination half-life, calculated as ln(2)/λz 
Tmax 
Time to maximum plasma concentration 
VAS 
Visual analog scale 
WHO 
World Health Organization 
 


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5 
 STUDY ADMINISTRATION SCHEDULE 
5.1 
Principal Investigator 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone:
 
5.2 
Study Director 
200 Central Avenue, Suite 1230 
Saint Petersburg, FL 33701 
Office:  
 
Mobile:  
 
5.3 
Medical Monitor 
Algorithme Pharma  
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone: 
 
 
5.4 
SAE Reporting Contact Information - Sponsor 
Serious adverse events (SAEs) should be reported to the Medical Monitor at Algorithme Pharma 
within 24 hours after Investigator or Investigator’s representative becomes aware of their 
occurrence. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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6 
BACKGROUND AND RATIONALE FOR THE STUDY 
6.1 
Introduction 
Migraine is a common neurological disorder and was ranked by the World Health Organization 
(WHO) in its 2010 Global Burden of Disease survey as one of 7 most debilitating conditions, 
and as the third most common disease in the world among both males and females [1].  CoLucid 
Pharmaceuticals, Inc. is developing lasmiditan (COL-144), which is intended for the acute 
treatment of migraine patients with and without aura and will be orally administered.  Lasmiditan 
is a small molecule 5-HT(5-Hydroxytryptamine)1F receptor agonist with the chemical name of 
2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)pyridine-2-yl]benzamide hemisuccinate.  
Triptans, which are 5-HT1B/1D receptor agonists, are well established as an acute therapy for 
migraine, though they are not effective in all patients or attacks. Triptans were developed as 
cerebral vasoconstrictors, mediated via their affinity for 5-HT1B receptors located on vascular 
smooth muscle. Inherent in this mechanism of action is a liability for coronary vasoconstriction, 
and therefore, triptans are contraindicated in patients with cardiovascular disease. 
Unlike triptans, lasmiditan is a highly selective and potent agonist at the 5-HT1F receptor with 
>470-fold higher affinity for the 5-HT1F receptor than for 5-HT1B/1D receptors. In preclinical 
models (rodent) of relevance to migraine, agonists selective for 5-HT1F receptors inhibited 
trigeminal nociceptive processing without affecting blood vessel tone [2-4]. Unlike triptans, 
lasmiditan did not constrict rabbit saphenous vein [2], an assay predictive of human coronary 
artery constriction [5]. Lasmiditan is under development as a neurally acting treatment for 
migraine without the vasoconstrictor liability of triptans. 
The most frequently reported adverse events identified in the lasmiditan clinical development 
program are CNS in nature based on the mechanism of action of the drug.  The most common 
reported AEs are dizziness and fatigue, therefore a driving study evaluating the impact of 
lasmiditan on driving performance will be conducted.  
6.2 
Drug Profile 
6.2.1 Lasmiditan 
Full details of lasmiditan pre-clinical and clinical safety and tolerability data are contained in the 
Investigator's Brochure. 
6.2.2 Alprazolam  
Full details of alprazolam pre-clinical and clinical safety and tolerability data are contained in the 
Package Insert.   


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6.3 
Rationale  
6.3.1 Study design 
This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design 
with 5-period (full) crossover study with subjects randomized to treatment sequences.  Subjects 
will complete all 5 Periods. 
During each Period, subjects will come to the clinical research unit (CRU) and remain overnight 
before being dosed with a single dose of either lasmiditan, alprazolam, or placebo in the 
morning. Cognitive testing and driving simulation will be conducted approximately 1.25 hours 
and 1.5 hours post dosing, respectively. Subjects will have a washout of at least 5 days between 
each Period.   
6.3.2 Lasmiditan Dose Level 
Lasmiditan 50 mg, 100 mg, and 200 mg will be given as single doses on Day 1, 7, 14, 21, or 28 
(dependent upon the assigned treatment sequence) in the morning.  
6.3.3 Positive Control Dose Level 
Alprazolam1.0 mg will be given as a single dose on Day 1, 7, 14, 21, or 28 (dependent upon the 
assigned treatment sequence) in the morning and will serve as the positive control. 


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7 
STUDY OBJECTIVES AND ENDPOINTS 
7.1 
Primary Objective 
The primary objective of this study is to determine the effects of acute doses of lasmiditan 50 
mg, 100 mg  and 200 mg compared to placebo and positive control (alprazolam 1.0 mg) on 
simulated driving performance in healthy subjects as measured by standard deviation of lateral 
position (SDLP) using the Cognitive Research Corporation Driving Simulator-MiniSim 
(CRCDS-MiniSim).   
7.2 
Secondary Objectives 
The secondary objectives of this study  are to determine the effects of lasmiditan 50 mg, 100 mg, 
and 200 mg compared to placebo and positive control (alprazolam 1.0 mg) on other measures of 
simulated driving performance (e.g., speed deviation, lane exceedance and other measures of 
lane position and speed control, cornering, collisions, and divided attention [DA]), CogScreen 
Symbol Digit Coding (SDC) test, and self-report measures (i.e., Karolinska Sleepiness Scale 
(KSS), Visual Analog Scales addressing motivation and performance, and if the subject feels 
safe to drive).  
7.3 
Primary Endpoint 
The primary endpoint for this study is simulated driving performance as measured by SDLP 
using the CRCDS-MiniSim. 
7.4 
Secondary Endpoints 
The secondary endpoints for this study include other measures of simulated driving performance, 
KSS and CogScreen SDC test. 
 Sleepiness Endpoint - KSS 
 Self-reported readiness to drive (“Right now do you feel safe to drive?) 
 Visual Analog Scales (VAS) to assess subject’s motivation and self-appraisal of their driving 
performance 
 Performance Endpoints 
 CogScreen SDC test 
o CogScreen SDC test 
o Number of correct responses  
o Response Accuracy 
o Standard deviation of reaction time 
 Driving Performance Endpoints 
 Lane exceedance; including number, maximum, duration, and area of exceedance 
 Ratio above speed limit, excessive speed count, excessive speed ratio 
 Average speed, speed deviation, speed count, speedings ratio 


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 Excessive Ay (cornering speed threshold exceeded) 
 Collision count, off-road crashes, total collisions 
 DA: Correct Responses, Omission Errors, Commission Errors, Reaction Time, Standard 
Deviation of Reaction Times 
 Single-dose plasma drug levels and driving performance 


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8 
SUBJECT DEFINITION 
Individuals are eligible for this study if they meet all inclusion and no exclusion criteria. The 
criteria below will be assessed at the Screening visit. Continued eligibility will be assessed by 
serum pregnancy and screens for alcohol and drugs of abuse on Days -1, 6, 13, 20, and 27. 
8.1 
Inclusion Criteria 
1. Able and willing to voluntarily consent to participate in this study and provide written 
informed consent prior to start of any study-specific procedures.  
2. Males and females between the ages of 21 and 50 years of age (inclusive).  No more than 
60% of one gender will be enrolled in the study.    
3. Body Mass Index (BMI) between 18 and 32 kg/m2 (inclusive). 
4. Subject is able to reliably perform study assessments (SDLP no higher than 1 standard 
deviation greater than the mean for normal healthy adults completing the practice scenario; 
SDC Correct no less than 1 standard deviation below the mean forhealthy adults in their age 
range); demonstrates the ability to understand task instructions, and is physically capable 
(e.g., adequate manual dexterity, vision, and hearing) and cognitively capable of performing 
study tasks. 
5. Subject possesses a valid driver’s license and is an active driver.  Drives a minimum of 
10,000 miles (about 16,000 km) per year for the previous 3 years. 
6. Subject must also demonstrate simulator sickness questionnaire scores which are not 
indicative of simulator sickness as defined in the driving simulation operations manual.  
7. Subject has a regular sleep pattern, are not engaged in shift-work, and in general, have at 
least 7 hours of sleep each night (bedtime occurs between 21:00 and 24:00 hours). 
8. Subject has a score < 10 on the Epworth Sleepiness Scale. 
9. Use of a medically highly effective form of birth control during the study and for thirty (30) 
days: 
a. A female volunteer must meet one of the following criteria: 
i. If of childbearing potential – agrees to use one of the accepted contraceptive regimens 
from at least 28 days prior to the drug administration, during the study and for at least 
60 days after the dose. An acceptable method of contraception includes one of the 
following: 
ii. Abstinence from heterosexual intercourse 
iii. Systemic contraceptives (birth control pills, injectable/implant/insertable hormonal 
birth control products, transdermal patch) 


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iv. Intrauterine device (with or without hormones) 
v. Condom with spermicide or condom with intra-vaginally applied spermicide 
vi. If of non-childbearing potential – should be surgically sterile (i.e. has undergone 
complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal 
state (at least one year without menses) 
b. A male volunteer with sexual partners who are pregnant, possibly pregnant, or who could 
become pregnant must meet the following criteria: 
i. Participant is unable to procreate, defined as surgically sterile (i.e. has undergone a 
vasectomy within at least the last 6 months) 
ii. Participant is apt to procreate and agrees to use one of the accepted contraceptive 
regimens from first drug administration until 3 months after the drug administration. 
An acceptable method of contraception includes one of the following: 
iii. Abstinence from heterosexual intercourse. 
iv. Condom with spermicide or condom with intra-vaginally applied spermicide 
c. A male volunteer agrees to refrain from sperm donation from drug administration until 3 
months after the drug administration. 
10. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory 
tests, and other study procedures.  
8.2 
Exclusion Criteria 
1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, 
hematological, gastrointestinal, endocrine, immunologic, neurological, oncologic, or 
psychiatric disease or any other condition that, in the opinion of the Investigator, would 
jeopardize the safety of the subject or the validity of the study results. 
2. A history within 2 years of, 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. 
3. A history of difficulty either falling asleep or staying asleep in the previous 3 months, that is 
considered clinically significant by the investigator. 
4. Subject has a history or diagnosis of any of the following conditions: 
a. Primary or secondary insomnia 
b. Narcolepsy 
c. Cataplexy (familial or idiopathic) 


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d. Circadian Rhythm Sleep Disorder 
e. Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, 
and rapid eye movement behavior disorder 
f. Sleep-related Breathing Disorder (obstructive or central sleep apnea syndrome, central 
alveolar hypoventilation syndrome) 
g. Periodic Limb Movement Disorder 
h. Restless Legs Syndrome 
i. Primary Hypersomnia 
j. Excessive Daytime Sleepiness (EDS) 
k. Subject has visual or auditory impairment which in the opinion of the investigator would 
interfere with study related procedures or study conduct. 
5. Expected to use any other medication or dietary supplement to promote sleep including over-
the-counter sleep medications, during their participation in the study. 
6. Subject consumes excessive amounts of coffee, tea, cola, or other caffeinated beverages per 
day.  Excessive amount is defined as greater than 6 servings (1 serving is approximately 
equivalent to 120 mg of caffeine) 
7. Subject has traveled across 1 or more time zones (transmeridian travel) in the last 2 weeks 
prior to randomization or is expected to travel across 1 or more time zones during the study. 
8. Expected to work on a rotating shift during their participation in the study. 
9. Subject works a night shift. 
10. History or presence of seizure disorder.  
11. History of urinary retention, angle closure glaucoma, or increased ocular pressure. 
12. History of gastrointestinal tract surgery, except for appendectomy.  
13. Has abnormal finding on the physical exam, medical history, electrocardiogram (ECG), or 
clinical laboratory results at Screening, that are considered clinically significant by the 
investigator.  
14. Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 msec, 
QRS >110 msec and QTc > 440 msec) on the screening ECG or other clinically significant 
ECG abnormalities 
15. History of orthostatic hypotension, fainting spells, or blackouts, that are considered clinically 
significant by the investigator.  
16. The presence of chronic or acute infections, that are considered clinically significant by the 
investigator.  


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17. History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the 
study as judged by the Investigator.  
18. Use of psychoactive prescription or non-prescription medications, psychoactive nutritional 
supplements or herbal preparations within 2 weeks or 5 half-lives (whichever is longer) of 
admission to the CRU on Day -1.  
19. Has received any previous study drug within 30 days prior to the first dose of this study drug.  
20. Is a smoker of more than 10 cigarettes or eCigarettes, or 3 cigars or 3 pipes per day, and is 
unable to refrain from smoking while confined to the CRU.  
21. Has any history of dependency or treatment for substance abuse within the past 2 years.  
22. Subject with a history of alcoholism or who consumes excessive amounts of alcohol, defined 
as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer 
[284 mL/9 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day. 
23. Subjects who consume alcohol on a regular basis (i.e., ≥ 5 times/week) before bedtime will 
be excluded from the study. 
24. Inability to comply with the dietary regimen of the clinical research center.  
25. Pregnancy / positive pregnancy test. 
26. Planning to become pregnant during the study or within 1 month of study completion.  
27. Inability to use adequate contraception (as defined in item 9 of the Inclusion Criteria) during 
the study. It is recommended that adequate contraception be used for 30 days following 
completion of the study.   
28. Has a positive screen for alcohol or other drugs of abuse (amphetamines, methamphetamines, 
barbiturates, benzodiazepines, cocaine, cannabinoids, opiates). 
29. Has a history for Hepatitis B, Hepatitis C , or Human Immunodeficiency Virus (HIV) at 
Screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV. 


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9 
STUDY DESIGN 
9.1 
Summary of Study Design 
This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design 
with 5-period (full) crossover study with subjects randomized to treatment sequences.  Subjects 
will complete all 5 Periods within the treatment sequence that they are randomized to. 
Treatments: 
 Treatment A:  Lasmiditan 50 mg 
 Treatment B:  Lasmiditan 100 mg 
 Treatment C:  Lasmiditan 200 mg  
 Treatment D:  Alprazolam 1 mg 
 Treatment E:  Placebo 
Subjects will be randomized equally into one of ten treatment sequences: 
Treatment 
Sequence 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
1 
A 
B 
E 
C 
D 
2 
B  
C 
A 
D 
E 
3 
C 
D 
B 
E 
A 
4 
D 
E 
C 
A 
B 
5 
E 
A 
D 
B 
C 
6 
D 
C 
E 
B 
A 
7 
E 
D 
A 
C 
B 
8 
A 
E 
B 
D 
C 
9 
B 
A 
C 
E 
D 
10 
C 
B 
D 
A 
E 
 
Each Period will be approximately 5 days in duration (5-7 days). 
Study drug will be administered by site staff on Day 1 of each Period. Subjects will wear a 
blindfold when taking each dose to maintain the blind. The tablet size and shape are deemed 
similar enough to maintain the blind with a blindfolded subject. 
Testing is conducted 1.5 hours post-dose (on Days 1, 7, 14, 21, and 28). 
Schematic of Design: 
Period 1  →   Washout 1  →    Period 2  →   Washout 2   →  Period 3 →   Washout 3   →  Period 4 →   Washout 4   →  Period 5   →   EOS 
Day 1 
          Days 2-6            Day 7         Days 8-13         Day 14 
    Days 15-20         Day 21          Days 22-27       Day 28          Day 35 
 


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A sufficient number of subjects will be enrolled to complete 80 healthy volunteers in the 5-
period crossover study.  The washout between Periods will be at least 5 days and not more than 
14 days.  Subjects will be evaluated following a single dose.  
The positive control (alprazolam 1.0 mg) is included to establish the sensitivity of the study 
endpoints to detecting residual sedation. 
The total duration of subject participation will be approximately 5 weeks (range 5-7 weeks). 
9.2 
Meals 
During each confinement period, subjects will consume only food and beverages that are 
provided to them by the CRU staff. Standard meals (e.g. breakfast, dinner, and evening snack) 
will be provided to the subjects while confined to the CRU. On the morning of testing, subjects 
will be provided a low fat breakfast. The breakfast menu will include non-caffeinated breakfast 
foods and beverages: e.g., cereal, fruit, pastry, microwavable breakfast sandwiches, and juices.  
The breakfast menu will be standardized such that menu items will be the same at each study 
visit and at each study site.  Breakfast will be provided after the morning dose. 
9.3 
Subject Assignment 
Prior to dosing, subjects will be randomly assigned to one of ten treatment sequences and dosed 
with study medication (lasmiditan, alprazolam or placebo) based upon a randomization scheme 
provided by Algorithme Pharma. Only the qualified person(nel) assigned to prepare and 
administer the study treatment will have access to the randomization schedule and dispensing 
records during the study period. 


