A Phase I, Multicenter, Open-Label, Parallel-Group Adaptive Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Renal Function
Phase: PHASE1
Conditions: Migraine
Sponsor: Eli Lilly and Company

Protocol H8H-CD-LAHN (V1) (CUD-P4-001 (COL MIG-113))
A Phase I, Multicenter, Open-Label, Parallel-Group Adaptive Pharmacokinetic 
Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Renal 
Function
NCT03009162 
Approval Date: 6-Jan-2017

 
 
 
A Phase I, Multicenter, Open-Label, Parallel-Group Adaptive Pharmacokinetic Single 
Dose Study of Oral Lasmiditan in Subjects with Normal and Impaired Renal Function 
 
Protocol Number: 
CUD-P4-001 (COL MIG-113) 
Investigational Product: 
Lasmiditan 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
222 Third Street 
Suite 1320 
Cambridge, MA, USA, 02142 
Sponsor’s contact person: 
Tel. 
Cell.
Email. 
 
 
 
Protocol Version 
Date 
1.0 
Original 
2016/12/01 
2.0 
Amendment 01 
2017/01/06 
 
COMPLIANCE 
The study will be conducted in accordance with standards of Good Clinical Practice, as defined 
by the International Conference on Harmonisation and all applicable federal and local 
regulations. 
 
CONFIDENTIALITY STATEMENT 
The information provided in this document is strictly confidential and is available for review to investigator(s) 
and to the appropriate Independent Ethics Committee (IEC) or Institutional Review Board (IRB). It may not be 
used, divulged, published or otherwise disclosed without the written authorization from Algorithme Pharma or 
the sponsor. 
Algorithme Pharma 
Head Office 
575 Armand-Frappier  
Blvd. 
Laval (Quebec) H7V 4B3 
Canada 
www.algopharm.com 
Tel. : (450) 973-6077 
Fax : (450) 973-7866 
PPD
PPD
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TABLE OF CONTENTS 
1. INTRODUCTION .............................................................................................................................................. 14 
1.1. Background ................................................................................................................................................... 14 
1.2. Nonclinical Studies ....................................................................................................................................... 14 
1.3. Pharmacokinetics .......................................................................................................................................... 14 
1.4. Clinical Information ...................................................................................................................................... 15 
1.5. Study Rationale ............................................................................................................................................. 15 
2. STUDY OBJECTIVES ...................................................................................................................................... 15 
2.1. Primary Objective ......................................................................................................................................... 15 
2.2. Secondary Objectives .................................................................................................................................... 15 
3. STUDY DESIGN ................................................................................................................................................ 16 
3.1. General Study Design .................................................................................................................................... 16 
3.2. Number of Centers and Subjects ................................................................................................................... 16 
3.3. Schedule of Drug Administration .................................................................................................................. 16 
4. SUBJECT SELECTION .................................................................................................................................... 17 
4.1. Study Population ........................................................................................................................................... 17 
4.2. Inclusion Criteria ........................................................................................................................................... 17 
4.3. Exclusion Criteria .......................................................................................................................................... 18 
4.4. Withdrawal Criteria ....................................................................................................................................... 21 
5. STUDY TREATMENTS .................................................................................................................................... 22 
5.1. Description and Handling of Study Treatments ............................................................................................ 22 
5.1.1. Formulation of Test Product .................................................................................................................. 22 
5.1.2. Packaging and Labeling ......................................................................................................................... 22 
5.1.3. Storage and Handling ............................................................................................................................. 23 
5.2. Method of Assigning Subjects to Treatment Groups .................................................................................... 23 
5.3. Blinding ......................................................................................................................................................... 23 
5.4. Dosing and Administration ........................................................................................................................... 23 
5.4.1. Dispensing .............................................................................................................................................. 23 
5.4.2. Administration Instructions .................................................................................................................... 23 
5.4.3. Treatment Compliance ........................................................................................................................... 24 
5.4.4. Study Drug Accountability..................................................................................................................... 24 
5.5. Prior and Concomitant Medication ............................................................................................................... 24 
5.6. Study-Specific Restrictions ........................................................................................................................... 26 

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6. STUDY PROCEDURES AND GUIDELINES................................................................................................. 26 
6.1. Study Procedures ........................................................................................................................................... 31 
6.1.1. Physical Examination ............................................................................................................................. 31 
6.1.2. C-SSRS Questionnaire ........................................................................................................................... 31 
6.1.3. Vital Signs .............................................................................................................................................. 31 
6.1.4. Laboratory Evaluations .......................................................................................................................... 31 
6.1.4.1. Pregnancy Tests .............................................................................................................................. 32 
6.1.5. 12-Lead Electrocardiogram .................................................................................................................... 32 
6.1.6. Follow-up Call ....................................................................................................................................... 32 
6.1.7. Pharmacokinetic Sampling ..................................................................................................................... 32 
6.1.7.1. Sample processing, storage and shipping ........................................................................................ 33 
6.2. Bioanalytical Methods ................................................................................................................................... 33 
6.2.1. Aberrant values and retested samples .................................................................................................... 33 
6.2.2. Incurred sample reproducibility ............................................................................................................. 33 
6.3. Pharmacokinetic Measurements .................................................................................................................... 33 
7. ADVERSE EVENTS .......................................................................................................................................... 34 
7.1. Definitions ..................................................................................................................................................... 34 
7.1.1. Severity Assessment ............................................................................................................................... 35 
7.1.2. Causality Assessment ............................................................................................................................. 36 
7.2. Routine Reporting ......................................................................................................................................... 36 
7.3. Serious Adverse Event Reporting ................................................................................................................. 37 
8. STATISTICAL ANALYSIS .............................................................................................................................. 38 
8.1. Analysis Sets ................................................................................................................................................. 38 
8.1.1. Safety Analysis Set ................................................................................................................................ 38 
8.1.2. Pharmacokinetic Analysis Set ................................................................................................................ 38 
8.2. Sample Size Determination ........................................................................................................................... 39 
8.3. Statistical Analysis ........................................................................................................................................ 39 
8.3.1. Descriptive Analysis .............................................................................................................................. 39 
8.3.1.1. Safety Analyses ............................................................................................................................... 39 
8.3.1.2. Pharmacokinetic Endpoint Analyses ............................................................................................... 39 
8.3.2. Statistical Methodology ......................................................................................................................... 39 
8.3.2.1. Interim Analysis .............................................................................................................................. 40 
9. ETHICS ............................................................................................................................................................... 40 
9.1. Institutional Review Board (IRB) ................................................................................................................. 40 
9.2. Ethical Conduct of the Study ......................................................................................................................... 41 

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9.3. Participant Information and Consent ............................................................................................................. 41 
9.4. Subject Confidentiality .................................................................................................................................. 41 
10. DATA COLLECTION, RETENTION, AND MONITORING ...................................................................... 41 
10.1. Case Report Forms ........................................................................................................................................ 41 
10.2. Data Management and Processing ................................................................................................................. 42 
10.3. Quality Assurance ......................................................................................................................................... 42 
10.4. Record Retention ........................................................................................................................................... 42 
10.5. Monitoring of the Study ................................................................................................................................ 42 
11. ADMINISTRATIVE PROCEDURES .............................................................................................................. 42 
11.1. Adherence to Protocol ................................................................................................................................... 42 
11.2. Investigator Responsibilities ......................................................................................................................... 43 
11.3. Delegation of Investigator Duties .................................................................................................................. 43 
11.4. Premature Termination or Suspension of a Study ......................................................................................... 43 
11.5. Clinical Trial Application (CTA) .................................................................................................................. 43 
11.6. Exemption Application for Controlled Substances ....................................................................................... 43 
11.7. Publications ................................................................................................................................................... 43 
12. REFERENCES ................................................................................................................................................... 45 
APPENDIX 01 ........................................................................................................................................................... 46 

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LIST OF IN-TEXT TABLES 
Table 1: Formulation of Lasmiditan, 200 mg Tablets .................................................................. 22 
Table 2. Schedule of Assessments for all subjects ....................................................................... 28 
Table 3. Schedule of Pharmacokinetic Assessments .................................................................... 30 
Table 4. Pharmacokinetic Parameters ........................................................................................... 34 
Table 5. Adverse Event Relationship to Study Drug .................................................................... 36 

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STUDY SYNOPSIS 
Name of Sponsor/Company: 
CoLucid Pharmaceuticals, Inc. 
Name of Product: 
Lasmiditan 
Title of Study: 
A Phase I, Multicenter, Open-Label, Parallel-Group Adaptive 
Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects 
with Normal and Impaired Renal Function 
Study Development Phase: 
Phase I 
Objectives: 
The primary objective of this study is to evaluate the 
pharmacokinetic (PK) profile of lasmiditan following a single oral 
200 mg dose in subjects with impaired renal function relative to 
matched, healthy controls with normal renal function. 
The secondary objective of this study is to assess the safety and 
tolerability of a single oral 200 mg dose of lasmiditan in subjects 
with normal and impaired renal function. 
Test Product: 
Lasmiditan 200 mg tablets 
Dose and Mode of 
Administration: 
Single dose of 200 mg of lasmiditan administered orally. 
Study Design: 
This is a multicenter, open-label, non-randomized, parallel-group, 
adaptive, single dose study.  
This study will enroll up to 32 subjects using an adaptive design 
that can include up to 3 groups of subjects with different degrees of 
renal impairment and one group of control subjects with normal 
renal function. 
First, subjects with severe renal impairment (Group 2) and matched 
subjects with normal renal function (Group 1) will be enrolled. 
There will be 8 subjects in each group. 
Based on safety and PK results from subjects with severe renal 
impairment, Group 3 (Moderate Renal Impairment) and Group 4 
(Mild Renal Impairment) will be enrolled if a substantial change in 
the exposure of lasmiditan is observed in subjects with severe renal 
impairment. There will be 8 subjects in each group. 
All subjects will participate in one treatment period and will receive 
a single dose of lasmiditan in the fasting state.  
Subjects will be confined to the clinic from 10 hours prior to dosing 
until 36 hours after drug administration. 
Duration of Study: 
Up to 38 days, including Screening. 
Study Population: 
Male and female adult subjects with normal renal function and 
male and female adult patients with mild, moderate, and severe 
renal impairment (according to the definition of the National 
Kidney Foundation) using the Modification of Diet in Renal 
Disease (MDRD) classification. 

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Planned Number of Subjects: 
The study is planned to enroll up to 32 subjects: 8 subjects with 
severe renal impairment, 8 subjects with moderate renal 
impairment, 8 subjects with mild renal impairment, and 8 with 
normal renal function. 
Subjects with moderate and mild renal impairment will be enrolled 
as determined by review of safety and PK data from previous 
groups. 
Main Criteria for Inclusion: 
• Male or female aged  ≥ 18 years 
• Body mass index  ≥ 18.50 to < 42.00 kg/m2 
• Negative screening for alcohol and drugs of abuse 
• Non clinically significant findings on 12-lead electrocardiogram 
(ECG) 
• For females, negative result on a pregnancy test 
Group 1 (Normal Renal Function) 
• Presence of normal renal function (eGFR ≥ 90 mL/min/1.73m2) 
• Subjects will be matched by age (±10 years), weight (±20%), 
and gender to the pooled mean values of subjects with the severe 
renal impairment. 
Group 2 (Severe Renal Impairment) 
• Presence of severe renal impairment (eGFR< 30 mL/min/1.73m2) 
Group 3 (Moderate Renal Impairment) 
• Presence of moderate renal impairment (eGFR 30-
59mL/min/1.73m2) 
Group 4 (Mild Renal Impairment) 
• Presence of mild renal impairment (eGFR 60-89 mL/min/1.73m2) 
Renal function for each subject will be determined at the Screening 
Visit, calculated using the MDRD classification. 
Procedures and Assessments 
Safety evaluations including vital signs (body temperature, pulse 
rate and blood pressure), physical exams, safety laboratory tests 
(general biochemistry, hematology, urinalysis, pregnancy test, drug, 
and alcohol screen), ECGs, adverse event (AE) collection, and 
concomitant medication recording will be conducted prior to and 
during the treatment period. 
PK blood samples will be collected at predose and for 36 hours 
after dosing on Day 1; 18 PK blood samples will be obtained from 
each patient/subject. 
PK urine samples will be collected at predose and for 36 hours after 
dosing on Day 1; 6 PK urine samples will be collected postdose 
from urine pooled during specified collection intervals.  
 

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Criteria for Evaluation: 
Safety:  
Safety will be evaluated by assessment of 12-lead safety ECGs, 
measurements of vital signs, physical examination and clinical 
laboratory tests at baseline and at various time points during the 
study, and by the documentation of AEs/concomitant medication. 
Pharmacokinetics: 
The following plasma and urine PK parameters of lasmiditan will 
be calculated: Cmax, Tmax, AUC0-T, AUC0-∞, AUC0-T/∞, λz, Thalf, 
ClTOT/F, VD/F, Ae(0-t), fe, Clr. 
Statistical Analyses: 
Safety data will be listed by subject and summarized by renal 
function group using frequency of event/abnormality or descriptive 
statistical summaries, as appropriate. 
PK parameters will be listed and summarized by group using 
descriptive statistics. Mean and individual plasma concentration-
time profiles will be presented graphically. 
A regression analysis in which the estimated renal function and the 
pharmacokinetic parameters are treated as continuous variables will 
be used to evaluate the relationship between renal function and the 
estimated pharmacokinetic parameters of lasmiditan. If the slope is 
found to be significantly different from zero (p < 0.05), and if more 
than one group of subjects with impaired renal function are 
enrolled, an analysis of variance will be performed to assess the 
difference in the PK parameter between the control and each group 
of subjects with impaired renal function. The 90% confidence 
interval of the difference will be calculated for each comparison. 