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6 December 2016 
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10 
DAILY STUDY ACTIVITIES 
A complete Schedule of Events can be found in Section 26. 
10.1 
Screening 
Screening (Visit 1) will include procedures as described in the Schedule of Activities and further 
in the protocol.  Prior to randomization, subjects will be screened for simulator sickness and will 
receive standardized training on the driving simulator and cognitive test battery.  Screening 
procedures and screening assessments may be performed on different days but must be 
completed within 28 days before Period 1 (Visit 2).  The Familiarization and Practice drives on 
the driving simulator must be completed no more than 21 days prior to Period 1. 
In addition, each potential study participant will have the following assessments done by the 
Investigator or designee within 28 days prior to study start: medical and social history and 
demographic data, including sex, age, race, ethnicity, body weight (kg), height (cm), 
BMI (kg/m2), and smoking habits. Each potential participant will receive a physical examination, 
vital signs (including blood pressure, heart rate, and temperature), ECG, Epworth Sleepiness 
Scale, and the laboratory tests for hematologic, hepatic, and renal function. Urine drug and 
alcohol screen tests will be conducted on all potential subjects. Serum pregnancy tests will be 
conducted on all female subjects. The Columbia-Suicide Severity Rating Scale (C-SSRS) will 
also be administered. 
Only medically healthy subjects with clinically acceptable laboratory profiles and ECGs will be 
enrolled in the study. The informed consent documents will be discussed with each potential 
participant, and each individual will sign an informed consent document for the study prior to 
any study-specific procedures being performed. 
A positive test result for pregnancy, urine drug or alcohol screen will end the screening process. 
10.2 
Study Periods  
10.2.1 CRU Admission Days (Visits 2, 5, 8, 11, and 14: Days -1, 6, 13, 20, and 27) 
Within 28 days after the Screening visit, eligible subjects will return for Period 1 (Visit 2).  
Subjects who meet the inclusion and no exclusion criteria will be instructed to return to the clinic 
on Day -1.  
 A serum pregnancy test will be performed for all females of child-bearing potential upon 
admission to the unit.  
 Continued subject eligibility will be verified, including serum pregnancy and screens for 
alcohol and drugs of abuse. 
 The alcohol and drug screens will be repeated. 
 A practice drive (approximately 20 minutes) will be performed on the driving simulator.  
 A practice trial on the CogScreen SDC test. 


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 Vital signs will be measured. 
 C-SSRS 
 Any concurrent medication use will be recorded. 
 Adverse Events (AEs) will be assessed. 
Subjects will spend the night at the CRU.   
10.2.2 Dosing Days (Visits 3, 6, 9, 12, and 15: Days 1, 7, 14, 21, and 28) 
After a period of 8.5 hours in bed, subjects will be awakened. According to the 
randomization schedule, subjects will be assigned and dosed with study medication 
(lasmiditann, alprazolam, or placebo). 
  The following procedures will be performed: 
 Pre-dose vital signs will be taken. 
 A pre-dose pharmacokinetic (PK) blood sample will be taken (within 30 minutes before 
dosing). 
 Subject will receive the study drug dose. 
 Vital signs will be measured pre-dose and at 1.17 hours after dosing. 
Approximately 1.25 hours after dosing, subjects will perform the CogScreen SDC Test and KSS, 
and indicate their self-perceived safety to drive.   
Subjects will then perform the Country Vigilance-Divided Attention (CVDA) driving scenario 
on the CRCDS-MiniSim commencing approximately 1.5 hours post-dosing. Upon completion of 
the driving scenario subjects will be administered a VAS to assess subject’s motivation and self-
appraisal of their driving performance. The following procedures will also be performed:  
 A post-dose PK blood sample will be taken approximately 155 minutes (-15 to +30 
minutes) post-dose.  
 AEs will be recorded.  
 Any concurrent medication use will be recorded. 
Subjects will leave the clinical site at approximately 24-hour post-dose. However, they will be 
advised to stay at the clinical site, if judged necessary by the physician in charge, for safety reasons. 
10.3 
Estimated Daily Schedule 
Following is a schedule of events from dosing through the study testing that will be followed for 
all Periods: 


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Procedure 
Clock Time* 
Hours Post-Dose 
BEDTIME/AWAKENING 
23:00/07:30 
0 
Vitals  
8:00 
0 
PK Draw 
8:15 
0 
Dosing 
8:30 
0 
Breakfast 
9:00 
0.5 
Vitals 
9:40 
1.17 
CogScreen 
9:45 
1.25 
KSS 
9:55 
1.42 
Self-perceived safety to drive 
9:55 
1.42 
CRCDS 
10:00 
1.5 
VAS of Motivation and Driving Performance 
11:05 
2.58 
PK Draw 
11:05 
2.58 
The VAS should be completed upon termination of the drive. 
*Actual times may vary based on dosing time (e.g., if dosing begins between at 8:00 and 8:30 
and is slightly staggered for each subject, all times would then change relative to the actual 
dosing time of the individual subject). 
10.4 
Day 35±2 (Follow-up) 
The following procedures will be performed 5 to 9 days after Study Day 28 dosing during the 
Follow-up visit: 
 Body weight will be obtained. 
 Vital signs including temperature will be measured.  
 Physical Exam 
 C-SSRS will be obtained 
 Twelve-lead ECG recording will be collected  
 Blood samples for chemistry and hematology will be drawn. 
 Urine samples will be collected for urinalysis. 
 Blood samples for pregnancy testing will be collected. 
 AEs will be recorded.  
 Any concurrent medication use will be recorded.  
If an AE has not resolved, an additional Follow-up visit or visits may be scheduled until the 
event resolves or is deemed to be an indefinitely continuing event. At the Investigator’s 
discretion, minor AEs may be followed until resolution via telephone contact. All SAEs must be 
followed for at least 30 days after the last dose of study drug. During the added follow-up 
visit(s), any tests indicated based on clinical signs or symptoms may be performed to aid in the 
evaluation of AEs.  


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11 
STUDY PROCEDURES 
11.1 
CVDA Driving Scenario on the CRCDS-MiniSim 
The present study employs the CVDA driving scenario, a 62.1 mile (100 km), monotonous, two-
lane highway driving task that includes a secondary visual vigilance task (DA).  The monotonous 
Country Vigilance scenario has been demonstrated to be sensitive to detect the effects of fatigue 
or sleepiness on driving performance [6].  This scenario has been useful in measuring the effects 
of sleep deprivation, Obstructive Sleep Apnea, chronic primary insomnia, and is sensitive to 
central nervous system (CNS) depressants (e.g., alcohol and sedating antihistamines).  Results 
obtained using this methodology are comparable to those obtained using over-the-road driving 
tests [7]. 
Subjects will perform the driving simulator test at the times specified in Section 10.  Data will be 
captured in electronic format.  Details are provided in the Cognitive Research Corporation 
CRCDS Testing Operations Manual. 
11.2 
Karolinska Sleepiness Scale 
The KSS [8] will be used to assess subjective level of sleepiness.  This is a subject self-report 
measure of situational sleepiness and provides an assessment of alertness/sleepiness at a 
particular point in time.  The KSS has been found to correlate with electroencephalogram and 
behavioral variables [9].   It is a 9-point categorical Likert scale: 
(1) “extremely alert” 
(2) 
(3) “alert 
(4) 
(5) “neither sleepy nor alert” 
(6) 
(7) “sleepy” 
(8) 
(9) “extremely sleepy-fighting sleep”    
Subjects will self-report their KSS assessments at the times specified in Section 10.  The 
subject’s self-reported scores will be recorded in the electronic case report form (eCRF). 
11.3 
Self-perceived Safety to Drive Question 
Prior to driving the subject will be asked a simple question as to whether they feel safe to drive 
(“Right now do you feel safe to drive?”).  Subject will answer “yes” or “no”.  The answer will be 
recorded in the eCRF. 


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11.4 
Digit Symbol Substitution Test (CogScreen Symbol Digit Coding) 
Symbol Digit Coding (SDC) will be used in this study to measure attention, visual scanning, 
working memory, and speed of information processing.  Symbol Digit Coding is a computer 
analogue of the conventional symbol-substitution task found in the WAIS-R Digit Symbol 
subtest and the Symbol Digit Modalities Test [10].  
The Symbol Digit Coding test will be administered by trained study site personnel.  Subjects will 
perform the test prior to the driving simulation test at the times specified in Section 10.  The 
subject will perform the test by interacting with an electronic monitor screen.  Data will be 
captured in electronic format.  Details are provided in the CogScreen® Examiner Manual, 
CogScreen LLC, 2016.   
11.5 
Visual Analog Scale (VAS) to Assess Subject’s Motivation and Self-Appraisal 
After completing the driving simulation, subjects will assess their own performance and their 
level of motivation to perform at their best during the driving simulation. 
Subjects will respond to 2 questions: 
1. How well you think you drove for the last 60 minutes? 
2. How motivated did you feel to drive at your best during the last 60 minutes of driving? 
Subjects will record their response to each question by writing a vertical line on a 100 mm 
horizontal, linear visual analog scale indicating their level of performance (Not Satisfactory to 
Satisfactory) and motivation (Not Motivated to Motivated).  Scores on the 100 mm linear scale 
will be measured to the nearest millimeter from the left.  The subject’s scores will be recorded in 
the eCRF.   
11.6 
Vital Signs 
Vital signs will include the measurement of blood pressure (systolic and diastolic) using an 
appropriately sized cuff after subjects have rested in a seated position for a minimum of 5 
minutes. Heart rate will also be measured. Temperature in degrees centigrade will be measured 
only at Screening and end of study (EOS). 
11.7 
Clinical Laboratory Assessments 
A certified laboratory will be used to perform all routine hematology, clinical chemistry, and 
urinalysis. Planned laboratory analyses include:  


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Category 
Test Name  
Hematology 
Hemoglobin 
Hematocrit 
Platelets 
Prothrombin Time (PT)c 
Red blood cells 
White blood cells with differential (absolute) 
Chemistry 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Alkaline phosphatase 
Blood urea nitrogen (BUN) 
Creatinine 
Gamma glutamyltransferase (GGT) 
Glucose 
Potassium 
Sodium 
Total and direct bilirubin 
Urinalysis 
Bilirubin 
Erythrocytes 
Glucose 
Ketones 
Leukocytes 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Other 
Urine drug and alcohol screena,b 
Serum Pregnancyd 
a Screening and check-in each Period (Days -1, 6, 13, 20, and 27). 
b  Includes testing for amphetamines, methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 
ethanol and opiates – ethanol may be determined by Breathalyzer. 
c  Screening only. 
d  Serum pregnancy at Screening, Days -1, 6, 13, 20, and 27, and Day 35/EOS. 
Note: The complete panel of safety labs (other than where footnoted) will be completed at Screening and 
Follow-up/Day 35 (or EOS).  Other tests may be performed as deemed necessary by the investigator. 
11.8 
Blood Collection for Lasmiditan Plasma Concentrations  
Within Periods (Days 1, 7, 14, 21, and 28), blood sampling will be performed prior to dosing 
(within 30 minutes prior to dose) and approximately 155 minutes (-15 to +30 minutes) after 
dosing for plasma determination of lasmiditan.  Documentation stating the exact time of blood 
sampling in relation to the actual time of dosing for each subject by subject number, will be 
included with each shipment of plasma samples. 
Blood samples will be collected into heparinized polypropylene tubes (~5.0 mL).  The tubes 
should be mixed immediately after filling by gently inverting the tubes at least 8 to 10 times.  
Thereafter, the tubes will be centrifuged as soon as possible (within 30 minutes of collection) at a 
minimum of 1500 g for 15 minutes until cells and plasma are well separated.  The resulting 
plasma samples will be transferred into two (duplicate) 2 ml cryovial tubes and labeled 
appropriately. 


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Plasma samples will be analyzed for lasmiditan at Covance Laboratories, Inc. Madison 
Wisconsin, using a validated liquid chromatography with tandem mass spectrometric detection 
(LC/MS/MS) method (limit of quantification (LOQ): 1 ng/mL). A detailed method description, 
including validation, calibration and quality assurance procedures will be included in the 
bioanalytical report which will be part of the Final Study Report. 
11.8.1 Sample Storage and Shipment 
The samples will be frozen as soon as possible (within 24 hours) of collection and stored frozen 
at –20°C until time of shipment to Covance Laboratories, Inc., 3301 Kinsman Blvd. Madison, 
WI 53704, USA for analysis.  All samples will be shipped frozen with sufficient dry ice to 
maintain frozen conditions for at least 72 hours at times arranged between the study site and the 
analytical laboratory. The times of blood sample collection, pipetting and freezing will be 
recorded in the source documents. 
11.9 
Blood Collection Volume for the Study 
For Periods 1-5, a total of approximately 50 mL (10 x 5 mL samples) will be collected from each 
subject for PK analysis. In addition, up to 48 mL of blood will be collected for screening and 
end-of-study clinical laboratory evaluations.  
11.10 Medical and Social History 
A medical and social history will be performed at Screening. Each subject’s history of alcohol 
and drug use will be evaluated. Subject’s caffeine consumption and tobacco use will be 
evaluated to ensure that the protocol will be followed during the course of the study. Continued 
eligibility will be evaluated on Day -1 and adherence to protocol restrictions will be confirmed 
throughout the study.  
11.11 Physical Examination 
A physical examination will be performed at Screening and Day 35 or EOS.  
11.12 Columbia-Suicide Severity Rating Scale  
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a suicidal ideation rating scale. The 
scale identifies behaviors and thoughts that are associated with an increased risk of suicidal 
actions in the future. The C-SSRS will be performed at Screening, on Days -1, 6, 13, 20, and 27, 
and Day 35 or EOS. 
11.13 Pregnancy Test 
A serum pregnancy test will be performed at Screening and Day 35 or EOS for all females of 
child-bearing potential.  A serum pregnancy test will also be collected at each CRU check-in 
visit for females of child-bearing potential.  A positive pregnancy test at any time during the 
study will immediately terminate the subject from further participation in the study.  


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11.14 Study Drug Preparation and Dispensing 
The Sponsor will supply study treatment in an unblinded fashion. To maintain the double-blind 
status of the study, the following dispensing and dosing procedures will be followed. The site 
will identify a qualified party and alternate(s) who will be responsible for dispensing and 
administering the study treatment. Aside from dispensing and administering the study treatment, 
the qualified party dispenser will not be otherwise involved in the study. Algorithme Pharma will 
provide randomization codes directly to the individual identified by the study site. The 
randomization codes will be kept in a secured area with access limited to only the assigned 
qualified party dispenser.  
The qualified party dispenser will prepare study treatment for each subject in a designated 
dispensing room. The qualified party dispenser will assign the next available randomization 
number and dispense the appropriate tablet into dispensing cups. The qualified party dispenser 
will complete the study treatment dispensing record. The study treatment dispensing record will 
remain in a secure locked area with access limited to the qualified party dispenser and the 
alternate(s). A second individual with no other study involvement will witness the preparation 
and dispensing process to confirm proper dispensation of study medication in accordance with 
the randomization schedule. No other study personnel will be present in the designated 
dispensing room at the time of study treatment dispensing.  
The qualified party dispenser will inform the study coordinator once the study treatment is 
dispensed and is ready to be administered to the subject. The qualified party dispenser will 
deliver the study treatment from the designated dispensing room to the subject’s room and will 
administer dosing 
Study treatment administration will be completed in the subject’s room. Study treatment will be 
dispensed in the morning, after a period of 8.5 hours in bed. 
All study medications will be administered orally with 240 mL of room temperature water. A 
mouth check will be performed by CRU personnel for each dose of study drug administered.   
11.15 Study Drug Administration 
To maintain the study blind for lasmiditan 50 mg, 100 mg and 200 mg, alprazolam 1 mg, and 
placebo, subjects will be blindfolded during dosing in each Period. Subjects will be given one 
tablet in the morning on the day of testing in the CRU. Dosing will be observed by a study staff 
member (qualified party dispenser); no other study personnel will be present at the time of 
dosing. 
The qualified party dispenser will place the tablet into a dispensing cup. The blindfolded subject 
will transfer the study treatment directly from the cup into their mouth. All study medications 
will be administered orally with 240 mL of room temperature water. The subjects will be 
instructed to swallow the study tablet whole, without chewing the tablet. Mouth and hand checks 
will be performed by CRU personnel for each dose of study drug administered. 


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11.16 Concurrent Medication 
 Subjects are to abstain from using psychoactive prescription or non-prescription 
medications, psychoactive nutritional supplements or herbal preparations within 2 weeks 
or 5 half-lives (whichever is longer) of Day 1.  
 Subjects are to abstain from using any other medication or dietary supplement to promote 
sleep, including over the counter sleep medications, during their participation in the study. 
 Subject will abstain from using antihistamine or any other drugs that can cause 
drowsiness, and will discuss any new prescription with the investigator.  
 No other medications (with the exception of birth control) are to be taken by the subjects 
without prior approval from the Principal Investigator and the Sponsor unless it is a 
medical emergency. All concomitant medication taken during the trial should be recorded 
with indication, daily dose, and start and stop dates of administration. 
11.17 Fluid, Food, and Lifestyle Restrictions 
 Subjects are not allowed to consume alcoholic beverages from 48 hours prior to admission 
to the CRU on Days -1, 6, 13, 20, and 27 until discharged from the CRU following 
completion of all procedures of each Period on Days 2, 8, 15, 22, and 29. At all other 
times alcohol consumption is limited to no more than 3 alcoholic beverages or equivalent 
(beer [284 mL], wine [125 mL], or distilled spirits [25 mL]) per day.  
 The subject will be cautioned regarding the operation of automobiles or other dangerous 
machinery, and activities made hazardous by decreased alertness. Patients should also be 
cautioned that the CNS effects of alprazolam may be additive to those of alcohol and other 
CNS depressants.  
 Subjects are not allowed to consume caffeine containing products from approximately 
1 pm on the days of admission to the CRU (Days -1, 6, 13, 20, and 27) until discharged 
from the CRU following completion of all procedures on Days 2, 8, 15, 22, and 29. At all 
other times, caffeinated beverages will be permitted to no more than 4 units per day 
amounts (1 unit = 120 mg caffeine). 
 Subjects are to refrain from vigorous physical activity from 24 hours prior to admission to 
the CRU on Days -1, 6, 13, 20, and 27 until discharged from the CRU following 
completions of all procedures on Days 2, 8, 15, 22, and 29. 
11.18 Discontinuation Criteria and Procedures 
According to the Declaration of Helsinki, all subjects have the right to withdraw from a study at 
any time, regardless of their reasons. In addition, it is the right of the Investigator to remove 
subjects from the study as a result of AEs, protocol violation, or any other reason. 