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LIST OF ABBREVIATIONS 
Term 
Definition 
AE 
Adverse event 
ANOVA 
Analysis of variance 
AUC 
Area under the curve 
BLQ 
Below the limit of quantification 
Cmax 
Maximum observed concentration 
CNS 
Central Nervous System 
CL 
Clearance 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CV 
Coefficient of variation 
EOI 
End of infusion 
GeoCV% 
Percent geometric coefficient of variation 
GeoMean 
Geometric mean 
λZ 
Apparent terminal elimination rate constant 
IV 
Intravenous 
LLOQ 
Lower limit of quantification 
MDRD 
Modification of Diet in Renal Disease 
MRT∞ 
Mean residence time extrapolated to infinity 
MTD 
Maximum tolerated dose 
Min 
Minimum 
Max 
Maximum 
n 
Number of Observations 
NCA 
Noncompartmental analysis 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
QA 
Quality assurance 
QC 
Quality control 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SEM 
Standard error of the mean 
SOP 
Standard Operating Procedure 
Thalf 
Apparent terminal elimination half-life 
Tmax 
Time to peak concentration 
U.S. 
United States 
 

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FACILITIES 
AUTHOR OF THE PROTOCOL: 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
COORDINATING PRINCIPAL INVESTIGATOR: 
 
  
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone: 
 
PRINCIPAL INVESTIGATOR: 
Maisonneuve-Rosemont 
5415 de l'Assomption Bvl. 
Montreal, Quebec, Canada 
H1T 2M4 
Phone: 
 
SCREENING FACILITY: 
Algorithme Pharma  
1100 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3H5 
CIUSSS de l'est-de-l'île-de-Montréal - installation Hôpital 
Maisonneuve-Rosemont 
5305 de l'Assomption Bvl. 
Montreal, Quebec, Canada 
H1T 2M4 
MEDICAL LABORATORY*: 
Dynacare Solutions Santé 
4850 Dobrin St. 
Montreal, Quebec, Canada 
H4R 2P8 
*Samples may be outsourced to affiliated accredited laboratory facilities, if necessary. 
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BIOANALYTICAL FACILITY: 
Covance Laboratories 
3301 Kinsman Blvd, 
Madison, WI 53704, USA  
 
SCIENTIFIC AND REGULATORY FACILITY: 
Algorithme Pharma  
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
PROJECT MANAGEMENT: 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
STATISTICAL FACILITY: 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
DATA MANAGEMENT FACILITY:
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
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1.
INTRODUCTION
1.1. Background 
CoLucid Pharmaceuticals, Inc. (CoLucid) is developing lasmiditan (COL-144), a small molecule 
5-HT1F receptor agonist. The chemical name of lasmiditan (COL-144) is 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. 
1.2. Nonclinical Studies 
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. Unlike triptans, lasmiditan
did not constrict rabbit saphenous vein, an assay predictive of human coronary artery
constriction. Lasmiditan is under development as a neurally acting treatment for migraine
without the vasoconstrictor liability of triptans.
Safety pharmacology studies (central nervous system [CNS] respiratory, cardiovascular, and 
renal) employing single intravenous (IV) administration of lasmiditan indicated that 
administration of lasmiditan at the intended clinically effective exposure levels is unlikely to 
produce adverse effects on cardiovascular, respiratory or renal function. Based on observations 
in mice, the neural mechanism of action of lasmiditan may, with exposure to high doses, produce 
CNS effects such as increased sensitivity to auditory stimuli, analgesia, reduced activity, 
hypothermia, and anticonvulsant activity. However, there have been no comparable observations 
in clinical studies, apart from alleviation of headache pain. 
1.3. Pharmacokinetics 
Cmax and AUC for subjects dosed orally (200 mg) were also measured in a fed/fasted study (COL 
MIG-104). During fed conditions (394.7 ng/mL and 2244 ng*h/mL, respectively) PK parameters 
were slightly increased compared to the fasted condition (322.8 ng/mL and 1892 ng*h/mL, 
respectively). Hence, food had a minor effect on the PK of lasmiditan. 
The plasma clearance (~59 L/h IV and 160 L/h oral), and the high total volume of distribution 
(~300 L for IV and 1016 L for oral), indicated extensive distribution. There were no significant 
effects of gender or body weight on PK parameters. 
In vitro and in vivo metabolism studies have shown that the metabolic pathways of lasmiditan 
include N-oxidation, N-dealkylation, carbonyl oxidation, desaturation of the piperidine moiety, 
ketoreduction, or a combination of each. Up to 12 metabolites have been detected in human 
hepatocytes, of which none were unique to human. When examined in vivo using LC-MS/MS 

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analysis of human plasma samples from subjects receiving oral lasmiditan, three major 
metabolites (M7, M8, and (S,R)-M18) were detected. The relative proportions of metabolites to 
intact lasmiditan remained reasonably constant throughout the oral dose range studied and their 
PK were approximately linear. 
The half-life of the metabolites fell into two categories; the non-reduced metabolites with a half-
life similar to or only slightly longer than intact lasmiditan (~4.5 h), and the reduced metabolites 
with a half-life distinctly longer (>12 h) than that of lasmiditan. 
1.4. Clinical Information 
Five Phase 1 studies of lasmiditan have been completed in Europe using IV, sublingual, and oral 
formulations of lasmiditan in 213 healthy subjects. Two European Phase 2 studies have been 
completed with lasmiditan in the acute treatment of migraine. COL MIG-301 (SAMURAI) the 
first of two, Phase 3 randomized, double-blind, placebo controlled trials has completed in the 
United States. The second confirmatory study, COL MIG-302 (SPARTAN), is ongoing in the 
US, UK and Germany along with COL MIG-305, the open-label year long dosing study. 
Further information on the lasmiditan formulation, animal studies, and human studies can be 
found in the current Investigator’s Brochure. 
1.5. Study Rationale 
Lasmiditan is excreted through the kidneys. This study was designed to evaluate the effects of 
impaired renal function on lasmiditan PK parameters, and on its safety. This study will employ a 
targeted, reduced PK study design in which subjects enrolled will have severe renal impairment 
with a screening estimated eGFR < 30 mL/min/1.73m2. Data from these subjects will be 
compared to matched subjects with normal renal function (eGFR ≥ 90 mL/min/1.73m2). This 
approach is consistent with recommendations in the FDA Guidance for Industry entitled 
“Pharmacokinetics in Patients with Impaired Renal Function-Study Design, Data Analysis, and 
Impact on Dosing and Labeling”. Should substantial changes in exposure be observed, additional 
groups including subjects with lesser degrees of renal impairment will be enrolled.  
Results of this study may inform on lasmiditan dosing recommendation in patients with renal 
impairment. 
2. STUDY OBJECTIVES 
2.1. Primary Objective 
The primary objective of this study is to evaluate the pharmacokinetic profile of lasmiditan 
following a single oral 200 mg dose in subjects with impaired renal function relative to matched, 
healthy controls with normal renal function. 
2.2. Secondary Objectives 
The secondary objective of this study is to assess the safety and tolerability of a single oral 
200 mg dose of lasmiditan in subjects with normal and impaired renal function. 