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11.18.1Premature Termination of Study/Closure of Study Sites 
The study may be terminated prematurely if new toxicological findings or results affecting the 
safety of the subjects become available. A site may be closed prematurely if recruitment is too 
slow, poor quality data is produced, or there is evidence of attempted or proven fraud. 
In the event the Sponsor prematurely terminates the study, the Investigator will promptly notify 
the Institutional Review Board (IRB). 


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12 
EVALUATION AND REPORTING OF ADVERSE EVENTS  
12.1 
Adverse Event Definitions 
An AE is defined as any untoward medical occurrence in a subject administered a medicinal 
product and which does not necessarily have to have a causal relationship with this treatment. 
AEs occurring after the initiation of the treatment are referred to as treatment emergent adverse 
events (TEAEs). An AE can therefore be any unfavorable and unintended sign (for example, an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to this medicinal product. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug 
caused the AE. ‘Reasonable possibility’ means there is evidence to suggest a causal relationship 
between the drug and the AE. A suspected adverse reaction implies a lesser degree of certainty 
about causality than adverse reaction, which means any AE caused by a drug. 
An AE may be: 
 A new illness, 
 Worsening of a concomitant illness, 
 An effect of the study medication including comparator; it could be an abnormal 
laboratory value as well as a significant shift from baseline within normal range which 
the Principal Investigator or medical qualified designate considers to be clinically 
important. 
Surgical procedures themselves are not AEs. They are therapeutic measures for conditions that 
required surgery. The condition for which the surgery is required is an AE, if it occurs or is 
detected during the study period. Planned surgical measures permitted by the clinical study 
protocol and the conditions(s) leading to these measures are not AEs, if the condition(s) was 
(were) known before the start of study treatment. In the latter case, the condition should be 
reported as medical history. 
A serious adverse event (SAE) or reaction is any untoward medical occurrence that at any dose: 
 Results in death, 
 Is life-threatening, 
 Requires inpatient hospitalization or prolongation of existing hospitalization, 
 Results in persistent or significant disability or incapacity (defined as a substantial 
disruption of a person’s ability to conduct normal life functions), 
 Is a congenital anomaly or birth defect, 
Is an important medical event (including development of drug dependence or drug abuse) that 
may jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed above (according to medical judgment of the Principal Investigator). 
12.1.1 Severity Assessment  
All AEs will be graded as mild, moderate, or severe according to the following definitions: 


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Mild: 
Causing no limitation of usual activities; the subject may experience slight 
discomfort. 
Moderate: 
Causing some limitation of usual activities; the subject may experience annoying 
discomfort. 
Severe: 
Causing inability to carry out usual activities; the subject may experience 
intolerable discomfort or pain. 
Every effort will be made to obtain an adequate evaluation of the severity. 
12.1.2 Causality Assessment  
The Principal Investigator or a medical qualified designate will determine the relationship of any 
AE to study drug using the following guidelines in Table 12-1. 
Table 12-1 Adverse Event Relationship to Study Drug 
Relationship to Drug 
Comment 
Reasonable Possibility 
A temporal relationship exists between the AE onset and 
administration of the investigational product that cannot be readily 
explained by the subject’s clinical state or concomitant therapies. 
Furthermore, the AE appears with some degree of certainty to be 
related, based on the known therapeutic and pharmacologic actions or 
AE profile of the investigational product. 
In case of cessation or reduction of the dose, the AE may abate or 
resolve and it may reappear upon rechallenge. 
No Reasonable Possibility 
Evidence exists that the AE has an etiology other than the 
investigational product. 
For SAEs, an alternative causality must be provided (eg, pre-existing 
condition, underlying disease, intercurrent illness, or concomitant 
medication). 
 
12.2 
Routine Reporting  
For the purposes of this study, the period of observation of AEs extends from the screening visit 
until the follow-up call. During this period, all AEs spontaneously reported by the subject, 
observed by the clinical staff, or elicited by general questioning will be recorded and reported in 
the CRF. 
Any AE which remains unresolved as of the last visit will require an evaluation and follow-up 
until the AE has been resolved or a reasonable explanation for its persistence found, or is deemed 
mild and safely resolving. 
In the case of AEs deemed related to the Investigational Product, every effort will be made to 
determine the final outcome. 
It is the Investigator’s responsibility to ensure subjects experiencing AE receive appropriate 
follow-up, treatment where required, and that every action is well documented. 


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Subjects will be questioned on their health status at the beginning of study period and before 
departure from the clinical site. Open-ended questions will be asked. 
Subjects will be questioned on their health status at the beginning of the study period and before 
the departure from the clinical site. Open-ended questions will be asked. 
Classification will be performed by System Organ Class (SOC) and Preferred Term (PT) using 
the Medical Dictionary for Regulatory Activities (MedDRA), version 19.0 or higher. 
In general, AEs occurring secondary to other events (eg, clinical sequelae or a cascade of events) 
should be identified by their primary cause. For example, if severe vomiting is known to result in 
dehydration, it is sufficient to record only vomiting as SAE or AE in the CRF. However, 
medically significant AEs occurring secondary to an initiating event that are separated in time 
should be recorded as independent events on the CRF. 
Pregnancy in a female subject on the study shall be reported to the sponsor within 24 hours of the 
knowledge of its occurrence by the Principal Investigator or designee (for pregnancies occurring 
during the course of the study or immediately following the end of the study). Because of the 
possibility that the fetus/embryo could have been exposed to the study drug through the parent 
and for the subject’s safety, the pregnancy will be followed up to determine its outcome, 
including spontaneous or voluntary termination, details of birth, presence or absence of any birth 
defects, congenital anomalies, or maternal and/or newborn complications. 
The pregnancy will be recorded and reported by the Principal Investigator or designee to the 
sponsor. Pregnancy follow-up will also be properly recorded to ensure quality and completeness 
of the data belonging to the study drug and will include an assessment of the possible causal 
relation between the study drug and any pregnancy outcome. Any SAE experienced during 
pregnancy will be reported on a SAE Report Form. 
12.3 
Serious Adverse Event Reporting  
Algorithme Pharma will notify any SAE to the sponsor, without regard to causality, within 
24 hours after becoming aware of its occurrence.  
If, during follow-up, any non-serious AE worsens and eventually meets the criteria for an SAE, 
that AE should be recorded as a new SAE. 
The initial SAE report must be as complete as possible, including details of the current illness 
and SAE, and an assessment of the causal relationship between the event and the investigational 
product(s). Information not available at the time of the initial report (eg, an end date for the AE, 
laboratory values received after the report, or hospital discharge summary) must be documented. 
All follow-up information must be reported as soon as the relevant info is available. 
The notification should be directed to the following sponsor representatives: 


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Tel. 
 
Fax. 
 
Email: 
 
An SAE will be considered “unexpected” if the AE is not listed in the investigator brochure or is 
not listed at the specificity or severity that has been observed; or, if an investigator brochure is 
not required or available, is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application. "Unexpected," as used in this 
definition, also refers to AEs that are mentioned in the investigator brochure as occurring with a 
class of drugs or as anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation. 
Algorithme Pharma will determine whether any serious unexpected related AE must be reported 
to the IRB. If so, the event will be reported via fax or email within 15 calendar days of the 
investigator or staff becoming aware of the event. 
The sponsor will determine whether the SAE must be reported in an expedited manner to the 
appropriate regulatory agencies. If so, Algorithme Pharma Inc, on the behalf of the sponsor will 
report the event to the appropriate regulatory agencies, and all participating investigators. 
During a clinical trial conducted in Canada, it is required to inform Health Canada of any 
serious, unexpected adverse drug reaction that has occurred inside or outside Canada: 
 Where it is neither fatal nor life-threatening, within 15 days after becoming aware of the 
information; 
 Where it is fatal or life-threatening, immediately where possible and, in any event, within 
7 days after becoming aware of the information; and 
 Within 8 days after having informed Health Canada of the ADR, submit as complete a 
report as possible which includes an assessment of the importance and implication of any 
findings. 
If reports of any new and unexpected AEs become available to the sponsor during the clinical 
portion of this study (related or not to the present study), the sponsor must advise 
Algorithme Pharma, through its Clinical Investigator, of those events. If required by the sponsor, 
Algorithme Pharma may advise the Canadian authorities. 
13 
STATISTICAL METHODS 
13.1 
Determination of Sample Size 
This study is designed to test non-inferiority of lasmiditan doses relative to placebo, with an 
alprazolam test versus placebo to confirm the sensitivity of the simulator to detect treatment 
effects.  The following assumptions were made in the sample size computation: (a) within-
subject standard deviation for SDLP is approximately 6 cm; (b) the true difference between 
lasmiditan doses and placebo is 0; and, (c) the non-inferiority (NI) margin is proposed to be 
PPD
PPD
PPD
PPD
PPD
PPD


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4.4 cm, which is the effect seen with 0.05% of BAC.  Under these assumptions, a sample of 
80 subjects would provide in excess of 90% power to establish non-inferiority of any given dose 
of lasmiditan compared to placebo in terms of the primary end point, SDLP.  This sample size is 
considered more than adequate to detect alprazolam differences from placebo, which are 
anticipated to exceed the NI margin. 
13.2 
Analysis Populations 
 PK Population – All subjects with evaluable PK data will be included in the 
pharmacokinetic population.  Subjects with incomplete PK data, e.g. data missing from 
one entire study Period, will be listed and the derived PK parameters will not be 
considered for summary statistics and analytical evaluations. 
 Intent-to-Treat (ITT) Population – The ITT Population includes all randomized and 
treated subjects.  This is the analysis population for efficacy analysis.  Subjects will (in 
general) be included in all analyses for which data are non-missing. 
 Safety Population – The Safety Population includes all subjects who are treated with 
study medication. 
13.3 
Statistical Analysis – General Considerations 
This section describes the general approaches planned to analyze the data from this study.  
Additional details of the planned analyses outlined here, will be further described in the 
Statistical Analysis Plan (SAP).   
To address multiplicity of testing, for the primary endpoint of SDLP, ascending doses of 
lasmiditan will be interpreted in a sequential manner, starting with the 50 mg dose and 
proceeding to 100 mg and then 200 mg.  Doses of lasmiditan will be considered non-inferior to 
placebo if the upper 95% confidence limit on the difference in SDLP between that dose and 
placebo is less than 4.4 cm and lower doses also do not exceed the NI margin.  No adjustment to 
alpha levels will be made for either the comparison of alprazolam to placebo or lasmitidan, or for 
secondary endpoints or analyses.  Formal statistical tests (where performed) will be two-sided 
and testing at the alpha=0.05 level of significance. 
In general, categorical variables will be summarized by the count (N) and percentage of subjects 
(%).  Continuous variables will be summarized by the number of non-missing observations (N), 
mean, standard deviation (SD), median, minimum, and maximum values. 
All study data are to be displayed in the data listings. 
13.4 
Safety Analysis 
Safety analysis will be based on all subjects enrolled who receive at least 1 dose of the study 
medication. The safety analysis will evaluate adverse events and additional safety parameters.  
The number and percentage of subjects experiencing at least one AE will be summarized by 


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body system, preferred term, and treatment.  If appropriate, AEs will also be summarized by 
intensity and relationship to study drug.  SAEs, if any, will be tabulated. 
Additional safety parameters will be assessed from summaries of physical examinations, 12-lead 
ECGs and vital signs.  The 12-lead ECG results will be categorized as normal, clinically 
significant abnormal, and not clinically significant abnormal.  Hematology, chemistry and 
urinalysis laboratory test results will be categorized relative to the normal ranges. The changes 
from baseline for each of these parameters at post-dose time points will be presented.  Complete 
listings and summary tables for all safety information including AEs, laboratory safety data, 
ECG, vital signs and physical examination will be included in the study report. 
13.4.1 Adverse Events 
Adverse events will be summarized by dose, Medical dictionary for medical activities 
(MedDRA) terminology (latest version), severity and relation to study drug.  The descriptive 
statistics presented for each system-organ class and preferred term will be the number of subjects 
with event (N), the percent of subjects exposed with event (%), and the number of events (E).  
All AEs will be listed by subject, including demographic information, dose, MedDRA latest 
version, system organ class, and preferred term. 
13.4.2 Clinical Laboratory 
Clinical laboratory values will be summarized by descriptive statistics by dose.  Changes from 
baseline in clinical laboratory values will be summarized by descriptive statistics.  All clinical 
laboratory values outside normal range (including Screening/Visit 1 and EoS/Visit 5 
examination) will be listed by dose and subject number, including demographic information and 
flagging of values. 
13.4.3 Vital Signs 
Vital signs (BP, HR and body temperature) will be summarized by dose using descriptive 
statistics.  Changes from baseline in vital signs will be summarized by descriptive statistics for 
each dose. 
13.4.4 Twelve-lead ECG 
All ECG endpoints will be listed by dose, subject and time of assessment and summarized by 
descriptive statistics.  Changes from baseline in ECG parameters will be summarized by 
descriptive statistics by dose. 
13.4.5 Physical Examination 
Subjects with any changes in the physical examination evaluation from Screening/Visit 1 to 
EOS/Day 35 will be listed.  A description of the study population in terms of baseline measures 
and demographics will be presented. 


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13.5 
Pharmacokinetic Analysis 
The decision as to which plasma samples collected will be assayed for evaluation of 
pharmacokinetics/pharmacodynamics will be determined by CoLucid Pharmaceuticals, Inc. The 
correlations between single-dose plasma drug concentrations the morning of the driving 
simulation and the primary and key secondary end points will be evaluated, data permitting. If 
indicated, these samples may also be assayed and/or pooled for assay in an exploratory manner 
for metabolites and/or additional pharmacodynamic markers.  Details of the PK and associated 
statistical analyses will be included in the Pharmacokinetic Analysis Plan and Statistical Analysis 
Plan. 
13.6 
Pharmacodynamic Analyses 
The primary endpoint, SDLP, will be analyzed using a mixed model with fixed effects for 
sequence, period, and treatment, and a random effect for subject within sequence. 
Secondary endpoints will be evaluated similarly, however Lane Exceedance will be log 
transformed (more specifically 1n(x+1)) prior to analyses.  Pair-wise comparisons for readiness 
to drive will be analyzed using McNemar test. 
Secondary Endpoints: 
 Sleepiness Endpoint - KSS 
 Self-reported readiness to drive (“Right now do you feel safe to drive?) 
 VAS to assess subject’s motivation and self-appraisal of their driving performance 
 Performance Endpoints 
 CogScreen SDC test 
o CogScreen SDC test 
o Number of correct responses  
o Response Accuracy 
o Standard deviation of reaction time 
 Driving Performance Endpoints 
 Lane exceedance; including number, maximum, duration, and area of exceedance 
 Ratio above speed limit, excessive speed count, excessive speed ratio 
 Average speed, speed deviation, speed count, speedings ratio 
 Excessive Ay (cornering speed threshold exceeded) 
 Collision count, off-road crashes, total collisions 
 DA: Correct Responses, Omission Errors, Commission Errors, Reaction Time, Standard 
Deviation of Reaction Times 
 Single-dose plasma drug levels and driving performance 
For the primary and secondary endpoints, pair-wise comparisons (hypothesis tests) of differences 
in means, and 95 % confidence intervals on differences will be provided for: 
1. Lasmiditan 50 mg versus placebo 


Protocol:  COL MIG-106 
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6 December 2016 
Confidential 
Page 47 of 55 
2. Lasmiditan 100 mg versus placebo  
3. Lasmiditan 200 mg versus placebo  
4. Alprazolam 1.0 mg versus placebo 
5. Lasmiditan 50 mg versus alprazolam 1.0 mg  
6. Lasmiditan 100 mg versus alprazolam 1.0 mg 
7. Lasmiditan 200 mg versus alprazolam 1.0 mg 
In addition, pair-wise within-subject differences in SDLP greater than 4.4 cm in absolute value 
(equal to the previously found difference between placebo and 0.05% BAC for the CRCDS) will 
be compared using McNemar (MM) test[6].  Furthermore, these pair-wise, within subject 
differences in SDLP will be tested for symmetry about zero using the maximally selected 
McNemar test. 
14 
CLINICAL SUPPLIES 
14.1 
Product Description 
Lasmiditan 50, 100, and 200 mg tablets and alprazolam 1.0 mg tablets will be provided for the 
study by the Sponsor.  
  
14.2 
Storage Requirements 
Study drug supplies should be stored at room temperature and locked in a secure cabinet or 
room. Only the Investigator or designated third party study personnel will have access to study 
drug.  Only the unblinded third party dispenser(s) will have access to randomization codes and 
study drug assignments.  
14.3 
Accountability 
The Investigator or designated study personnel is responsible for keeping accurate records of the 
clinical supplies received from the Sponsor and the study drug administered to each subject. The 
study monitor(s) will review study drug records periodically during the conduct of the study. At 
the end of the study, all partial and empty containers must be returned to the Sponsor or they 
must be destroyed at the clinical study site according to site standard operating procedures 
(SOPs). Records of destruction of study drug at the study site must include bottle identifying 
information and number of tablets in each bottle.  
In accordance with Good Pharmacy Practices, gloves should always be worn by study personnel 
when directly handling investigational products.   


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CoLucid Pharmaceutical Inc. 
6 December 2016 
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Page 48 of 55 
15 
BIOLOGICAL SPECIMENS 
Whole blood samples and urine samples will be collected as outlined in the study flow chart for 
clinical chemistry, hematology, pharmacokinetics, and urinalysis. 
It is the responsibility of the Investigator to ensure that all personnel who will be handling, 
packaging, and/or shipping clinical specimens act in conformance with International Air 
Transport Association (IATA) regulations relating to the handling and shipping of hazardous 
goods.  
16 
CLINICAL AND LABORATORY DATA COLLECTION 
16.1 
Case Report Forms 
An eCRF will be completed for each subject. All appropriate subject data gathered during the 
study will be recorded in English on these forms. 
Whenever possible, all information requested on an eCRF should be completed. If information is 
not available, it should be documented as such. For all electronic based data fields, a tracking 
system for changes (i.e., an audit system) must be available. 
The completed eCRFs for this study are the property of CoLucid Pharmaceuticals, Inc. and 
should not be made available to third parties, except for authorized representatives of appropriate 
health/regulatory authorities, without written permission from CoLucid Pharmaceuticals, Inc. 
16.2 
Laboratory Results 
Laboratory tests (clinical chemistry, hematology and urinalysis) will be analyzed by a certified 
laboratory and reported to the clinical site as results are generated. The Investigator will review 
and comment on any laboratory value reported outside the normal range provided by the 
laboratory. The laboratory data must be signed and kept in the study subject file at the site for the 
Sponsor and will represent the source data. 


Protocol:  COL MIG-106 
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6 December 2016 
Confidential 
Page 49 of 55 
17 
STUDY DOCUMENTATION  
17.1 
Source Documents 
Source documents may include, but are not limited to, laboratory reports, ECG tracings, x-rays, 
radiologist reports, biopsy reports, ultrasound photographs, clinic notes or pharmacy records and 
any other similar reports or records of any procedure performed in accordance with the protocol. 
Source documents may also include eCRFs or electronic devices when information is recorded 
directly onto such forms or devices. 
Whenever possible, the original recording of an observation should be retained as the source 
document; however, a photocopy is acceptable provided that it is a clear, legible, and exact 
duplication of the original document. 
17.2 
Access to Records 
As required by the International Conference on Harmonization-Good Clinical Practice 
(ICH-GCP) guidelines and regulatory authorities the Investigator will allow Sponsor’s 
representative(s) direct access to all pertinent medical records in order to allow for the 
verification of data gathered in the eCRFs and for the review of the data collection process. The 
records, including source documentation, must also be available for inspection by relevant 
regulatory health authorities. 
17.3 
Retention of Records 
All essential documents and records will be maintained at Algorithme Pharma for a period of 5 
years.  These documents may be retained for a longer period if required by the applicable 
regulatory requirement(s) or if needed by the Sponsor. 
18 
INSTITUTIONAL REVIEW BOARD (IRB) 
The Investigator is responsible for obtaining an approval for conduct of the study from the IRB, 
as well as approval of all subsequent major changes to the study, in compliance with local law. 
These approvals must be forwarded to the Sponsor. The IRB will comply with all federal, state, 
and local laws. Particular attention is drawn to the Food and Drug Administration (FDA) 
Regulation for IRB (21 CFR, Part 56 and ICH GCP guidelines). 
The Investigator shall also obtain from the IRB and submit to the Sponsor, a signed statement 
indicating that it complies with Good Clinical Practices. 


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19 
ETHICAL CONDUCT OF THE STUDY 
The study will be performed according to the Declaration of Helsinki, latest edition (Edinburgh, 
Scotland, October 2000) with approval from the IRB. 
20 
INFORMED CONSENT 
It is the responsibility of the Investigator to give each potential study subject, prior to inclusion 
into the study, full and adequate verbal and written information regarding the objectives and 
procedures of the study. The study subjects must be informed about their right to withdraw from 
the study at any time. It is the responsibility of the Investigator (who may delegate this task to 
other members of the study team) to obtain signed informed consent from all study subjects 
before any study related assessments are performed. Consent must be documented by the 
subject’s dated signature on an informed consent form along with the dated signature of the 
person conducting the consent discussion. A copy of the signed and dated consent form should 
be given to the subject before participation in the trial. 
The initial informed consent form and any subsequent revised written informed consent form, 
and any written information provided to the subject must receive the IRB approval/favorable 
opinion in advance of use. 
21 
CONFIDENTIALITY 
21.1 
Confidentiality of Data 
By signing this protocol, the Investigator affirms to the Sponsor that information furnished to the 
Investigator by the Sponsor will be maintained in confidence and such information will be 
divulged to the IRB and FDA, or similar or expert committee; affiliated institution; and 
employees only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution and employees. Data generated by this study will be considered 
confidential by the Investigator, except to the extent that it is included in a publication with prior 
approval of the Sponsor.  
21.2 
Confidentiality of Subject Records 
By signing this protocol, the Investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC or regulatory agency representatives may consult and/or copy study documents in order 
to verify case report form data. By signing the consent form, the subject agrees to this process. If 
study documents will be photocopied during the process of verifying case report form 
information, the subject will be identified by subject number only, full names/initials will be 
masked prior to transmission to the Sponsor, IRB/IEC or regulatory agency. 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 51 of 55 
22 
COMPLIANCE WITH LAW, AUDIT, AND DEBARMENT 
By signing this protocol, the Investigator agrees to conduct the study in an efficient and diligent 
manner and in conformance with this protocol; generally accepted standards of GCP; and all 
applicable local laws, rules and regulations relating to the conduct of the clinical study. 
The Investigator also agrees to allow monitoring, audits, IRB review and regulatory agency 
inspection of trial-related documents and procedures and provide for direct access to all 
study-related source data and documents including access to the electronic data base for the 
study. 
The Investigator shall prepare and maintain complete and accurate study documentation in 
compliance with GCP standards and applicable local laws, rules and regulations; and, for each 
subject participating in the study, provide all data, and upon completion or termination of the 
clinical study submit any other reports to the Sponsor as required by this protocol or as otherwise 
required pursuant to any agreement with the Sponsor. 
Study documentation will be promptly and fully disclosed to the Sponsor by the Investigator 
upon request and also shall be made available at the Investigator’s site upon request for 
inspection, copying, review and audit at reasonable times by representatives of the Sponsor or 
any regulatory agencies. The Investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor as a result of an audit to cure deficiencies in the study documentation 
and eCRFs. 
ICH-GCP guidelines recommend that the Investigator inform the subject’s primary physician 
about the subject’s participation in the study if the subject has a primary physician and if the 
subject agrees to the primary physician being informed. 
The Investigator will promptly inform the Sponsor of any regulatory agency inspection 
conducted for this study and provide the final results (i.e. final observations and responses). 
Persons debarred from conducting or working on clinical studies by any court or regulatory 
agency will not be allowed to conduct or work on this study. The Investigator will immediately 
disclose in writing to the Sponsor if any person who is involved in conducting the study is 
debarred or if any proceeding for debarment is pending or, to the best of the Investigator’s 
knowledge, threatened. 
In the event the Sponsor prematurely terminates a particular study site, the Sponsor will 
promptly notify the IRB/IEC. 


Protocol:  COL MIG-106 
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6 December 2016 
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Page 52 of 55 
23 
QUALITY CONTROL AND QUALITY ASSURANCE 
Designated personnel from Algorithme Pharma will be responsible for maintaining quality 
assurance (QA) and quality control (QC) systems to ensure that the trial is conducted and data 
are generated, documented and reported in compliance with the protocol, ICH Guideline E6 for 
Good Clinical Practices. 
24 
PUBLICATIONS 
No publication or disclosure of study results will be permitted, except under the terms and 
conditions of a separate, written agreement between Sponsor and the Investigator and/or the 
Investigator’s institution. The Sponsor must have the opportunity to review and approve all 
proposed abstracts, manuscripts, or presentations regarding this study prior to submission for 
publication/presentation. Any information identified by the Sponsor as confidential must be 
deleted prior to submission. 


Protocol:  COL MIG-106 
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6 December 2016 
Confidential 
Page 53 of 55 
25 
REFERENCES 
1. Steiner, TJ, Stovner, LJ, Birbeck GL, Migraine: The seventh disabler. Cephalalgia 
2013;0:1-2. 
2. Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, et al., 
Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. 
Cephalalgia 2010;30(10):1159-1169. 
3. Shepheard S, Edvinsson L, Cumberbatch M, Williamson D, Mason G, Webb J, et al., 
Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370. 
Cephalalgia 1999;19(10):851-858. 
4. Goadsby PJ, Classey JD, Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F 
receptor inhibitory effects on trigeminal neurons with craniovascular input. Neuroscience 
2003;122(2):491-498. 
5. Cohen ML, Johnson KW, Schenck KW, Phebus LA, Migraine therapy: relationship 
between serotonergic contractile receptors in canine and rabbit saphenous veins to human 
cerebral and coronary arteries. Cephalalgia 1997;17(6):631-638. 
6. CRCDS Operations Manual.  Cognitive Research Corporation. Data on file. 
7. Siemen A, Gargano C, Cha J, Drexel M, Bautmans A, heirman I, Laethem T, Hochadel 
T, Gheyle L, Bleys K, Beals C, Stoch A, Kay G, & Struyk A. (2015). A randomized, 
crossover, placebo-controlled clinical trial to assess the sensitivity of the CRCDS Mini-
Sim to the next-day residual effects of zopiclone. Therapeutic Advances in Drug Safety, 
6 (3), 86-97. 
8. Akerstedt T, Gillberg M.  (1990).  Subjective and objective sleepiness in the active 
individual.  International Journal of Neuroscience, 52, 29–37. 
9. Kaida M, Takahashi T, Åkerstedt A, Nakata Y, Otsuka T,  Haratani K, et al. (2006).  
Validation of the Karolinska sleepiness scale against performance and EEG variables.  
Clinical Neurophysiology, 117, 1574–81. 
10. Wechsler, D. (1981). Wechsler Adult Intelligence Scale-Revised. San Antonio: 
Psychological Corporation.  
 


Protocol:  COL MIG-106 
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6 December 2016 
Confidential 
Page 54 of 55 
26 
SCHEDULE OF ACTIVITIES 
Study Procedures 
Screenin
g 
(Within 
28 Days 
Prior to 
1st 
Dose) 
(Visit 1) 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Follow
-
Up/E
OS 
Day- 
1 
(V2) 
Day 
1 
(V3) 
Day 
2 
(V4) 
Day 
6 
(V5) 
Day 
7 
(V6) 
Day 
8 
(V7) 
Day 
13 
(V8) 
Day 
14 
(V9) 
Day 
15 
(V1
0) 
Day 
20 
(V1
1) 
Day 
21 
(V1
2) 
Day 
22 
(V1
3) 
Day 
27 
(V14) 
Day 
28 
(V15) 
Day 
29 
(V16
) 
Day 35 
(Visit 
17) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Social history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Eligibility 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Weight/Height1 (BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Drug and alcohol screen  
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Serum Pregnancy Test 
X 
X9 
 
 
X9 
 
 
X9 
 
 
X9 
 
 
X9 
 
 
X 
Clinical safety labs  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X2 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Epworth Sleepiness Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Twelve-lead ECG3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs4 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
Temperature 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission to clinic5 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Discharge from clinic6 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Study Drug 
Administration 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
PK sampling7 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CogScreen SDC 
Training/Practice 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Driving Sim 
Training/Practice 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Simulator Sickness 
Questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KSS8 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Self Perceived 
Questionnaire (safe to 
drive) 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CVDA Drive 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 


Protocol:  COL MIG-106 
CoLucid Pharmaceutical Inc. 
6 December 2016 
Confidential 
Page 55 of 55 
VAS 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CogScreen SDC Test 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
C-SSRS 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Adverse event 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant meds 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1  Height and BMI will be measured at Screening only. 
2  Safety labs (hematology,  chemistry and urinalysis) at Screening and Day 35 or EOS only. 
3  Twelve-lead ECG will be obtained at Screening and Day 35 or EOS only. 
4  Vital signs will be collected at Screening, CRU check-in on Days -1, 6, 13, 20, and 27, predose and 1.17 hours post dose on Days 1, 7, 14, 21, and 28, and at 
Follow-up/Day 35 or EOS. 
5  Subjects will be inpatient on Days -1, 6, 13, 20, and 27.   
6  Subjects will be discharged approximately 24 hours post-dose. 
7  Plasma PK samples for lasmiditan levels will be collected at the following time-points: Days 1, 7, 14, 21, and 28 pre-dose (within 30 minutes before dosing) 
and 2.58 hours (155 minutes -15 to +30 minutes) post dosing. 
8  KSS is performed before each drive. 
9  A serum pregnancy test will be performed upon admission to the unit for females of child-bearing potential.  
*Days may vary depending on the exact wash-out period. 
 

SAP_000.pdf: 
Statistical Analysis Plan  H8H-CD-LAHG (COL MIG-106) 
A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, Cross-Over Study Assessing 
the Effects of Lasmiditan on Simulated Driving Performance in Normal Healthy Volunteers 
NCT03012334 
Approval Date: 23-June-2017


Lasmiditan 
Clinical Study Report - Protocol COL MIG-106 
Eli Lilly and Company 
 
 
CONFIDENTIAL 
107 
 
16.1.9 
Documentation of Statistical Methods 
 
16.1.9.1 
Statistical Analysis Plan 
16.1.9.2 
MiniSim Drive Summary Measures 
 
 


Lasmiditan 
Clinical Study Report - Protocol COL MIG-106 
Eli Lilly and Company 
 
 
CONFIDENTIAL 
108 
 
16.1.9.1 Statistical Analysis Plan 
 
The Safety Statistical Analysis Plan dated 23 June 2017 is attached. 
 


 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
For: 
CoLucid Pharmaceuticals, Inc. 
 
SPONSOR PROTOCOL No. COL MIG-106 
 
A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, 
Cross-Over Study Assessing the Effects of Lasmiditan on Simulated 
Driving Performance in Normal Healthy Volunteers 
Algorithme Project No. CUD-P8-917 
 
Prepared by:  
Algorithme Pharma 
575 Armand-Frappier 
Laval, Quebec 
Canada, H7V 4B3 
 
Cognitive Research Corporation 
200 Central Ave, Suite 1230 
Saint Petersburg, Florida 33701 
 
Version: Final 1.0 
Date: 2017/06/23  
 
 


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We have carefully read this Statistical Analysis Plan ana agree it contains the necessary infonnaiion required to handle !he 
statistical analysis of study data. 
On behalf of the Sponsor. 
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Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
4 
CONTENTS 
STATISTICAL ANALYSIS PLAN APPROVAL 
2 
VERSION CONTROL 
3 
ABBREVIATIONS 
6 
1. 
INTRODUCTION 
7 
2. 
STUDY OBJECTIVES 
8 
Primary Objectives 
8 
Secondary Objective 
8 
3. 
STUDY DESIGN 
9 
General Description 
9 
Study procedures 
10 
Randomization and Unblinding Procedure 
10 
4. 
STUDY ENDPOINTS 
11 
Primary Endpoint 
11 
Secondary Endpoints 
11 
Safety Endpoints 
11 
Pharmacokinetic Endpoints 
11 
Sample Size Determination 
11 
5. 
ANALYSIS POPULATIONS 
13 
6. 
STATISTICAL METHODOLOGY 
14 
Analysis Time Points 
14 
Methods for Handling Missing Data 
14 
7. 
STUDY SUBJECTS 
15 
Disposition 
15 
Protocol Deviations 
15 
8. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
16 
Demographic and Background Characteristics 
16 
Lifestyle 
16 
Medical/Social history 
16 
Prior Medication 
16 
9. 
PHARMACOKINETICS AND PHARMACODYNAMIC ANALYSIS 
17 
Pharmacokinetic Analysis 
17 
Pharmacodynamic Analysis 
17 
Statistical Analysis 
18 
10. 
SAFETY 
19 
Adverse Events 
19 
Concomitant Medications 
19 
Extent of Exposure 
20 
Clinical Laboratory Evaluations 
20 
Vital Signs 
20 
Electrocardiogram 
20 
Physical Examination Findings 
20 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
21 
Epworth Sleepiness Scale 
21 


 
Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
5 
Simulator Sickness Questionnaire 
21 
11. 
INTERIM ANALYSES AND DATA SAFETY MONITORING 
22 
12. 
CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
23 
13. 
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
24 
14. 
REFERENCE 
25 
PLANNED TABLES 
26 
PLANNED LISTINGS 
30 
APPENDIX A 
31 
STUDY SCHEDULES 
31 
APPENDIX B 
33 
TABLE SHELLS 
33 
APPENDIX C 
58 
PHARMACOKINETIC OUTPUTS SHELLS 
58 
APPENDIX D 
61 
LISTING SHELLS 
61 
 
 
 


 
Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
6 
ABBREVIATIONS 
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
ATC 
Anatomical/Therapeutic/Chemical 
BMI 
Body Mass Index 
CI 
Confidence Interval 
Cm 
Centimeter 
CNS 
Central Nervous System 
CRCDS-MiniSim 
Cognitive Research Corporation Driving Simulator-MiniSim 
CRF 
Case Report Form 
CS 
Clinically Significant 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CSR 
Clinical Study Report 
CVDA 
Country Vigilance-Divided Attention 
DA 
Divided Attention 
EOS 
End of Study 
ICF 
Informed Consent Form 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
kg/m2 
Kilogram per meter squared 
Km 
Kilometer 
NCS 
Not Clinically Significant 
NI 
Non-inferiority 
PK 
Pharmacokinetic(s) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDC 
Symbol Digit Coding 
SDLP 
Standard deviation of lateral position 
SE 
Standard Error 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TFLs 
Tables, Figures, and Listings 
VAS 
Visual Analog Scale 
WHO-DDE 
WHO Drug Dictionary Enhanced 
 
 
 
 
 
 
 


 
Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
7 
1. 
INTRODUCTION 
 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and procedures to be implemented for 
the analyses of data from Protocol No. COL MIG-106. The analyses described in the SAP are based upon the final protocol 
(Amendment 1) dated 2017/01/12.   
 