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3. STUDY DESIGN 
3.1. General Study Design 
This is a multi-center, open-label, non-randomized, parallel-group, adaptive, single dose study.  
This study will enroll up to 32 subjects using an adaptive design that can include up to 3 groups 
of 8 subjects with different degree of renal impairment and one group of 8 control subjects with 
normal renal function. 
Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion 
criteria and none of the exclusion criteria will be entered in the study. 
First, approximately 16 subjects will be enrolled with severe renal impairment and matched 
subjects with normal renal function. There will be 8 subjects in each of the following groups 
based on renal function at screening: 
• Group 1: Healthy subjects with normal renal function (eGFR ≥ 90 mL/min/1.73m2) 
• Group 2: Severe renal impairment subjects (eGFR < 30 mL/min/1.73m2) 
Based on safety and PK results from subjects with severe renal impairment (Group 2), Group 3 
(Moderate Renal Impairment) and Group 4 (Mild Renal Impairment) will be enrolled if 
substantial change in the exposure of lasmiditan is observed in subjects with severe renal 
impairment. There will be 8 subjects in each of the following groups based on renal function at 
screening: 
• Group 3: Moderate renal impairment subjects (eGFR 30-59 mL/min/1.73m2) 
• Group 4: Mild renal impairment subjects (eGFR 60-89 mL/min/1.73m2) 
All subjects will participate in one treatment period and will receive a single dose of lasmiditan 
in the fasting state.  
Subjects will be confined to the clinic from 10 hours prior to dosing until 36 hours after drug 
administration. 
The total duration of each subject’s participation in the study will be 3 days (Day –1 through the 
last PK sample taken on Day 2), not including the screening and follow-up phone call. 
3.2. Number of Centers and Subjects 
The study is planned to enroll up to 32 subjects in 2 centers. Eight subjects will be enrolled in 
each group. Subjects who withdraw from the study may be replaced. Replacement subjects will 
be not enrolled for subjects who discontinue the study due to treatment-related AEs. 
An effort will be made to include subjects with high BMI, moreover, an effort will be made to 
enroll more females than males (for an approximate ratio of 60%/40%) or at least 50%/50%. 
3.3. Schedule of Drug Administration 
The following treatment regimen will be used: 

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• Experimental treatment: Lasmiditan 200 mg 
The total duration of the study is expected to be 35 days, including the screening. 
The study may be stopped or interrupted at any time for safety, PK, or administrative reasons. 
4. SUBJECT SELECTION 
4.1. Study Population 
Subjects who meet all the inclusion criteria and none of the exclusion criteria will be eligible for 
participation in this study. A signed copy of the informed consent form will be provided to each 
subject. 
4.2. Inclusion Criteria 
All subjects: 
1. Availability for the entire study period 
2. Motivated volunteer and absence of intellectual problems likely to limit the validity of 
consent to participate in the study or the compliance with protocol requirements; ability 
to cooperate adequately; ability to understand and observe the instructions of the 
physician or designee 
3. Male or female volunteer 
4. A female volunteer must meet one of the following criteria: 
- 
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: 
• Abstinence from heterosexual intercourse 
• Systemic contraceptives (birth control pills, injectable/implant/insertable 
hormonal birth control products, transdermal patch) 
• Intrauterine device (with or without hormones) 
• Condom with spermicide or condom with intra-vaginally applied spermicide 
- 
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) 
5. A male volunteer with sexual partners who are pregnant, possibly pregnant, or who could 
become pregnant must meet the following criteria: 

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- 
Participant is unable to procreate, defined as surgically sterile (i.e. has undergone a 
vasectomy within at least the last 6 months) 
- 
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: 
• Abstinence from heterosexual intercourse. 
• Condom with spermicide or condom with intra-vaginally applied spermicide 
6. A male volunteer agrees to refrain from sperm donation from drug administration until 
3 months after the drug administration 
7. Volunteer aged of at least 18 years 
8. Volunteer with a body mass index (BMI) ≥18.50 kg/m2 and < 42.00 kg/m2 
9. Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes 
or less per day for at least 3 months before Day 1 of this study. An ex-smoker is defined 
as someone who completely stopped smoking for at least 6 months before Day 1 of this 
study 
10. Willingness to adhere to the protocol requirements as evidenced by the informed consent 
form (ICF) duly read, signed and dated by the volunteer 
Subjects with Normal Renal Function: 
11. Clinical laboratory values within the laboratory's stated normal range; if not within this 
range, these must be without any clinical significance 
12. Have no clinically significant diseases captured in the medical history or evidence of 
clinically significant findings on physical examination and/or clinical laboratory 
evaluations (hematology, general biochemistry, electrocardiogram [ECG], and urinalysis) 
13. For each gender, have to match by age (± 10 years) and weight (± 20%) to the pooled 
mean values of subjects with severe renal impairment 
14. Have an eGFR ≥ 90 mL/min/1.73m2 calculated using MDRD equation at screening 
Renal Impaired Subjects: 
15. Considered clinically stable in the opinion of the Investigator 
16. Presence of mild renal impairment (eGFR 60-89 mL/min/1.73m2), moderate renal 
impairment (eGFR 30-59 mL/min/1.73m2), or severe renal impairment (eGFR < 30 
mL/min/1.73m2) calculated using MDRD equation at screening 
4.3. Exclusion Criteria 
All Subjects: 
1. Females who are pregnant or are lactating 

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2. History of significant hypersensitivity to lasmiditan or any related products (including 
excipients of the formulations) as well as severe hypersensitivity reactions (like 
angioedema) to any drugs  
3. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically 
relevant psychiatric diseases 
4. Subject is at imminent risk of suicide (positive response to question 4 or 5 on the C-
SSRS) or had a suicide attempt within 6 months prior to the screening visit 
5. Presence or history of any disorder (including Parkinson disease) that could interfere with 
completion of the study based on the opinion of the Principal Investigator 
6. Any history of tuberculosis and/or prophylaxis for tuberculosis 
7. Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) 
(hepatitis B)) or Hepatitis C Virus (HCV (C)) tests 
8. Maintenance therapy with any drug or significant history of drug dependency or alcohol 
abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) 
9. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 
(CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, 
fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP 
enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and 
St John’s Wort), in the previous 28 days before Day 1 of this study 
10. Females who are pregnant according to a positive pregnancy test 
11. Volunteers who took lasmiditan in the previous 28 days before Day 1 of this study 
12. Volunteers who took an Investigational Product (in another clinical trial) in the previous 
28 days before Day 1 of this study 
13. Volunteers who have already participated in this clinical study 
14. Volunteers who donated 50 mL or more of blood in the previous 28 days before Day 1 of 
this study 
15. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical 
studies, etc.) in the previous 56 days before Day 1 of this study 
Subjects with Normal Renal Function: 
16. Seated pulse rate less than or equal 40 Beats per Minute (bpm) or more than 100 bpm at 
screening 
17. Seated blood pressure below 90/60 mmHg or higher than 140/90 mmHg at screening 
18. Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions 
known to interfere with the absorption, distribution, metabolism, or excretion of drugs or 
known to potentiate or predispose to undesired effects 

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19. History of significant gastrointestinal, liver or kidney disease that may affect drug 
bioavailability, including but not limited to cholecystectomy 
20. Presence of significant cardiovascular, pulmonary, hematologic, neurological, 
psychiatric, endocrine, immunologic or dermatologic disease 
21. Presence of out-of-range cardiac interval (PR < 110 msec, PR > 220 msec, QRS < 
60 msec, QRS >119 msec and QTc > 450 msec for males and > 460 msec for females) on 
the screening ECG or other clinically significant ECG abnormalities 
22. Positive screening of alcohol and/or drugs of abuse 
23. Any clinically significant illness in the previous 28 days before Day 1 of this study 
Renal Impaired Subjects: 
24. Seated pulse rate less than 50 bpm or more than 110 bpm at screening 
25. Seated blood pressure below 90/50 mmHg or higher than 180/110 mmHg at screening 
26. Currently undergoing any method of dialysis 
27. History of renal transplant 
28. History or presence, in the opinion of the Investigator, of significant clinically unstable 
respiratory, cardiovascular, pulmonary, hepatic, hematologic, gastrointestinal, endocrine, 
immunologic, dermatologic, neurologic, or psychiatric disease,  
29. Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c > 10% 
30. Require immunosuppressive medications for treatment of immune-mediated renal disease 
or kidney transplant recipients 
31. Evidence of renal carcinoma present at the time of screening 
32. Have relevant clinical laboratory abnormalities, including any elevation of alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin at screening. If 
the investigator concludes that there is no safety risk for subjects with isolated laboratory 
abnormalities (eg, those that do not reflect end-organ dysfunction; for example, elevated 
bilirubin in Gilbert’s subjects) to participate in the study, such cases need to be discussed 
and approved by the sponsor’s medical monitor prior to study enrollment 
33. Presence of clinically significant physical, laboratory, or ECG finding that, in the opinion 
of the Investigator and/or sponsor, may interfere with any aspect of study conduct or 
interpretation of results 
34. Subjects with acute, unstable, or untreated significant medical conditions. Subjects 
requiring treatment for renal impairment or other chronic disease (eg, well-controlled 
diabetes, hypertension) must be on a stable treatment plan (medicines, doses, and 
regimens) for at least 2 weeks (except insulin) prior to Day 1 and during the entire study.  
Small adjustments in the dosages of some concomitant medications may be permitted 
during the study, and will be discussed on a case-by-case basis.  In all cases, the subjects’ 

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treatment history must be reviewed and their enrollment must be agreed to by both the 
investigator and the sponsor’s medical monitor 
35. Positive screening of alcohol and/or drugs of abuse unless results can be explained by a 
prescription medication 
36. Concurrent use of medications known to affect the elimination of serum creatinine (eg, 
trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors 
of renal tubular secretion (eg, probenecid) within 30 days prior to the first dose of study 
drug or anticipated need for these therapies through the last PK sample 
4.4. Withdrawal Criteria 
Subjects may voluntarily withdraw from the study, or be removed from the study at the 
discretion of the Investigator or sponsor at any time. The Investigator may withdraw a subject at 
any time if it is determined that continuing the study would result in a significant safety risk to 
the subject. 
If such withdrawal occurs, or if the subject fails to return for visits, the Investigator should 
determine the primary reason for a subject’s premature withdrawal from the study and record the 
reason in the respective subject’s study documents. Attempts should be made to have the subject 
complete the Post-Study tests or Early Termination study procedures.  
Premature withdrawal may occur for any of the following reasons: 
• A subject who experiences emesis within 5 hours following drug administration will be 
removed from the study period. 
• Noncompliance with the protocol requirements 
• Difficulties with blood collection 
• Pregnancy 
• AE 
• Subject request 
• Investigator request 
• Sponsor request 
• Unanticipated event that could result in an inadequately characterized pharmacokinetic 
profile, such as a missed blood draw, an AE, meal deviations or concomitant 
medications. 
• Subjects who are prematurely withdrawn from the study for reasons other than safety 
may be replaced by an equal number of newly enrolled subjects at the sponsor’s 
discretion. 

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5.
STUDY TREATMENTS
5.1. Description and Handling of Study Treatments 
5.1.1. Formulation of Test Product 
Lasmiditan is a new formulation of 
, which are 5-HT1F receptor agonists, developed by 
CoLucid Pharmaceuticals, Inc. for oral administration of the acute treatment of migraine. Oral 
doses of lasmiditan 50 mg, 100 mg and 200 mg are being investigated in Phase 3 clinical trials. 
Lasmiditan is available in a 200 mg tablets. The Test product used in this study will be provided 
by the sponsor. See Table 1 for the formulation of lasmiditan. 
Table 1: Formulation of Lasmiditan, 200 mg Tablets 
Component 
Function 
Amount 
200mg Tablet 
Intragranular Components 
Lasmiditan hemisuccinate 
a, b
Active 
Ingredient 
231.28 mg 
Microcrystalline cellulose 
PH102 b 
Filler 
123.47 mg 
Starch 1500 
Binder 
30.0 mg 
Croscarmellose sodium 
Disintegrant 
22.5 mg 
Sodium lauryl sulfate 
Wetting Agent 
2.25 mg 
Purified water c 
Granulating 
Medium 
Qs 
Extragranular Components 
Croscarmellose sodium 
Disintegrant 
31.5 mg 
Magnesium stearate 
(Non-bovine) 
Lubricant 
9.0 mg 
Totals 
450 mg 
Film Coating Materials 
Opadry II White 
(85F18422) d 
Film Coat 
11.25 mg 
Purified water e 
Suspending 
Agent 
(45.00 mg) 
 a 
A salt correction factor for the hemisuccinate is assigned as 0.865 
b
Note that the amount of lasmiditan hemisuccinate may be adjusted for purity and moisture content.  An 
adjustment will be made to the amount of microcrystalline cellulose used to maintain tablet weight. 
c
Water for granulation is removed upon drying of the wet mass. 
d
Opadry II White (85F18422) is prepared as a suspension at 20% w/w in Sterile Water for Injection and 
applied to a target of 2.5% weight gain. 
e 
The amount of water may be adjusted to facilitate suspension of the coating agent.  This water is removed 
during processing and does not appear in the final product. 
5.1.2. Packaging and Labeling 
The sponsor will be responsible for ensuring that the treatment is manufactured in accordance 
with applicable Good Manufacturing Practice regulations and requirements. All labels for study 
CCI

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drugs will meet applicable requirements of the protocol and the Canadian Health Products and 
Food Branch. 
5.1.3. Storage and Handling 
Lasmiditan tablets should be stored by the study site at controlled room temperature of 25°C 
(77°F); excursions are permitted to 15°C (59°F). 
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures. 
5.2. Method of Assigning Subjects to Treatment Groups 
No randomization will be performed for this study. Instead subjects will be categorized into 
either the control group of healthy volunteers with normal renal function, or into one of the three 
groups of subjects with varying degrees of renal impairment. 
Once a subject number has been assigned to a subject, it will not be reassigned to another 
subject. Subjects who withdraw from the study may be replaced. Replacement subjects will not 
be enrolled for subjects who discontinue the study due to treatment-related toxicity. A new 
unique subject number will be assigned to the replacement subject. 
5.3. Blinding 
No unblinding procedure is required, as this is an open-label study. 
5.4. Dosing and Administration 
5.4.1. Dispensing 
Designated site staff will dispense study drug in tablet form. 
Study drugs will be administered to the subjects under supervision of the study center personnel. 
5.4.2. Administration Instructions 
Study drug will be administered orally in the morning.  
Dosing will be performed by trained personnel and supervised by the Principal Investigator or 
physician in charge. Adequate time intervals between subjects will be observed to ensure timely 
blood sampling. 
Subjects will be asked to fast overnight (no food or drink, except water) prior to each dosing, for 
a minimum of 10 hours, at Day -1. Fasting will continue for at least 4 hours following drug 
administration, after which a standardized lunch will be served. A supper, a light snack and other 
meals will also be served at appropriate times thereafter, but not before 9 hours after dosing. 
Fluid intake other than water will be controlled for housing period and for all subjects. Water 
will be provided ad libitum until 1 hour pre-dose. The drug will be given with about 240 mL 
(8 oz.) of water at room temperature. Water will be allowed ad libitum beginning 1 hour after the 
administration of the drug. 