 


 
Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
8 
2. 
STUDY OBJECTIVES 
Primary Objectives 
The primary objective of this study is to determine the effects of acute doses of lasmiditan 50 mg, 100 mg and 200 mg compared 
to placebo and positive control (alprazolam 1.0 mg) on simulated driving performance in healthy subjects as measured by standard 
deviation of lateral position (SDLP) using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim). 
Secondary Objective 
The secondary objectives of the study are to determine the effects of lasmiditan 50 mg, 100 mg, and 200 mg compared to placebo 
and positive control (alprazolam 1.0 mg) on other measures of simulated driving performance (e.g., speed deviation, lane 
exceedance and other measures of lane position and speed control, cornering, collisions, and divided attention [DA]), CogScreen 
Symbol Digit Coding (SDC) test, and self-report measures (i.e., Karolinska Sleepiness Scale (KSS), Visual Analog Scales 
addressing motivation and performance, and if the subject feels safe to drive). 
  
 


 
Research Protocol No CUD-P8-917 | Sponsor Project No COL MIG-106| Version FINAL 1.0 | 2017/06/13 
9 
3. 
STUDY DESIGN  
General Description 
This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design with 5-period (full) crossover study 
with subjects randomized to treatment sequences. Subjects will complete all 5 Periods within the treatment sequence that they are 
randomized to. 
The treatments are: 
 
Treatment A: Lasmiditan 50 mg 
 
Treatment B: Lasmiditan 100 mg 
 
Treatment C: Lasmiditan 200 mg 
 
Treatment D: Alprazolam 1 mg 
 
Treatment E: Placebo 
Subjects will be randomized equally into one of ten treatment sequences: 
Treatment 
Sequence 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
1 
A 
B 
E 
C 
D 
2 
B  
C 
A 
D 
E 
3 
C 
D 
B 
E 
A 
4 
D 
E 
C 
A 
B 
5 
E 
A 
D 
B 
C 
6 
D 
C 
E 
B 
A 
7 
E 
D 
A 
C 
B 
8 
A 
E 
B 
D 
C 
9 
B 
A 
C 
E 
D 
10 
C 
B 
D 
A 
E 
 
Each Period including washout will be approximately 7 days in duration. 
Study drug will be administered by site staff on Day 1 of each Period. Subjects will wear a blindfold when taking each dose to 
maintain the blind. The tablet size and shape are deemed similar enough to maintain the blind with a blindfolded subject. 
CRCDS-MiniSim testing is conducted 1.5 hours post-dose (on Days 1, 7, 14, 21, and 28). 
Schematic of Design: 
Period 1  →   Washout 1  →    Period 2  →   Washout 2   →  Period 3 →   Washout 3   →  Period 4 →   Washout 4   →  Period 5   →   EOS 
Day 1 
    Days 2-6             Day 7 
 Days 8-13           Day 14         Days 15-20         Day 21          Days 22-27       Day 28           Day 35 
A sufficient number of subjects will be enrolled to complete 80 healthy volunteers in the 5-period crossover study. 
The positive control (alprazolam 1.0 mg) is included to establish the sensitivity of the study endpoints to detecting residual sedation. 
The total duration of study treatment for a participant will be approximately 5 weeks. The total duration of study participation will 
be in the range of 5-9 weeks depending on the duration of the screening period. 


 
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Study procedures 
For complete details on the study assessments to be performed for the study, refer to Appendix A.  
Randomization and Unblinding Procedure 
Prior to dosing, subjects will be randomly assigned to one of ten treatment sequences and dosed with study medication (lasmiditan, 
alprazolam or placebo) based upon a randomization scheme provided by Algorithme Pharma. Only the qualified person(nel) 
assigned to prepare and administer the study treatment will have access to the randomization schedule and dispensing records 
during the study period. 
 
Subjects will wear a blindfold when taking each dose to maintain the blind. The tablet size and shape are deemed similar enough 
to maintain the blind with a blindfolded subject. Dosing will be observed by a study staff member (qualified party dispenser); no 
other study personnel will be present at the time of dosing. 
 
  
 


 
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4. 
STUDY ENDPOINTS 
Primary Endpoint 
The primary endpoint for this study is simulated driving performance as measured by SDLP using the CRCDS-MiniSim. 
Secondary Endpoints 
The secondary endpoints for this study include other measures of simulated driving performance, KSS and CogScreen SDC test. 
 
Sleepiness Endpoint – KSS 
 
Self-reported readiness to drive (“Right now do you feel safe to drive?) 
 
Visual Analog Scales (VAS) to assess subject’s motivation and self-appraisal of their driving performance 
 
Performance Endpoints 
 
CogScreen SDC test 
o 
Number of correct responses 
o 
Response Accuracy 
o 
Standard deviation of reaction time 
 
Driving Performance Endpoints 
 
Lane exceedance; including number, maximum, duration, and area of exceedance 
 
Ratio above speed limit, excessive speed count, excessive speed ratio 
 
Average speed, speed deviation, speed count, speedings ratio 
 
Excessive Ay (cornering speed threshold exceeded) 
 
Collision count, off-road crashes, total collisions 
 
DA: Correct Responses, Omission Errors, Commission Errors, Reaction Time, Standard Deviation of Reaction 
Times 
 
Single-dose plasma drug levels and driving performance 
Safety Endpoints 
Safety endpoints include: 
 
Adverse Events  
 
Clinical Laboratory Tests (hematology, chemistry, urinalysis) 
 
Vital Signs 
 
Physical examination  
 
Concomitant medication 
 
ECGs 
 
C-SSRS 
The details of the safety endpoints’ assessment are presented in Section 10. 
Pharmacokinetic Endpoints 
The pharmacokinetic endpoint for this study is plasma lasmiditan concentration data. 
Sample Size Determination 
This study is designed to test non-inferiority of lasmiditan doses relative to placebo, with an alprazolam test versus placebo to 
confirm the sensitivity of the simulator to detect treatment effects.  
The following assumptions were made in the sample size computation:  
(a) within-subject standard deviation for SDLP is approximately 6 cm;  


 
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(b) the true difference between lasmiditan doses and placebo is 0;  
(c) the non-inferiority (NI) margin is proposed to be 4.4 cm, which is the effect seen with 0.05% of blood alcohol content 
(BAC).  
Under these assumptions, a sample of 80 subjects would provide in excess of 90% power to establish non-inferiority of any given 
dose of lasmiditan compared to placebo in terms of the primary end point, SDLP. This sample size is considered more than 
adequate to detect alprazolam differences from placebo, which are anticipated to exceed the NI margin. 
 


 
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5. 
ANALYSIS POPULATIONS 
 
Safety Population: 
All subjects who are treated with study medication will be included in the safety population. This population will be used for all 
demography, background and safety analyses.  
Intent-to-treat (ITT) Population: 
All subjects who are randomized and treated will be included in the ITT Population. This population will be used for efficacy 
analyses. Subjects will (in general) be included in all analyses for which data are non-missing. 
Pharmacokinetics (PK) Population: 
All subjects with evaluable PK data will be included in the pharmacokinetic population.  
 
 


 
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6. 
STATISTICAL METHODOLOGY 
 
All analyses will be conducted using the SAS software, version 9.4, or higher 
Adverse events and medical history will be classified using the standard MedDRA terminology version 19.1.  
Prior and concomitant medications will be coded with the WHO-DDE dictionary version March 01, 2016. 
In general, all summary tables will be presented for safety population. Summaries for adverse events will be presented by 
treatment.  
In general, the data listings will include all enrolled subjects up to the point of study completion or discontinuation; exceptions will 
be listings pertaining to a subset of subjects only (e.g., subjects with blood sampling time deviations) or a subset of records/events 
(e.g., abnormal laboratory values). 
Categorical variables will be summarized using the PROC FREQ procedure. Continuous variables will be summarized using the 
PROC UNIVARIATE, MIXED, and/or MEANS procedures. For log-transformed endpoints, geometric mean will also be presented. 
The following general comments also apply to all statistical analyses and data presentations: 
 
Duration variables in days will be calculated using the general formula: (end date - start date) +1. 
 
Individual subject listings of all data represented on the CRFs will be provided to facilitate the investigation of 
tabulated values and to allow for the clinical review of all efficacy and safety parameters. 
 
When assessments are repeated for a given timepoint, only the result which is closest to the dosing time will 
be included in the summary tables. 
The analyses described in this plan are considered a priori, that they have been defined prior to database lock.  Any analyses 
performed subsequent to database lock will be considered post hoc and exploratory.  Post hoc analyses will be labeled as such in 
the corresponding statistical output and identified in the clinical study report (CSR). 
Analysis Time Points  
Unless otherwise specified, the baseline value will be defined as the last non-missing evaluation prior to the first dose of study 
medication. 
Methods for Handling Missing Data  
No imputations of values for missing data will be performed. All data recorded on the case report form will be included in the listings 
that will accompany the CSR.   
For subjects that have incomplete data within an assessment, data will be listed but not summarized and/or analyzed for that 
assessment. 
 
 


 
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7. 
STUDY SUBJECTS 
Disposition 
The subject disposition will be summarized for all subjects enrolled in this study, including: 
 
The number of subjects screened; 
 
The number of screen failure subjects; 
 
The number of subjects randomized; 
 
The number and percentage of subjects who completed the study; 
 
The number and percentage of subjects discontinued from the study by primary reason for discontinuation and overall; 
 
The number and percentage of subjects included in each of the safety, ITT and PK populations. 
The percentages will be calculated using the number of subjects randomized as denominator. 
A listing of subject’s disposition will be provided. A listing of subjects included in each of the analysis populations will also be 
provided. 
Protocol Deviations 
Inclusion/exclusion criteria violations will be presented in a listing. 
 
 


 
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8. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and Background Characteristics 
Demographic data and baseline characteristics will be presented in a data listing and summarized in a table. Quantitative 
assessments to be summarized are age, height, body weight and body mass index (BMI) at screening. Subject demographics 
include sex, age, ethnicity, and race. Baseline characteristics include height, weight, and BMI. 
Lifestyle 
Alcohol and smoking intake history will be recorded and presented in separate listings. 
Medical/Social history  
Any medical history findings will be recorded and presented in a listing. The listing will include the coding terms (e.g., SOC and 
Preferred Term).  
Prior Medication 
Any medications taken including prescription, nonprescription, OTC (cold and antacid medications), dietary supplements, vitamins 
or herbal medications from screening to the first dose of the study drug will be recorded and presented as prior medications in a 
listing. The listing will include the coding terms (e.g., ATC and Preferred Term).   
 
 
 


 
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9. 
PHARMACOKINETICS AND PHARMACODYNAMIC ANALYSIS 
Pharmacokinetic Analysis 
Blood samples for the determination of plasma lasmiditan concentrations will be drawn at the following time points following each 
dose:  
 
Days 1, 7, 14, 21, and 28 pre-dose (within 30 minutes prior to dose) of each period  
 
Days 1, 7, 14, 21, and 28 of each period at 155 minutes (-15 to +30 minutes) after dosing 
A summary table will be provided summarizing each time point by treatment. 
Pharmacodynamic Analysis 
Primary Analysis: 
The primary endpoint, SDLP, will be analyzed using a normal theory mixed effects model with fixed effects for sequence, period, 
and treatment, and a random effect for subject within sequence.  A variance component covariance structure and Kenward-Roger 
degrees of freedom will be used.    
Pair-wise comparisons (hypothesis tests) of differences in means, and 95 % confidence intervals on differences will be provided 
for: 
1. 
Lasmiditan 50 mg versus placebo 
2. 
Lasmiditan 100 mg versus placebo  
3. 
Lasmiditan 200 mg versus placebo  
4. 
Alprazolam 1.0 mg versus placebo 
5. 
Lasmiditan 50 mg versus alprazolam 1.0 mg  
6. 
Lasmiditan 100 mg versus alprazolam 1.0 mg 
7. 
Lasmiditan 200 mg versus alprazolam 1.0 mg 
In addition, pair-wise within-subject differences in SDLP greater than 4.4 cm in absolute value (equal to the previously found 
difference between placebo and 0.05% BAC for the CRCDS) will be compared using McNemar (MM) test.  Furthermore, these 
pair-wise, within subject differences in SDLP will be tested for symmetry about zero (Laska 2012) using the maximally selected 
McNemar test. 
Summary statistics will be provided (mean, SD, median, minimum, maximum) for SDLP for each time point and treatment group.  
Figures will be provided for the within subject difference scores by treatment and day as both a histogram and scatter plot.  Data 
listings for driving simulator data will be provided. 
 
Secondary Analyses Performed as the Primary Analysis: 
Secondary endpoints of VAS, SDC, and driving performance endpoints will be evaluated and presented similarly, however Lane 
Exceedance will be log transformed (more specifically ln(x+1)) prior to analyses.   
Tables will be presented in the same format as the primary output for: 
 
Visual Analog Scales (VAS) to assess subject’s motivation and self-appraisal of their driving performance 
 
KSS 
 
Performance Endpoints 
 
CogScreen SDC test 
o 
Number of correct responses 


 
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o 
Response Accuracy 
o 
Standard deviation of reaction time 
 
Driving Performance Endpoints 
 
Lane exceedance; including number, maximum, duration, and area of exceedance 
 
Ratio above speed limit, excessive speed count, excessive speed ratio 
 
Average speed, speed deviation, speed count, speedings ratio 
 
Excessive Ay (cornering speed threshold exceeded) 
 
DA: Correct Responses, Omission Errors, Commission Errors, Reaction Time, Standard Deviation of Reaction 
Times 
A data listing for the two VASs and SDC results will be provided 
 
Additional Secondary Analyses: 
Driving Performance Collision count, off-road crashes, Total Collisions: 
Summary statistics will be provided (mean, SD, median, minimum, maximum) for collision count, off-road crashes, and total number 
of collisions for each time point and treatment group.  Additionally, differences in number of collisions/crashes for each pair-wise 
comparison will be provided with their corresponding Wilcoxon Signed Rank p-value.  A bar chart will be provided pooling total 
number of collisions by 0, 1, 2, or >=3 for all 3 treatment groups. 
Self-reported readiness: 
Pair-wise comparisons for readiness to drive will be analyzed using McNemar’s test.  A bar graph for percentage of subjects 
reporting not safe to drive will be reported by treatment and day.   
Plasma drug levels: 
The decision as to which plasma samples collected will be assayed for evaluation of pharmacokinetics will be determined by 
CoLucid Pharmaceuticals, Inc. The correlations between single-dose plasma drug concentrations the morning of the driving 
simulation and the primary and key secondary end points will be evaluated, data permitting. If indicated, these samples may also 
be assayed and/or pooled for assay in an exploratory manner for metabolites and/or additional pharmacodynamic markers.   
The relationship between single-dose drug levels and all secondary endpoints (excluding self-reported readiness) will be assessed 
by correlation.  Both the Spearman and Pearson correlations will be reported.  Figures will be provided for the within subject 
difference from placebo scores by treatment and day as a scatter plot.   
Statistical Analysis  
Initially, the statistical significance of alprazolam vs. placebo (p<0.05) comparison for SDLP is necessary to validate the 
experiment as having the ability to detect effects (i.e., assay sensitivity). 
 
To address multiplicity of testing, for the primary endpoint of SDLP, ascending doses of lasmiditan will be interpreted in a 
sequential manner, starting with the 50 mg dose and proceeding to 100 mg and then 200 mg.  Doses of lasmiditan will be 
considered non-inferior to placebo if the upper 95% confidence limit on the difference in SDLP between that dose and placebo is 
less than 4.4 cm and lower doses also do not exceed the NI margin.  No adjustment to alpha levels will be made for either the 
comparison of alprazolam to placebo or to lasmiditan, or for secondary endpoints or analyses.  Formal statistical tests (where 
performed) will be two-sided and testing at the alpha=0.05 level of significance. 
 
 


 
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10. 
SAFETY 
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily 
have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (for example, 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not 
considered related to this medicinal product. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug caused the AE. ‘Reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the AE. A suspected adverse reaction 
implies a lesser degree of certainty about causality than adverse reaction, which means any AE caused by a drug.  
AEs occurring after the initiation of the treatment are referred to as treatment emergent adverse events (TEAEs). 
 