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The tablet must be swallowed whole and must not be chewed or broken. 
Study medications will be administered to each subject consecutively for the purpose of accurate 
sampling time. The date and time of each dose must be recorded. 
The physician in charge will remain at the clinical site for at least the first 4 hours following drug 
administration, and will remain available at all times during the study. 
5.4.3. Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of the Investigator (or designee). 
• A mouth and hand check of all subjects will be carried out to ensure that all tablets have 
been swallowed. 
5.4.4. Study Drug Accountability 
Complete and accurate records of all study drugs must be kept. This includes acknowledgment of 
receipt of each shipment of study product (quantity and condition), subject dispensing records, 
and returned or destroyed study product. 
At the conclusion of the study, all unused investigational products and all medication containers 
will be returned to the sponsor unless the sponsor has approved other arrangements. Drug 
accountability will be performed at the completion of the trial. 
5.5. Prior and Concomitant Medication 
Renal-impaired subjects will be permitted to continue taking any prescription or OTC medication 
necessary for the management of their renal disease or other concurrent illness. The dosing 
schedules must be stable for 2 weeks (except insulin) before Day 1 of the study and maintained 
throughout the study. Minor dose changes consistent with treatment practices may be permitted 
at the discretion of the Investigator. All medications taken during the 14 days prior to dosing will 
be recorded in the subject’s CRF and reviewed by the Investigator. When concomitant 
medications are administered, the indication, name, dose, route, and frequency will be recorded 
in each subject’s CRF. 
For healthy subjects, beside enzyme-modifying drugs that are not allowed for 28 days (refer to 
exclusion criteria), subjects will be requested to abstain from taking any prescription medications 
used with the intention to treat a condition for 28 days prior to the first dosing and during the 
study, unless judged differently by the Principal Investigator or designee. Systemic 
contraceptives and hormone replacement therapy will be permitted. Subjects will also be 
requested to abstain from taking any over-the-counter (OTC) products for 7 days prior to the first 
dosing and during the study. They will be specifically reminded that this includes cold 
preparations (containing ASA), acetylsalicylic acid (ASA), vitamins and natural products used 
for therapeutic benefits and antacid preparations. Vitamins used as nutritional supplements in 
non-therapeutic doses (as judged by the Principal  Investigator or designee) may be accepted, but 
they must be stopped at least 48 hours prior to the first dosing and during the study. 

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If a medication (including OTC) other than those specified in the protocol is used after the first 
drug administration or at any time before the end of the study, the Principal Investigator or 
designee and/or the sponsor will decide whether the subject will be permitted to remain in the 
study, depending on the drug used, the time of drug intake, etc. The drug and dose will be noted. 

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5.6. Study-Specific Restrictions 
• Subjects will be requested to abstain from alcohol for 48 hours prior to dosing and during 
study period. Throughout the study (including the return visits), in case of any doubt 
about alcohol consumption, a test for alcohol may be performed to confirm the 
physician's judgment. 
• During the study, subjects who are light-smokers should not smoke more than 
10 cigarettes per day. They will also be instructed to abstain from smoking for 2 hours 
prior to and until 4 hours after drug administration at study period. 
• Subjects will be requested to avoid food or beverages containing xanthines (i.e. tea, 
coffee, cola drinks, energy drinks or chocolate) for 48 hours prior to dosing and during 
study period. 
• Subjects will be instructed to avoid food or beverages containing grapefruit and/or 
pomelo for 7 days prior to dosing and during study period. 
• Subjects will remain seated for the first 4 hours following drug administration, avoiding 
both vigorous exertion and complete rest. However, should AEs occur at any time, 
subjects may be placed in an appropriate position. Subjects will not engage in strenuous 
activity at any time during the confinement. 
• Female volunteers of childbearing potential will have to take appropriate measures to 
prevent pregnancy for at least 28 days prior to the administration of the study drug, 
during the study and for at least 60 days after the drug administration, as described in 
Section 4.2. 
• Male subjects who are apt to procreate will be expected to use an acceptable 
contraceptive regimen from Day 1 of this study, throughout the duration of the entire 
study, and until at least 3 months after the drug administration, as described in Section 
4.2. Condoms with spermicide will be provided to subjects upon departure from the 
clinical site. In addition to the use of condoms with spermicide, subjects will be informed 
that it is strongly recommended that their female partner uses one of the two methods 
listed below: 
- 
Systemic contraceptives (birth control pills, injectable/ implantable/ insertable 
hormonal birth control products, transdermal patch). 
- 
Intrauterine device. 
• Male subjects must refrain from sperm donation from the screening and until at least 
3 months after the drug administration. 
6. STUDY PROCEDURES AND GUIDELINES 
Unless otherwise stated in this protocol, clinical site standard operating procedures (SOPs), 
which are available for all activities relevant to the quality of the study, will be followed during 
this study. The different parts of this study are summarized in Table 2 and explained in the 
following sections. The list of assessments for each study parts are indicated with an "X" when 

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the assessments have to be performed. Any deviation from protocol procedures should be noted 
in the CRFs and the sponsor should be notified. 

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Table 2. Schedule of Assessments for all subjects 
Examination 
Screening 
Days 
Post-
Study 
Tests or 
ETa 
End of Study 
Day 28 to – 1 
-1 
1 
2 
2 
7 (±3) 
Review Inc/Exclusion Criteria & Medical 
History 
X 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Check-in 
 
X 
 
 
 
 
Dosing 
 
 
X 
 
 
 
Clinic Confinement 
 
X 
X 
X 
 
 
Discharge 
 
 
 
X 
 
 
Demographics 
X 
 
 
 
 
 
C-SSRS questionnaire 
X 
 
 
 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
 
X 
 
Vital Signs 
X 
 
Xb 
 
X 
 
Height, Weight, and BMI 
X 
 
 
 
 
 
12-lead ECG 
X 
Xc 
Xc 
 
X 
 
HIV Ag/Ab Combo, HBsAg (B) (Hepatitis 
B) and HCV (C) Tests 
X 
 
 
 
 
 
Drug and Alcohol Screen 
X 
X 
 
 
 
 
Pregnancy test (females) 
X 
X 
 
 
X 
 
Clinical Laboratory Evaluations 
X 
Xd 
 
 
X 
 
PK Blood Samplese 
 
 
X 
X 
 
 
Urine PK Collectione 
 
 
X 
X 
 
 
Follow-up Call 
 
 
 
 
 
X 
AEs Recording 
X 
X 
X 
X 
X 
 

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a Early Termination (ET).  
b Vital signs will be measured prior to dosing and approximately 2 and 4 hours after study drug administration. 
c 12-lead ECG will be performed prior to dosing and approximately 2 hours after study drug administration. 
d Clinical laboratory tests (hematology, biochemistry, and urinalysis) will be performed in the evening prior to drug administration.  
e PK blood and urine samples will be collected according to schedule of PK assessments in Table 4. 
 

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Table 3. Schedule of Pharmacokinetic Assessments 
PK Blood Sampling 
Urine PK Collection Intervals 
Prior to dosing 
Prior to dosing  
0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 
and 36 hours postdose 
0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 hours postdose 
 
 
Time of PK sampling and dosing must be recorded. 
 
 

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6.1. Study Procedures 
Safety assessments will include physical examination, vital signs (blood pressure, heart rate, and 
body temperature), 12-lead ECG, laboratory tests (hematology, biochemistry, and urinalysis), 
and continuous AE monitoring. Body weight and height will be measured at Screening. 
Clinically significant physical examination findings prior to the administration of study drug will 
be recorded as a medical history; clinically significant findings after the drug administration will 
be recorded as an AE. 
The laboratory tests will be carried out according to the standard operating procedures of the 
licensed medical laboratory. Abnormal results will be verified to rule out laboratory error. 
Persistent relevant abnormal values should be followed up until the cause is determined or until 
the values return to the pre-medication value. 
After the ICF is signed, information about all local and systemic clinical events, whether 
volunteered by the subject, discovered by Investigator questioning, or detected through other 
means, will be collected, recorded and followed as appropriate. 
6.1.1. Physical Examination 
A complete physical examination will be performed by a medically qualified and licensed 
individual as scheduled in Table 2. The physical examination will include a review of the 
following: head and neck, heart, lungs, abdomen and general appearance. 
Demographic data (age, gender, race, body weight adjusted for indoor clothing, height, BMI), 
and alcohol and smoking habits will be recorded. 
During study days, not requiring a complete physical examination, a symptom-targeted physical 
exam should be done if a new AE is reported, if medically indicated. 
6.1.2. C-SSRS Questionnaire 
A Columbia Suicide Severity Rating Scale will be performed as scheduled in Table 2. 
6.1.3. Vital Signs 
Vital sign measurements (body temperature, pulse rate, blood pressure and orthostatic blood 
pressure) are specified in Table 2. Vital signs can also be monitored during the study when 
judged necessary by the physician in charge or designee. Vital signs are to be performed prior to 
blood draws. 
6.1.4. Laboratory Evaluations 
Laboratory evaluations will be performed as scheduled in Table 2. The physician in charge or 
designee will assess each abnormal value to determine if it is clinically significant. Postdose 
clinically significant laboratory values will be reported as AEs. 

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•
General biochemistry: Sodium, potassium, chloride, glucose, blood urea nitrogen (BUN),
creatinine, eGFR, total bilirubin, alkaline phosphatase, AST, ALT and albumin
•
Hematology: White cell count with differential (absolute values of neutrophil,
lymphocyte, monocyte, eosinophil, and basophil), red cell count, hemoglobin,
hemoglobin A1c, hematocrit, mean corpuscular volume (MCV), and platelets count
•
Urinalysis: Color, appearance, specific gravity, pH, leukocyte, protein, glucose, ketones,
bilirubin, blood, nitrite, urobilinogen. Microscopic examination will only be performed if
the dipstick test is outside of the reference range for leukocyte, blood, nitrite or protein
•
Serology: HIV Ag/Ab Combo, HBsAg and HCV
•
Drug Screen: Alcohol, amphetamines, barbiturates, cannabinoids (THC), cocaine, opiates
and phencyclidine (PCP)
6.1.4.1. 
Pregnancy Tests 
A pregnancy test will be performed on female subjects as specified in Table 2. 
6.1.5. 12-Lead Electrocardiogram 
Twelve-lead ECGs will be performed as specified in Table 2. On study days ECGs are 
conducted, they should be scheduled prior to blood draws that occur for that day, as the blood 
draws can impact the ECG reading. Subjects must be in a supine position for 10 minutes prior to 
ECG. 
6.1.6. Follow-up Call 
A symptom-directed follow-up telephone call will be made to all subjects following drug 
administration as specified in Table 2. 
6.1.7. Pharmacokinetic Sampling 
Blood samples will be collected by direct venipuncture. However, as an option to the volunteer 
or if judged necessary by the clinical staff, blood samples may be collected from an indwelling 
cannula (stylet catheter that requires no flushing), which will be placed in the forearm vein of the 
subject. Blood samples will be kept in an ice-water bath pending processing. Blood samples will 
be collected in one tube of 6 mL each. 
The complete schedule for each part is presented in Table 3. The time of blood sample collection 
will be calculated according to the drug administration schedule. The clock time of all blood 
draws will be recorded and reported for all subjects in the CRF. For postdose samples, all 
deviations from the scheduled sampling time of 2 minutes or more will be reported in the final 
report. 
The total volume of blood withdrawn, including ~21 mL required for screening, on-study and 
poststudy tests, should not exceed 129 mL per subject. 
During the study, a baseline urine sample will be collected before drug administration. After 
dosing, urine samples will be collected over 36 hours over 6 collection intervals (Table 3). The 

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total volume of urine collected at each interval will be measured and two containers (~ 5 mL 
each) will be preserved. 
6.1.7.1. 
Sample processing, storage and shipping 
Blood samples will be processed, split, stored, and shipped according to the sample processing 
instructions supplied by the bioanalytical facility. 
Urine samples will be processed, split, stored, and shipped according to the sample processing 
instructions supplied by the bioanalytical facility. 
6.2. Bioanalytical Methods 
Plasma and urine lasmiditan concentrations will be measured according to validated 
bioanalytical methods.  
Samples from all subjects who received the investigational product will be assayed. 
6.2.1. Aberrant values and retested samples 
Unacceptable values attributable to bioanalytical reasons will be determined according to the 
bioanalytical Facility’s SOPs. Such re-assayed samples will be termed “repeats”. The method of 
re-assay and the acceptance criteria for selecting which value to report for the re-assayed samples 
will follow the bioanalytical Facility’s SOPs. All cases of re-assay will be reported in the final 
report. 
No samples will be repeated for pharmacokinetic reasons. 
6.2.2. Incurred sample reproducibility 
In order to establish the reproducibility of the assay with incurred samples, at least 10% of the 
total analyzable study samples will be selected and re-assayed. The replicate measurement is not 
to be averaged with the original one, but both values will be presented in the bioanalytical report 
with the initial value being used for PK calculations. The concentrations of the original and 
replicate samples will be tabulated, along with the percent difference between the two values. 
6.3. Pharmacokinetic Measurements 
The PK parameters are presented in Table 4. Below limit of quantitation concentrations (coded 
BLQ) will be treated as zero for all PK analyses. All reported sampling time deviations (see 
Section 6.1.7) will be taken into consideration for evaluation of plasma PK parameters. 
The pharmacokinetic parameters will be estimated using a non-compartmental approach with a 
log-linear terminal phase assumption. The trapezoidal rule will be used to estimate the area under 
the curve, and the terminal phase will be estimated by maximizing the coefficient of 
determination estimated from the log-linear regression model. Disposition parameters (AUC0-∞, 
AUC0-T/∞, λZ, Thalf, ClTOT/F and VD/F) will not be estimated for individual concentration-time 
profiles where the terminal log-linear phase cannot be reliably characterized. 
In the case where less than 3 consecutive measurable plasma concentrations of lasmiditan is 
observed, the AUC parameters will not be estimated. 

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Table 4. Pharmacokinetic Parameters 
PK Parameter 
Definition 
Cmax  
Maximum observed plasma concentration 
Tmax 
Time of maximum observed plasma concentration; if it occurs at more than 
one time point, Tmax is defined as the first time point with this value 
AUC0-T 
Cumulative area under the plasma concentration time curve calculated from 0 
to TLQC using the linear trapezoidal method, where TLQC represents time of last 
observed quantifiable plasma concentration 
AUC0-∞  
Area under the plasma concentration time curve extrapolated to infinity, 
calculated as AUCT + CLQC/λZ, where CLQC is the measured concentration at 
time TLQC  
AUC0-T/∞ 
Relative percentage of AUC0-T with respect to AUC0-∞ 
λZ 
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
ClTOT/F 
Apparent Total Plasma Clearance, calculated as dose /AUC0-∞  
VD/F 
Apparent Volume of Distribution, calculated as dose / λZ*AUC0-∞  
Ae(0-t) 
Amount excreted in urine (Total lasmiditan concentration * Volume of Urine) 
fe 
Fraction of dose excreted in urine (Ae / dose) 
Clr 
Renal Clearance (Ae(0-t)/AUC0-T) 
 
Additional pharmacokinetic parameters may be calculated if deemed appropriate. 
Pharmacokinetic analyses will be generated using Phoenix® WinNonlin® Version 6.3 (or higher). 
7. ADVERSE EVENTS 
7.1. 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: 

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• 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). 
7.1.1. Severity Assessment 
All AEs will be graded as mild, moderate, or severe according to the following definitions: 
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. 