TEAEs will be assigned to a treatment based on the time of occurrence in relation to the last treatment administered prior to the 
onset of the TEAE. TEAEs will be assigned using the following rules:  
 
TEAE will be assigned to the last treatment taken by the subject where the date and time of the last treatment dosing is 
on or before of the start date and time of the event. Such assignment will be performed irrespective of any washout 
period between the start and stop dates of the TEAE.  
 
Any TEAE started after the discharge and during the follow-up period will be assigned to the last treatment that the 
subject has taken during last period. 
As an overall summary of AEs, the following will be presented by treatment and overall: 
 
Number of reported AEs;  
 
Number of reported TEAEs;  
 
Number and percentage of subjects experiencing TEAEs;  
 
Number and percentage of subjects experiencing a drug-related TEAE (i.e. those with a relationship classified as 
reasonable possibility) 
 
Number and percentage of TEAEs by relationship to study treatment (i.e. reasonable possibility, no reasonable 
possibility);  
 
Number and percentage of TEAEs by severity;  
 
Number of reported SAEs (serious adverse events);  
 
Number and percentage of subjects experiencing SAEs;  
 
Number and percentage of subjects experiencing drug-related SAEs; 
 
Number and percentage of TEAEs leading to withdrawal; and 
 
SAEs with an outcome of death.  
Frequency tables will be presented by treatment, system organ class and preferred term that summarize all Treatment Emergent 
Adverse Events (TEAEs), and SAEs. Frequency tables will also be presented by treatment, system organ class, preferred term 
and maximum severity and by treatment, system organ class, preferred term and relationship to study drug.  
Subject listings of all Adverse Events (AEs) including severity and relationship to study drug will be provided. AEs leading to 
withdrawal and SAEs will also be presented in separate listings. 
Concomitant Medications 
Medications taken after the first dose of study drug until after discharge from the study will be recorded. Concomitant medications 
will be presented in a listing. The medication name, active ingredient, dose, units, formulation, route, indication or reason taken, 
code, date and time taken will be presented. The listing will also include the coding terms (e.g., ATC and Preferred Term). 


 
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Extent of Exposure 
Details of drug dosing (actual treatment received, actual date and time of administration, dose administered, and route of 
administration) will be listed by subject. 
Clinical Laboratory Evaluations 
Planned laboratory analyses include: 
 
Blood Chemistry: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total 
and direct bilirubin, blood urea nitrogen (BUN), creatinine, gamma glutamyltransferase (GGT), glucose, potassium, 
sodium; 
 
Hematology: hemoglobin, hematocrit; platelets, prothrombin time (PT), red blood cells (RBC), white blood cells (WBC) 
with differential (absolute), 
 
Urinalysis: bilirubin, erythrocytes, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, urobilinogen 
 
Other: urine drug screen and serum pregnancy. 
Hematology, chemistry and quantitative urinalysis laboratory test results, as well as the change from baseline, will be summarized 
by sequence, parameter and visit. 
Separate listings of all individual data for urinalysis, hematology, chemistry and other laboratory tests will be presented by subject, 
laboratory test and visit. 
Subject listings of abnormal on-study laboratory values will be provided, including demographic information. Similarly, clinically 
significant on-study laboratory data will be presented in a second listing.   
Vital Signs 
Vital signs will include the measurement of blood pressure, heart rate, oral temperature, and body weight.  
For all vital signs, raw values, as well as the change from baseline, at each time point will be summarized by treatment, parameter 
and visit. Vital signs data will also be presented in a listing. 
Subject listing of abnormal on-study vital signs values (Out-of-Range – Not Clinically Significant (NCS) or Clinically Significant 
(CS)) will be provided. Similarly, CS on-study vital signs values (Out-of-Range – CS) will be presented in a second listing. 
Electrocardiogram 
A triplicate 12-lead ECG will be obtained at time points throughout the study. In some cases, repeat abnormal ECGs may be 
obtained. 
Raw values at each time point, as well as the change from baseline, will be summarized by sequence, parameter and visit and will 
also be presented in a listing. 
A subject listing of abnormal on-study ECG assessments (Abnormal – NCS or Abnormal – CS) will be provided. Similarly, CS on-
study ECG assessments (Abnormal – CS) will be presented in a second listing. 
Physical Examination Findings 
A physical examination will be conducted and results will be presented in a listing. 
A subject listing of abnormal on-study physical examination results (Abnormal – NCS or Abnormal – CS) will be provided, including 
demographic information. Similarly, CS on-study physical examination results (Abnormal – CS) will be presented in a second 
listing.  


 
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Columbia-Suicide Severity Rating Scale (C-SSRS) 
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a suicidal ideation rating scale. The scale identifies behaviors and 
thoughts that are associated with an increased risk of suicidal actions in the future. The C-SSRS will be performed at Screening, 
on Days -1, 6, 13, 20, and 27, and Day 35 or EOS. 
Subjects who answer ‘Yes’ to any of the questions on the C-SSRS questionnaire will be presented in a listing 
Epworth Sleepiness Scale 
The Epworth Sleepiness Scale assessment will be performed at Screening and results will be presented in a listing. 
Simulator Sickness Questionnaire 
A simulator sickness questionnaire will be performed at Screening and results will be presented in a listing. 
 
 


 
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11. 
INTERIM ANALYSES AND DATA SAFETY MONITORING 
 
There is no interim analysis or safety data monitoring planned for this study. 
 
 


 
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12. 
CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
 
There is no change from the planned analysis described in the protocol. 
 
 


 
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13. 
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
 
All programs used to generate statistical analyses will be validated according to Algorithme Pharma’s standard operating 
procedures. 
TFLs will be displayed on letter size paper, 8 ½ inches by 11 inches, using the Courier New font.     
In general, summary statistics for raw variables (i.e., variables measured at the study site or central laboratory) will be displayed 
as follows: if required minima, maxima, means, quartiles, standard deviations and confidence limits will be displayed to the same 
number of decimal places as the raw data; if required medians will be displayed to one additional decimal place.   
Percentages will be displayed to one decimal place. Percentages between 0 and 0.1 (exclusive) will be displayed as ‘<0.1’.  P-
values will be displayed to 3 decimal places. P-values that are less than 0.001 will be displayed as ‘<0.001’.   
The numbers of decimal places for summary statistics of derived variables (i.e., variables that are not measured by the study site 
but are calculated for analysis based on other measured variables) will be determined on a case by case basis.  In general, minima 
and maxima will be displayed to the commonly used unit of precision for the parameter. Means, medians, quartiles, and confidence 
limits will be displayed to one additional decimal place and standard deviations will be displayed to two additional decimal places. 
The formats and layouts of TFLs are provided in subsequent sections.  Actual formats and layouts may be altered slightly from 
those presented in the templates as necessary to accommodate actual data or statistics.  Minor format changes will not require 
updates to the SAP. 
The tables and listings listed below are common data displays. Their numbering and general content follow the ICH E3 guidelines.  
Some of the tables and listings may not be applicable/appropriate/necessary for a particular study.  Additional tables and listings 
may be included, provided the numbering scheme remains consistent with ICH E3. 


 
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14. 
REFERENCE 
Laska E, Meisner M, Wanderling J. A maximally selected test of symmetry about zero.  Stat Med 2012;31:3178-91. 
 
 


 
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PLANNED TABLES 
 
Demographic Data 
Table 14.1.1 
Subject Disposition – All Subjects 
Table 14.1.2.1 
Summary of Demographic Characteristics (Safety Population) 
Table 14.1.2.2 
Summary of Demographic Characteristics (Intent-to-treat Population) 
Table 14.1.2.3 
Summary of Demographic Characteristics (Pharmacokinetic Population) 
 
Efficacy Data  
Tables in this section are based on the primary efficacy population unless otherwise stated. 
Table 14.2.1.1 
Standard Deviation of Lateral Position (SDLP) 
Table 14.2.1.2.1 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Alprazolam versus Placebo) 
Table 14.2.1.2.2 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 50 mg versus Placebo)  
Table 14.2.1.2.3 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 50 mg versus Alprazolam) 
Table 14.2.1.2.4 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 100 mg versus Placebo)  
Table 14.2.1.2.5 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 100 mg versus Alprazolam) 
Table 14.2.1.2.6 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 200 mg versus Placebo)  
Table 14.2.1.2.7 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about 
Zero (ITT Population – Lasmiditan 200 mg versus Alprazolam) 
Table 14.2.2.1 
Visual Analog Scale (VAS) Motivation 
Table 14.2.2.2 
Visual Analog Scale (VAS) Self-appraisal 
Table 14.2.3.1 
Symbol Digit Coding (SDC) Number of Correct Responses 
Table 14.2.3.2 
Symbol Digit Coding (SDC) Accuracy 
Table 14.2.3.3 
Symbol Digit Coding (SDC) Standard Deviation of Reaction Time 
Table 14.2.4.1 
Driving Performance Lane Exceedance Number 
Table 14.2.4.2 
Driving Performance Lane Exceedance Maximum 
Table 14.2.4.3 
Driving Performance Lane Exceedance Duration 
Table 14.2.4.4 
Driving Performance Lane Exceedance Area of Exceedance 
Table 14.2.4.5 
Driving Performance Ratio Above Speed Limit 
Table 14.2.4.6 
Driving Performance Excessive Speed Count 
Table 14.2.4.7 
Driving Performance Excessive Speed Ratio 
Table 14.2.4.8 
Driving Performance Average Speed 
Table 14.2.4.9 
Driving Performance Speed Deviation 
Table 14.2.4.10 
Driving Performance Speed Count 
Table 14.2.4.11 
Driving Performance Speedings Ratio 
Table 14.2.4.12 
Driving Performance Excessive Ay (Cornering Speed Threshold Exceeded) 
Table 14.2.4.13 
Driving Performance Collision Count 
Table 14.2.4.14 
Driving Performance Off-road Crashes 
Table 14.2.4.15 
Driving Performance Total Collisions 
Table 14.2.4.16 
Driving Performance Divided Attention – Correct Responses 
Table 14.2.4.17 
Driving Performance Divided Attention – Omission Errors 
Table 14.2.4.18 
Driving Performance Divided Attention – Commission Errors 


 
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Table 14.2.4.19 
Driving Performance Divided Attention – Reaction Time 
Table 14.2.4.20 
Driving Performance Divided Attention – Standard Deviation of Reaction 
Time 
Table 14.2.5 
Karolinska Sleepiness Scale (KSS) 
Table 14.2.6 
Self-Reported Readiness 
Table 14.2.7.1 
Plasma Concentration by Time Point (Safety Population) 
Table 14.2.7.2 
Correlation of ln(Plasma Drug Levels) to SDLP 
Table 14.2.7.3 
Correlation of ln(Plasma Drug Levels) to Visual Analog Scale (VAS) 
Motivation 
Table 14.2.7.4 
Correlation of ln(Plasma Drug Levels) to Visual Analog Scale (VAS) Self-
appraisal 
Table 14.2.7.5 
Correlation of ln(Plasma Drug Levels) to Symbol Digit Coding (SDC) 
Number of Correct Responses 
Table 14.2.7.6 
Correlation of ln(Plasma Drug Levels) to Symbol Digit Coding (SDC) 
Accuracy 
Table 14.2.7.7 
Correlation of ln(Plasma Drug Levels) to Symbol Digit Coding (SDC) 
Standard Deviation of Reaction Time 
Table 14.2.7.8 
Correlation of ln(Plasma Drug Levels) to Driving Performance Lane 
Exceedance Number 
Table 14.2.7.9 
Correlation of ln(Plasma Drug Levels) to Driving Performance Lane 
Exceedance Maximum 
Table 14.2.7.10 
Correlation of ln(Plasma Drug Levels) to Driving Performance Lane 
Exceedance Duration 
Table 14.2.7.11 
Correlation of ln(Plasma Drug Levels) to Driving Performance Lane 
Exceedance Area of Exceedance 
Table 14.2.7.12 
Correlation of ln(Plasma Drug Levels) to Driving Performance Ratio Above 
Speend Limit 
Table 14.2.7.13 
Correlation of ln(Plasma Drug Levels) to Driving Performance Excessive 
Speed Count 
Table 14.2.7.14 
Correlation of ln(Plasma Drug Levels) to Driving Performance Excessive 
Speed Ratio 
Table 14.2.7.15 
Correlation of ln(Plasma Drug Levels) to Driving Performance Average 
Speed 
Table 14.2.7.16 
Correlation of ln(Plasma Drug Levels) to Driving Performance Speed 
Deviation 
Table 14.2.7.17 
Correlation of ln(Plasma Drug Levels) to Driving Performance Speed Count 
Table 14.2.7.18 
Correlation of ln(Plasma Drug Levels) to Driving Performance Speeding 
Ratio 
Table 14.2.7.19 
Correlation of ln(Plasma Drug Levels) to Driving Performance Excessive Ay 
(Cornering Speed Threshold Exceeded) 
Table 14.2.7.20 
Correlation of ln(Plasma Drug Levels) to Driving Performance Collision 
Count  
Table 14.2.7.21 
Correlation of ln(Plasma Drug Levels) to Driving Performance Off-road 
Crashes 
Table 14.2.7.22 
Correlation of ln(Plasma Drug Levels) to Driving Performance Total 
Collisions 
Table 14.2.7.23 
Correlation of ln(Plasma Drug Levels) to Driving Performance Divided 
Attention – Correct Responses 
Table 14.2.7.24 
Correlation of ln(Plasma Drug Levels) to Driving Performance Divided 
Attention – Omission Errors 
Table 14.2.7.25 
Correlation of ln(Plasma Drug Levels) to Driving Performance Divided 
Attention – Commission Errors 


 
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Table 14.2.7.26 
Correlation of ln(Plasma Drug Levels) to Driving Performance Divided 
Attention – Reaction Time 
Table 14.2.7.27 
Correlation of ln(Plasma Drug Levels) to Driving Performance Divided 
Attention – Standard Deviation of Reaction Time 
Table 14.2.7.28 
Correlation of ln(Plasma Drug Levels) to Karolinska Sleepiness Scale (KSS) 
Pre-Drive 
 
 
 
 
 


 
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Safety Data 
Tables in this section are based on the safety population unless otherwise stated. 
Table 14.3.1.1 
Summary of Adverse Events  
Table 14.3.1.2 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA 
Preferred Term 
Table 14.3.1.3 
Summary of Serious Adverse Events by System Organ Class and MedDRA Preferred Term 
Table 14.3.1.4 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA 
Preferred Term and Maximum Severity 
Table 14.3.1.5 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA 
Preferred Term and Relationship To Study Drug 
Table 14.3.2.1 
Listing of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.2.2 
Listing of Treatment Emergent Adverse Events Leading to Withdrawal 
Table 14.3.4.1 
Listing of Abnormal On-Study Laboratory Values 
Table 14.3.4.2 
Listing of Clinically Significant On-Study Laboratory Values 
Table 14.3.4.3 
Summary of Blood Chemistry 
Table 14.3.4.4 
Summary of Hematology 
Table 14.3.4.5 
Summary of Quantitative Urinalysis 
Table 14.3.5.1 
Listing of Abnormal On-Study Vital Signs Values 
Table 14.3.5.2 
Listing of Clinically Significant On-Study Vital Signs Values 
Table 14.3.5.3 
Summary of Vital Signs 
Table 14.3.6.1 
Listing of Abnormal On-Study ECG Assessments 
Table 14.3.6.2 
Listing of Clinically Significant On-Study ECG Assessments 
Table 14.3.6.3 
Summary of ECG Assessments 
Table 14.3.7.1 
Listing of Abnormal On-Study Physical Examination Findings 
Table 14.3.7.2 
Listing of Clinically Significant On-Study Physical Examination Findings 
 
Planned Figures 
Figure 14.2.1.1.1 
Within Subject Difference Scores in SDLP by Treatment  
Figure 14.2.1.2.1 
Within Subject Difference Scores (Alprazolam - Placebo) (ITT Population - 
Alprazolam versus Placebo) 
Figure 14.2.1.2.2 
Within Subject Difference Scores (Lasmiditan 50 mg - Placebo) (ITT 
Population – Lasmiditan 50 mg versus Placebo) 
Figure 14.2.1.2.3 
Within Subject Difference Scores (Lasmiditan 100 mg - Placebo) (ITT 
Population – Lasmiditan 100 mg versus Placebo) 
Figure 14.2.1.2.4 
Within Subject Difference Scores (Lasmiditan 200 mg - Placebo) (ITT 
Population - Lasmiditan 200 mg versus Placebo) 
Figure 14.2.7.2.1 
Within Subject Difference Scores in SDLP by Plasma Concentration for 
Lasmiditan 50 mg 
Figure 14.2.7.2.2 
Within Subject Difference Scores in SDLP by Plasma Concentration for 
Lasmiditan 100 mg 
Figure 14.2.7.2.3 
Within Subject Difference Scores in SDLP by Plasma Concentration for 
Lasmiditan 200 mg 
Figure 14.2.4.13 
Collision Count 
Figure 14.2.4.14 
Off-road Crashes 
Figure 14.2.4.15 
Total Collisions 
 
 
 


 
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PLANNED LISTINGS 
 
Listing 16.2.1 
Listing of Study Disposition 
Listing 16.2.3 
Listing of Analysis Populations 
Listing 16.2.4.1 
Listing of Demographic Characteristics 
Listing 16.2.4.2 
Listing of Screen Failure Subjects 
Listing 16.2.5.1 
Listing of Investigational Product Administration 
Listing 16.2.5.2 
Listing of Lasmiditan Plasma Concentrations 
Listing 16.2.6.1.1 
Listing of Driving Simulator Part 1 of 5  
Listing 16.2.6.1.2 
Listing of Driving Simulator Part 2 of 5  
Listing 16.2.6.1.3 
Listing of Driving Simulator Part 3 of 5  
Listing 16.2.6.1.4 
Listing of Driving Simulator Part 4 of 5  
Listing 16.2.6.1.5 
Listing of Driving Simulator Part 5 of 5  
Listing 16.2.6.2 
Listing of Karolinska Sleepiness Scale (KSS)   
Listing 16.2.6.3 
Listing of CogScreen Symbol Digit Coding (SDC)  
Listing 16.2.6.4 
Listing of Visual Analog Scale (VAS)  
Listing 16.2.7 
Listing of Adverse Events  
Listing 16.2.8.1 
Listing of Blood Chemistry 
Listing 16.2.8.2 
Listing of Hematology 
Listing 16.2.8.3 
Listing of Urinalysis 
Listing 16.2.8.4 
Listing of Urine Drug Screen 
Listing 16.2.8.5 
Listing of Pregnancy Test 
Listing 16.2.9.1 
Listing of Alcohol Habits 
Listing 16.2.9.2 
Listing of Smoking Habits 
Listing 16.2.9.3 
Listing of Prior Medication 
Listing 16.2.9.4 
Listing of Concomitant Medication 
Listing 16.2.9.5 
Listing of Physical Examination 
Listing 16.2.9.6 
Listing of Vital Signs 
Listing 16.2.9.7 
Listing of ECG Assessments 
Listing 16.2.9.8 
Listing of Screening Summary  
Listing 16.2.9.9 
Listing of Medical History 
Listing 16.2.9.10 
Listing of Columbia-Suicide Severity Rating Scale (C-SSRS) 
Listing 16.2.9.11 
Listing of Epworth Sleepiness Scale 
Listing 16.2.9.12 
Listing of Simulator Sickness Questionnaire 
 
 


 
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APPENDIX A 
STUDY SCHEDULES 
 
Study Procedures 
Screening 
(Within 28 
Days Prior 
to 1st 
Dose) 
(Visit 1) 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Follow-
Up/EOS 
Day- 
1 
(V2) 
Day 
1 
(V3) 
Day 
2 
(V4) 
Day 
6 
(V5) 
Day 
7 
(V6) 
Day 
8 
(V7) 
Day 
13 
(V8) 
Day 
14 
(V9) 
Day 
15 
(V10) 
Day 
20 
(V11) 
Day 
21 
(V12) 
Day 
22 
(V13) 
Day 
27 
(V14) 
Day 
28 
(V15) 
Day 
29 
(V16) 
Day 35 
(Visit 17) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Social history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Eligibility 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Weight/Height1 (BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Drug and alcohol 
screen  
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Serum Pregnancy Test 
X 
X9 
 
 
X9 
 
 
X9 
 
 
X9 
 
 
X9 
 
 
X 
Clinical safety labs  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X2 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Epworth Sleepiness 
Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Twelve-lead ECG3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs4 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
Temperature 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission to clinic5 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Discharge from clinic6 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Study Drug 
Administration 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
PK sampling7 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CogScreen SDC 
Training/Practice 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Driving Sim 
Training/Practice 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Simulator Sickness 
Questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KSS8 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 


 
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Self-Perceived 
Questionnaire (safe to 
drive) 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CVDA Drive 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
VAS 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CogScreen SDC Test 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
C-SSRS 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Adverse event 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant meds 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1  Height and BMI will be measured at Screening only. 
2  Safety labs (hematology, chemistry and urinalysis) at Screening and Day 35 or EOS only. 
3  Twelve-lead ECG will be obtained at Screening and Day 35 or EOS only. 
4  Vital signs will be collected at Screening, CRU check-in on Days -1, 6, 13, 20, and 27, pre-dose and 1.17 hours post dose on Days 1, 7, 14, 21, and 28, and at 
Follow-up/Day 35 or EOS. 
5  Subjects will be inpatient on Days -1, 6, 13, 20, and 27.   
6  Subjects will be discharged approximately 24 hours post-dose. 
7  Plasma PK samples for lasmiditan levels will be collected at the following time-points: Days 1, 7, 14, 21, and 28 pre-dose (within 30 minutes before dosing) and 
2.58 hours (155 minutes -15 to +30 minutes) post dosing. 
8  KSS is performed before each drive. 
9  A serum pregnancy test will be performed upon admission to the unit for females of child-bearing potential.  
*Days may vary depending on the exact wash-out period. 
 
 


 
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APPENDIX B 
TABLE SHELLS 
 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
 
Algorithme Pharma 
Project # COL MIG-106/CUD-P8-917 
 
     Page 1 of x 
 
 
 
Table 14.1.1 
 
Subject Disposition 
 
(All Subjects) 
 
 
   
   
Placebo 
Lasmiditan 
50 mg 
Lasmidit
an 100 
mg 
Lasmidit
an 200 
mg 
Alprazolam 
1 mg 
Overall 
  
  
 
 
 
 
 
 
Subjects Screened 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
 
Screen Fail 
Subjects 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
 
Subjects 
Randomized [N] 
 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
Subjects Completed 
the Study [n(%)] 
YES 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
NO 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
If No, Reason of 
Study 
Discontinuation 
[n(%)] 
Reason 1 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Reason 2 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Reason 3 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Etc. 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Number of Subjects 
Included in Each 
Analysis 
Population [n(%)] 
Safety 
Population 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Intent-to-
treat 
Population 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Pharmacokineti
c Population 
xx (xx.x) 
xx (xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx (xx.x) 
xx (xx.x) 
  
  
 
 
 
 
 
 
 
 
Note: The percentages are based on the number of subjects randomized. 


 
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Date: VERSION – YYYY-MM-
DD 
Data 
Source: 
XXXX 
 
Program Source:  XXXXX.sas 
 
CoLucid Pharmaceuticals, Inc. 
 
 
Algorithme Pharma 
Project # COL MIG-106/CUD-P8-917 
 
 
     Page 1 of x 
 
 
 
 
 


 
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Table 14.1.2.1 
 
 
Summary of Demographic Characteristics 
 
 
(Safety Population) 
 
 
   
 
 
 
 
 
 
   
Placebo 
 (N=XX) 
Lasmiditan 
50 mg 
 (N=XX) 
Lasmiditan 
100 mg 
(N=XX) 
Lasmiditan 
200 mg 
(N=XX) 
Alprazolam 
1 mg 
(N=XX) 
Overall 
(N=XX) 
   
 
 
 
 
 
 
Age (years) N 
xx 
xx 
xx 
xx 
xx 
xx 
 Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 
Gender [n(%)] MALE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 FEMALE 
 
 
 
 
 
 
  
 
 
 
 
 
 
Ethnicity [n(%)] HISPANIC/LATINO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 NOT HISPANIC/NOT LATINO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
Race [n(%)] RACE1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 RACE2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
Weight at Screening (kg) N 
xx 
xx 
xx 
xx 
xx 
xx 
 Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 
Height (cm) N 
xx 
xx 
xx 
xx 
xx 
xx 
 Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 
Body Mass Index as Screening (kg/m2) N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
  
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
 
 
Program Source:  XXXXX.sas 
 
 
 


 
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Similar Table: 
 
Table 14.1.2.2 Summary of Demographic Characteristics (Intent-to-treat Population) 
Table 14.1.2.3 Summary of Demographic Characteristics (Pharmacokinetic Population) 
 
 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
Project # COL MIG-106  
 
 
 
 
 
 
 
 
 
 
(Page x of y) 
Table 14.2.1.1 
Standard Deviation of Lateral Position (SDLP) 
(ITT Population) 
 
 
 
Placebo  
Lasmiditan 50 mg 
Lasmiditan 100 mg 
Lasmiditan 200 mg 
Alprazolam 1 mg 
Statistic 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 N 
xx 
xx 
xx 
xx 
xx 
 Mean (SD) 
xx.xxxx (xx.xx) 
xx.xxxx (xx.xx) 
xx.xxxx (xx.xx) 
xx.xxxx (xx.xx) 
xx.xxxx (xx.xx) 
 LSMeans* 
xx.xxxx 
xx.xxxx 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 Median 
xx.x  
xx.x  
xx.x  
xx.x  
xx.x  
 Min, Max 
xx.xxxx , xx.xxxx 
xx.xxxx , xx.xxxx 
xx.xxxx , xx.xxxx 
xx.xxxx , xx.xxxx 
xx.xxxx , xx.xxxx 
 
 
 
 
 
 
 
Lasmiditan 50 mg 
vs PBO  
Lasmiditan 100 mg 
vs PBO  
Lasmiditan 200 mg 
vs PBO  
Alprazolam 1 mg 
vs PBO 
Diff in LSMean 
xx.xxxx 
xx.xxxx 
xx.xxxx 
xx.xxxx 
95%CI* 
(xx.xx , xx.xx) 
(xx.xx , xx.xx) 
(xx.xx , xx.xx) 
(xx.xx , xx.xx) 
p-value* 
0.xxxx 
0.xxxx 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
 
Lasmiditan 50 mg 
vs Alprazolam 1 
mg 
Lasmiditan 100 mg 
vs Alprazolam 1 
mg 
Lasmiditan 200 mg 
vs Alprazolam 1 
mg 
 
Diff in LSMean 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 
95%CI* 
(xx.xx , xx.xx) 
(xx.xx , xx.xx) 
(xx.xx , xx.xx) 
 
p-value* 
0.xxxx 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
{Repeat table for VAS Motivation (Table 14.2.2.1), VAS self-appraisal (Table 14.2.2.2), SDC number of correct responses (Table 
14.2.3.1), SDC Accuracy (Table 14.2.3.2), SDC Standard deviation of reaction time (Table 14.2.3.3), Driving Performance Lane 
Exceedance number Table 14.2.4.1), maximum (Table 14.2.4.2), duration (Table 14.2.4.3) area of exceedance (Table 14.2.4.4), 
ratio above speed limit (Table 14.2.4.5), excessive speed count (Table 14.2.4.6), excessive speed ratio (Table 14.2.4.7), 
average speed (Table 14.2.4.8), speed deviation (Table 14.2.4.9), speed count (Table 14.2.4.10), speedings ratio (Table 
14.2.4.11), excessive ay (cornering speed threshold exceeded)(Table 14.2.4.12), Driving Performance Divided Attention – 
Correct Responses (Table 14.2.4.16), omission errors (Table 14.2.4.17), commission errors (Table 14.2.4.18) reaction time 
(Table 14.2.4.19), standard deviation of reaction time (Table 14.2.4.20)} 
 
 


 
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*Mixed effects model with fixed effects for sequence, period, and treatment, and a random effect for subject within sequence, 
variance component covariance structure, and Kenward-Roger degrees of freedom.  Estimated differences are first treatment 
label listed minus second treatment label. 
 
SAS Program Name:    
 
Date: 
 
 
 
Source Data:  Listing 16.2.6.X 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
Project # COL MIG-106  
 
 
 
 
 
 
 
 
 
 
(Page x of y) 
Table 14.2.1.2.1 
Standard Deviation of Lateral Position (SDLP) Analysis of Symmetry about Zero (ITT Population – Alprazolam versus Placebo) 
(ITT Population) 
 
Threshold 
Sign 
Low 
Neutral 
High 
McNemar 
Nominal 
P-value 
 
 
 
 
 
 
 
x.xxx 
-/+ 
xx 
xx 
xx 
x.xxxx 0.xxxxxx 
x.xxx 
-/+ 
xx 
xx 
xx 
x.xxxx 0.xxxxxx 
 
 
Repeat table for other comparisons. 
 
 
Maximally selected McNemar's test statistic (MM) Critical value for n=XX paired differences, at alpha=0.05 (two-tailed) is 
X.XXX. 
Symmetry about zero is rejected if the maximum of the McNemar's test statistics is greater than X.XXX. 
If the sum of the high and low values is less than 25, an exact two-sided p-value is computed using the binomial distribution 
(p=1/2), conditional on the sum of the high and low values (as 2 X the one-sided p-value). 
SAS Program Name:    
 
Date: 
 
 
 
Source Data:  Listing 16.2.6.1.X 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
Project # COL MIG-106  
 
 
 
 
 
 
 
 
 
 
(Page x of y) 
 
 
Table 14.2.4.13 
Driving Performance Collision Count  
(ITT Population) 
 
Placebo  
Lasmiditan 50 mg 
Lasmiditan 100 mg 
Lasmiditan 200 mg 
Alprazolam 1 mg 
Statistic 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 N 
xx 
xx 
xx 
xx 
xx 
 Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
 SD 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
 Median 
x.x 
x.x 
x.x 
x.x 
x.x 
 Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Diff in # of Collisions 
Lasmiditan 50 mg 
vs PBO  
Lasmiditan 100 mg 
vs PBO  
Lasmiditan 200 mg 
vs PBO  
Alprazolam 1 mg 
vs PBO 
 N 
xx 
xx 
xx 
xx 
 Mean 
x.x 
x.x 
x.x 
x.x 
 SD 
x.xx 
x.xx 
x.xx 
x.xx 
 Median 
 
x.x 
x.x 
x.x 
x.x 
 Min, Max 
 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
p-value* 
 
0.xxxx 
0.xxxx 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
Diff in # of Collisions 
Lasmiditan 50 mg 
vs Alprazolam 1 
mg 
Lasmiditan 100 mg 
vs Alprazolam 1 
mg 
Lasmiditan 200 mg 
vs Alprazolam 1 
mg 
 
 N 
xx 
xx 
xx 
 
 Mean 
x.x 
x.x 
x.x 
 
 SD 
x.xx 
x.xx 
x.xx 
 
 Median 
 
x.x 
x.x 
x.x 
 
 Min, Max 
 
xx, xx 
xx, xx 
xx, xx 
 
p-value* 
 
0.xxxx 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Wilcoxon Signed Ranks test. 
 
{Repeat table for off-road crashes (Table 14.2.4.14), and total collisions (Table 14.2.4.15)} 
 
SAS Program Name:    
 
Date: 
 
 
 
Source Data:  Listing 16.2.6.X 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
Algorithme Pharma 
Project # COL MIG-106/CUD-P8-917 
     Page 1 of x 
 
Table 14.3.1.1 
Summary of Adverse Events  
(Safety Population) 
 
   
   
 
 
 
 
   
Placebo 
(N=XX) 
Lasmiditan 50 mg 
(N=XX) 
Etc. 
Overall 
(N=XX) 
 
 
  
  
 
 
 
 
 Adverse Events (AEs) Reported [n] 
 
 
 
xx 
 
 
 
 
 
 
 
 
 Treatment Emergent Adverse Events (TEAEs) Reported [n] 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 Subjects With At Least One TEAE [n(%)]  [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 Subjects With At Least One Drug-Related TEAE [n(%)] [1] 
[3] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 TEAEs Relationship [2] 
 
 
 
 
 
 
Reasonable Possibility [n (%)]  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
No Reasonable Possibility 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 TEAEs Severity/Intensity [2] 
 
 
 
 
 
 
Mild [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Moderate [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Severe [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 Life-Threatening [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 Serious Adverse Events (SAEs) Reported [n] [2] 
xx 
xx 
xx 
xx 
 
  
 
 
 
 
 
 Subjects With At Least One SAE [n(%)][1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 Subjects With At Least Drug-Related SAE [n(%)][1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 Subject With a TEAE Leading to Withdrawal [n(%)] [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 Death [n(%)]  [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
  
 
 
 
 
 
[1] Percentages are based on the number of subjects in the Safety population in each treatment group. 
[2] Percentages are based on the total number of treatment emergent adverse events reported in each treatment group. 
[3] TEAE that was reported with a relationship of “reasonable possibility”. 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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Table 14.3.1.2 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA Preferred Term 
(Safety Population) 
 
   
   
 
 
 
  SOC 
   MedDRA Preferred Term 
Placebo 
(N=XX) 
Lasmiditan 50 mg 
(N=XX) 
Etc. 
 
 
  
  
 
 
 
 
 
 
 
 
 
 Subjects With At Least One TEAE [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 System Organ Class 1 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 11 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 12 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 13 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 System Organ Class 2 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 21 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 22 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 23 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 
  
 
 
 
 
Note: Each treatment emergent adverse event is counted only once for each subject within each System Organ Class and MedDRA 
Preferred Term. 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar Tables:  
14.3.1.3 
Summary of Serious Adverse Events by System Organ Class and MedDRA Preferred Term (Safety Population) 
 
 


 
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Table 14.3.1.4 
Summary of Treatment Emergent Adverse Events by System Organ Class, MedDRA Preferred Term 
and Maximum Severity 
(Safety Population) 
 
 
  
 
 
 SOC  
MedDRA Preferred Term  
Placebo 
Lasmiditan 
50 mg 
Lasmiditan 
100 mg 
Lasmiditan 
200 mg 
Alprazolam 
1 mg 
Overall 
 
 
 
 
 
 
 
 
 Subjects With At Least One TEAE [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
  
 
 
 
 
 
 
 System Organ Class 1 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
   MedDRA Term 11 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
        Mild [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Moderate [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Severe [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Life-Threatening [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
   MedDRA Term 21 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
   MedDRA Term 22 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
   MedDRA Term 23 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
   Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) xx (xx.x) 
  
 
 
 
 
 
 
 
 System Organ Class 1 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   MedDRA Term 11 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Mild [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Moderate [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Severe [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
        Life-Threatening [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
 
 
 
 


 
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Table 14.3.1.5 
 
Summary of Treatment Emergent Adverse Events by System Organ Class, MedDRA Preferred Term and Relationship 
To Study Drug 
 
(Safety Population) 
 
 
   
   
 
 
 
 
 SOC  
MedDRA Preferred Term 
Placebo 
 Lasmiditan 
50 mg 
Lasmiditan 
100 mg 
Lasmiditan 
200 mg 
Alprazolam 
1 mg 
Overall 
 Subjects With At Least One TEAE [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
 
 System Organ Class 1 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   MedDRA Term 11 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Reasonable Possibility 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     NO Reasonable Possibility 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   MedDRA Term 12 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
 
 System Organ Class 2 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   MedDRA Term 21 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     Reasonable Possibility 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     NO Reasonable Possibility 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   MedDRA Term 22 [n(%)] 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
 
   Etc. 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 Note(s): Each treatment emergent adverse event is counted only once for each subject under the worst 
relationship within each System Organ Class and MedDRA Preferred Term.  
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.2.1 
Listing of Deaths, Other Serious and Significant Adverse Events 
(Safety Population) 
 
Subject 
ID/Gender/
Age 
Day 
Treatment 
AE # 
SOC 
  MedDRA 
Preferred Term 
    Description 
of AE 
Onset Date  
Time 
(Time since 
Last Dose) 
Resolution 
Date Time 
(Duration) 
I: Maximal 
Intensity 
R: Causality 
Assessment 
O: Outcome 
S: Serious AE 
D: AE Lead To 
Discontinuation 
Action Taken With Study 
Treatment / Other 
Action(s) Taken / 
Concomitant Given 
 
 
 
  
  
 
 
 
 
 
xxx 
xxxxx 
xxxxx 
xxxxxxxxxxxx 
  xxxxxxxxxxxx 
     
xxxxxxxxxxxx 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
YYYY-MM-
DD/ 
HH:MM 
(DD:HH:MM) xxxxxx 
xxxxx 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
Similar Tables:  
14.3.2.2  Listing of Adverse Events Leading to Withdrawal 
 
 
 


 
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Table 14.3.4.1 
 
Listing of Abnormal On-Study Laboratory Values 
 
(Safety Population) 
 
 
Category/ 
Parameter (Unit) 
Reference 
Range 
Subject 
ID/Gender/Age 
 
 
Sequence 
Visit 
 
 
Date / Time Value 
Change from 
Baseline 
 
Out-of-Range 
Flag 
Assessment [1] 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Lab Category 1 
 
 
 
 
 
 
 
  
 
  Lab Test 11 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Lab Test 12 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lab Category 2 
 
 
 
 
 
 
 
 
 
 
  Lab Test 21 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Lab Test 22 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] NCS: Not Clinically Significant   /   CS: Clinically Significant   /   RPT: Repeated   /  TBC: To Be Controlled. 
 
Note(s): Abnormal values are determined by applying the reference ranges to the results as reported by the external laboratory analysis. 
 
 
Date: VERSION – YYYY-MM-DD 
 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.4.2 
 
Listing of Clinically Significant On-Study Laboratory Values 
 
(Safety Population) 
 
 
Category/ 
Parameter (Unit) 
Reference 
Range 
Subject 
ID/Gender/Age 
 
 
Sequence 
Visit 
 
 
Date / Time Value 
Change from 
Baseline 
 
Out-of-
Range Flag  Assessment [1] 
 
 
 
 
  
 
 
 
 
 
 
Lab Category 1 
 
 
 
 
 
 
 
  
 
  Lab Test 11 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Lab Test 12 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lab Category 2 
 
 
 
 
 
 
 
 
 
 
  Lab Test 21 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Lab Test 22 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx-xxx 
xxx 
 
xxxxxx 
xxxxxx 
xxx 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] CS: Clinically Significant   /   RPT: Repeated    /    TBC: To Be Controlled 
 
Note(s): Abnormal values are determined by applying the reference ranges to the results as reported by the external laboratory analysis. 
 
 
Date: VERSION – YYYY-MM-DD 
 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 
 
 


 
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Table 14.3.4.3 
Summary of Blood Chemistry 
(Safety Population) 
 
   
 
 
   
 
 
 
 
Parameter (unit) 
Visit Name 
 
Statistic   
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
xxx (xxx) 
Screening 
Value 
N 
xx 
 
 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
Min, Max 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
Day 35 
Value 
N 
xx 
 
 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
Min, Max 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Change from Screening 
N 
xx 
 
 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
Min, Max 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar Tables:  
14.3.4.4  Summary of Hematology 
14.3.4.5  Summary of Quantitative Urinalysis 
 
 


 
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Table 14.3.5.1 
 
Listing of Abnormal On-Study Vital Signs Values 
 
(Safety Population) 
 
 
Assessment (Units) 
Subject 
ID/Gender/Age 
 
Sequence Visit 
Elapsed 
Time 
 
Position Date / Time 
Value 
 
Change from 
Baseline 
Safety Review 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Vital Sign Test 1 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 2 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.5.2 
 
Listing of Clinically Significant On-Study Vital Signs Values 
 
(Safety Population) 
 
 
Assessment (Units) 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
Elapsed 
Time 
 
Position Date / Time 
Value 
 
Change from 
Baseline 
Safety Review 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Vital Sign Test 1 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 2 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx 
 
xxxxxx 
xxxxxx 
xxxxxx 
YYYY-MM-DD:XX:XX 
xxx 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 


 
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Table 14.3.5.3 
Summary of Vital Signs 
(Safety Population) 
 
 
 
 
 
 
 
 
 
 
Parameter (unit) 
 
Visit 
Timepoint 
 
Statistic 
Placebo 
(N=XX) 
Lasmiditan 50 
mg 
(N=XX) 
Etc. 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 1 
 
 
 
 
 
 
 
 
Screening 
 
Value 
N 
 
 
xx 
 
 
 
 
Mean (SD) 
 
 
xx (xx.x) 
 
 
 
 
Median 
 
 
xx.x 
 
 
 
 
Min, Max 
 
 
xx, xx 
 
 
 
 
 
 
 
 
 
Day -1 
 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 
Value 
 
 
 
 
 
 
 
 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
Change 
from 
Baseline 
 
 
 
 
 
 
 
 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAMMING NOTE:  All visits outlined in Appendix A will be included. 
  
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 


 
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Table 14.3.6.1 
 
Listing of Abnormal On-Study ECG Assessments 
 
(Safety Population) 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
 Date / Time 
 Position Safety Review 
Parameter 
(Unit) 
Value 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
xxxxx 
 
xxxxxx 
 YYYY-MM-DD: HH:MM  xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 YYYY-MM-DD: HH:MM  xxxxxx 
xxxxxx 
 
 
 
 
 
 
 YYYY-MM-DD: HH:MM  xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
xxxxx 
 
xxxxxx 
 YYYY-MM-DD: HH:MM  xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
  
 
 
 
 
xxxxx 
 
xxxxxx 
 YYYY-MM-DD: HH:MM  xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.6.2 
 
Listing of Clinically On-Study ECG Assessments 
 
(Safety Population) 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
 
Date / Time 
  
Position 
Safety Review Parameter (Unit) 
Value 
 
 
 
 
 
 
 
 
 
 
 
xxxxx 
 
xxxxxx 
 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
 
xxxxxx 
 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
 
xxxxxx 
 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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Table 14.3.6.3 
Summary of ECG Assessments 
(Safety Population) 
 
 
 
  
 
 
 
 
 
Parameter (unit) 
 
Visit 
 
 
Statistic 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG Assessment Test 1 
 
 
 
 
 
 
 
 
Screening 
Value 
N 
 
 
 
 
 
 
 
Mean (SD) 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
Min, Max 
 
 
 
 
xxx 
 
Value 
 
 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
 
Mean (SD) 
xx (xx.x) 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
Min, Max 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Change from Screening 
 
 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
 
Mean (SD) 
xx (xx.x) 
 
 
 
 
 
 
Median 
xx.x 
 
 
 
 
 
 
Min, Max 
xx, xx 
 
 
 
 
 
 
 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAMMING NOTE:  All visits outlined in Appendix A will be included. 
  
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 


 
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Table 14.3.7.1 
 
Listing of Abnormal On-Study Physical Examination Findings 
 
(Safety Population) 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit  
 
Date / Time 
 Category 
Result (Abnormal Findings) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.7.2 
 
Listing of Clinically Significant On-Study Physical Examination Findings 
 
(Safety Population) 
 
 
Subject ID/Gender/Age 
Sequence 
Visit  
 
Date / Time 
 
Category 
Result (Abnormal Findings) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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APPENDIX C 
PHARMACOKINETIC OUTPUTS SHELLS  
 
 


 
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Project # COL MIG-106  
 
 
 
 
 
 
 
 
 
 
(Page x of y) 
Table 14.2.7.1 
Plasma Concentration by Time Point  
(PK Population) 
 
 
 
 
Lasmiditan 50 mg 
Lasmiditan 100 mg 
Lasmiditan 200 mg 
Time Point 
Statistic 
(N=xx) 
(N=xx) 
(N=xx) 
Predose  N 
xx 
xx 
xx 
Arithmetic Mean 
xx.xxx 
xx.xxx 
xx.xxx 
 
Geometric Mean 
xx.xxx 
xx.xxx 
xx.xxx 
SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 
%CV 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 Median 
xx.xxx 
xx.xxx 
xx.xxx 
 Min, Max 
xx.xxx , xx.xxx 
xx.xxx , xx.xxx 
xx.xxx , xx.xxx 
 
 
 
 
 
Time #2 Postdose  N 
xx 
xx 
xx 
 
Arithmetic Mean 
xx.xxx 
xx.xxx 
xx.xxx 
 
Geometric Mean 
xx.xxx 
xx.xxx 
xx.xxx 
 
SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 
%CV 
xx.xxxx 
xx.xxxx 
xx.xxxx 
 
 Median 
xx.xxx 
xx.xxx 
xx.xxx 
 
 Min, Max 
xx.xxx , xx.xxx 
xx.xxx , xx.xxx 
xx.xxx , xx.xxx 
etc. 
 
 
 
 
 
 
Predose BLQ values were set to 0. 
Standard deviation on the LN scale is approximately equal to CV on raw scale 
Geometric CV%= (Std Dev of ln data)*100 
SAS Program Name:    
 
Date: 
 
 
 
Source Data:  Listing 16.2.5.2 
 
 


 
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Project # COL MIG-106  
 
 
 
 
 
 
 
 
 
 
(Page x of y) 
Table 14.2.7.2 
Correlation of ln(Plasma Drug Levels) to SDLP  
(PK Population) 
 
Lasmiditan 50 mg 
Lasmiditan 100 mg 
Lasmiditan 200 mg 
Statistic 
(N=xx) 
(N=xx) 
(N=xx) 
Spearman Correlation 
0.xxxx 
0.xxxx 
0.xxxx 
Pearson Correlation 
0.xxxx 
0.xxxx 
0.xxxx 
 
 
 
 
Repeat for all correlation output 
 
SAS Program Name:    
 
Date: 
 
 
 
Source Data:  Listings 16.2.5.2 and 16.2.6.X 
 
 


 
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APPENDIX D 
LISTING SHELLS  
 
 


 
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Algorithme Pharma 
 
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Listing 16.2.1 
 
Listing of Study Disposition 
 
 
 
 
Subject ID/Gender/Age 
 
Sequence 
Date of Completion or 
Discontinuation 
Subject 
Status 
Specify 
AE # 
Date of Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.3 
 
Listing of Analysis Populations 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Safety 
Population 
PK 
Population 
 
Intent-to-treat 
Population 
Reason if Excluded from one 
Population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.4.1 
 
Listing of Demographic Characteristics 
 
 
 
 
Subject ID 
 
 
Sequence 
Age 
Date of 
Birth 
Gender Ethnicity 
Race 
Other 
Race  
Weight at Screening 
(kg) 
Height 
(cm) 
BMI at 
Screening 
(kg/m2) 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Algorithme Pharma 
Project # COL MIG-113/CUD-P4-001 
     Page 1 of x 
 
Listing 16.2.4.2 
Listing of Screen Failures 
 
 
Subject ID 
Date 
 
Specify Primary Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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Listing 16.2.5.1 
 
Listing of Investigational Product Administration 
 
 
 
 
 
 
Subject 
ID/Gender/Age 
 
 
Sequence Visit 
Start 
Date/Time 
 
Treatment 
Route 
If Any Dosing Issues, 
Specify 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.5.2 
 
Listing of Lasmiditan Plasma Concentrations 
 
Treatment: 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
 
 
Time Point 
 
 
Date / Time  
Value  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 
 


 
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Project # COL MIG-106/CUD-P8-917 
     Page 1 of x 
 
Listing 16.2.7  
Listing of Adverse Events 
 
 
Subject 
ID/Gender/Age 
Visit 
Treatment 
AE # 
SOC 
  MedDRA 
Preferred Term 
    Description 
of AE 
Onset Date  
Time 
(Time since 
Last Dose) 
Resolution 
Date Time 
(Duration) 
I: Maximal 
Severity 
R: Causality 
Assessment 
O: Outcome 
S: Serious AE 
D: AE Leading To 
Discontinuation 
Action Taken With 
Study Treatment / 
Other Action(s) Taken 
/ Concomitant Given 
 
 
 
  
  
 
 
 
 
 
xxx 
xxxxx 
xxxxx 
xxxxxxxxxxxx 
  xxxxxxxxxxxx 
     
xxxxxxxxxxxx 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
xxxxxx 
xxxxx 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 


 
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Listing 16.2.8.1 
 
Listing of Blood Chemistry 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Lab 
Test 
Name 
(Units) 
Reference 
Range 
Visi
t 
Date 
/ 
Time  
 Value 
Change 
from 
Baseline 
Out-of-
Range Flag 
Assessmen
t [1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] CS: Clinically Significant   /   RPT: Repeated    /    TBC: To Be Controlled 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program 
Source: 
XXXXX.sas 
 
 
Similar listing(s): 
 
L16.2.8.2 
 
Listing of Hematology 
L16.2.8.3 
 
Listing of Urinalysis 
L16.2.8.4 
 
Listing of Urine Drug Screen 
L16.2.8.5 
 
Listing of Pregnancy Test  
 
 
 
 


 
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Listing 16.2.9.1 
 
Listing of Alcohol Habits 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Intake Status 
Quantity 
Frequency 
Start Date End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program 
Source: 
XXXXX.sas 
 
 
 


 
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Listing 16.2.9.2 
 
Listing of Smoking Habits 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Intake Status 
Quantity 
Frequency 
Start Date 
End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program 
Source: 
XXXXX.sas 
 
 
 
 
 


 
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Listing 16.2.9.3 
 
Listing of Prior Medication  
 
 
 
 
Subject 
ID/Gender/
Age 
Sequence 
 
Related 
to 
AE#/MH# 
ATC / 
PT / 
Medicati
on Name 
Indication 
Dose 
(unit) 
Frequency Formulation 
Total 
Daily 
Dose 
Route 
Start 
Date/ 
Time 
End  
Date/ 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar Listing:  
 
Listing 16.2.9.4 Listing of Concomitant Medications 
 
 


 
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Listing 16.2.9.5 
 
Listing of Physical Examination 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit  
 Date / Time  Body System Examined 
Result (Abnormal Findings) 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.6 
 
Listing of Vital Signs  
 
 
 
 
Subject 
ID/Gender/Age 
 
 
Sequence Visit 
 
 
Time 
Point 
 
Position 
Date 
/ 
Time 
Assessment 
(Units)  
Value  
Change 
from 
Baseline 
Safety 
Review  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.7 
 
Listing of ECG Assessments 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence Visit 
Date / Time 
Positio
n 
Safety 
Review 
Parameter 
(Unit) 
 Value 
Change 
from 
Baseline 
 
 
 
 
 
 
 
 
 
 
xxxxx 
 
xxxxxx 
YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
  
 
 
 
 
YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
xxxxx 
 
xxxxxx 
YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
  
 
 
 
 
 
 
 
 
  
 
xxxxx 
 
xxxxxx 
YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 
 
 


 
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Listing 16.2.9.8 
Listing of Screening Summary 
 
 
Subject 
ID/Gender/Age 
Does the subject continue to be eligible? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data 
Source: 
XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.9 
Listing of Medical History 
 
 
Subject 
ID/Gender/Age 
Sequence 
Description of Medical 
History 
Start Date 
End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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CONFIDENTIAL 
 
Project # COL MIG-106/CUD-P8-917 
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Listing 16.2.9.10 
 
Listing of Columbia-Suicide Severity Rating Scale (C-SSRS) 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
Category 
Question 
Answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 


 
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Listing 16.2.9.11 
 
Listing of Epworth Sleepiness Scale 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
Date 
Total Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.12 
 
Listing of Simulator Sickness Questionnaire 
 
 
 
 
Subject 
ID/Gender/Age 
 
Sequence 
Visit 
Date 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 


 
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