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7.1.2. 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 5. 
Table 5. 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). 
7.2. 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. 
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, 

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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. 
7.3. 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: 
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. 
PPD
PPD
PPD

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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. 
8. STATISTICAL ANALYSIS 
8.1. Analysis Sets 
8.1.1. Safety Analysis Set 
The safety population will include all subjects who received the investigational product under 
study. 
8.1.2. Pharmacokinetic Analysis Set 
All subjects who received lasmiditan, had no major protocol deviations, and completed the 
period with evaluable (sufficient and interpretable) data will be included in the PK analysis. 
Concentration data of the remaining subjects will be presented separately. 
If some subjects do not complete the sampling schedule resulting in an inadequately 
characterized AUC and elimination parameters, samples of these subjects could be included in 
the statistical pharmacokinetic analysis for only the Cmax and Tmax parameters. This decision is to 
be documented by the SRA department and approved by the sponsor before the start of the 
sample analysis by the bioanalytical facility. 

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8.2. Sample Size Determination 
There is no formal statistical sample size calculation for this study. A sample size of 32; 
including 8 subjects/patients for each renal function group (8 subjects with normal renal function 
8 patients with mildly impaired renal function, 8 patients with moderately impaired renal 
function, and 8 with severely impaired renal function) was chosen because it is considered 
typical for studies evaluating the effect of renal function on the pharmacokinetics of a drug. 
8.3. Statistical Analysis 
A detailed statistical analysis plan (SAP) describing the methodology to be used will be prepared 
prior to the completion of the clinical phase of the study. The sections below summarize the data 
analysis to be undertaken. 
8.3.1. Descriptive Analysis 
8.3.1.1. 
Safety Analyses 
Data to be listed by subject and summarized by group will include demographic data, AEs, vital 
signs, ECG parameters, and clinical laboratory evaluations. All values outside the clinical 
reference ranges will be flagged on the data listings. Other data to be listed by subject will 
include urinary drug screen, serology results, physical examination findings and concomitant 
medications. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA 
Version 19.0 or higher). Concomitant medications will be coded using the World Health 
Organisation drug dictionary (WHO-DDE March 1st, 2016). 
8.3.1.2. 
Pharmacokinetic Endpoint Analyses 
Descriptive statistics will be calculated for plasma concentrations at each individual time point 
and for all PK parameters. The individual plasma concentration/time profiles will be presented 
using the actual sampling times whereas the mean plasma concentration/time profiles will be 
presented using the theoretical sampling times. 
8.3.2. Statistical Methodology 
The natural logarithmic transformation of Cmax, AUC0-T, AUC0-∞, λZ, Ae(0-t), fe, Clr, ClTOT/F and 
VD/F as well as the rank-transformation of Tmax will be used for all statistical inference.  
Statistical analyses will be generated using validated SAS® (version 9.4 or higher) using the Reg 
(and Mixed, if applicable) procedure(s).  
The statistical analysis described in this section will be done using both eGFR and Cockcroft-
Gault estimate of the creatinine clearance. However, analysis using the eGFR will be considered 
as the primary analysis and the analysis using the Cockcroft-Gault estimate of the creatinine 
clearance will be considered as supportive. 

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Regression Analysis  
The eGFR and Cockcroft-Gault estimate of the creatinine clearance at baseline will be used as 
separate measures of renal function for a regression analysis to evaluate the relationships 
between estimated renal function and the PK parameters. For each PK parameter, a regression 
analysis will be performed to assess the impact of impaired eGFR and creatinine clearance 
(CLCR), using a regression model of the form α + β*eGFR (or CLCR) + ε where the errors (ε) 
will be assumed to be independent and normally distributed with mean zero and variance σ2. The 
parameter β represents the correlation between the relevant PK parameter and eGFR (or CLCR) 
which will be treated as a continuous variable. 
The hypothesis of the slope of trend being different from zero will be assumed if the two-sided 
test of the nullity of the parameter β is statistically significant at the 5% level.  
Analysis of Variance  
Based on the regression analysis described in the previous section, if the slope of trend of the 
regression analysis between a PK parameter and the estimated renal function (eGFR or CLCR) is 
found to be significant (p < 0.05), and if more than one group of subjects with impaired renal 
function are enrolled, an analysis of variance (ANOVA) will be performed to assess the 
difference in the PK parameter among the renal function groups. 
The renal function (normal, mild, moderate and severe) will be entered as a fixed effect in the 
ANOVA model. Pairwise comparisons of renal function groups will be generated using the 
Tukey-Kramer’s procedure of adjustment for multiple comparisons (if more than 2 renal function 
groups) and statistical significance will be assessed at the two-sided 5% level. The ratio of 
geometric LS means (of each renal function group being compared), with a corresponding 90% 
confidence interval (adjusted using Tukey-Kramer’s procedure if applicable), will be computed. 
Heterogeneity of variance among groups will be assumed.  
8.3.2.1. 
Interim Analysis 
First, subjects with severe renal impairment and healthy subjects with normal renal function will 
be enrolled. Samples will be assayed and PK will be performed. If substantial changes in the 
exposure of lasmiditan are observed in subjects with severe renal impairment compared to 
subjects with normal renal function, subjects with mild and moderate renal impairment will be 
enrolled. 
Interim analysis of subjects with severe renal impairment and healthy subjects with normal renal 
function will be performed as described in Section 8.3.2. 
9. ETHICS 
9.1. Institutional Review Board (IRB) 
This protocol and the ICF will be submitted to IRBs (or IECs) (one for each study center) prior 
to initiation of the study and the study will not start until the Board has approved the documents. 
Notification of the Board’s approval will be appended to the final report. 

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9.2. Ethical Conduct of the Study 
This study will be conducted in compliance with the study protocol, the ethical principles in the 
latest version of the Declaration of Helsinki, the ICH Guideline E6 for GCP, the FDA GCP Code 
of Federal Regulations (CFR) Title 21, part 56, European regulation EU 536/2014 and the 
Tri-Council Policy Statement (Canada). 
9.3. Participant Information and Consent 
Before inclusion in the study, each prospective subject will be given a full explanation of the 
purpose of the study, the procedures to be carried out and the potential hazards. Once this 
essential information is provided to the volunteer and once the physician in charge or designee 
has the conviction that the volunteer understands the implications of participating in the study, 
the volunteers will be required to read, sign and date a properly executed written informed 
consent form prior to enrollment. Subjects will be assured that they may withdraw from the study 
at any time without jeopardizing their medical care. They will be given a copy of their informed 
consent form. 
If an amended or revised ICF is introduced during the study, each subject’s further consent 
should be obtained. 
9.4. Subject Confidentiality 
The Investigators and the sponsor will preserve the confidentiality of all subjects taking part in 
the study, in accordance with GCP and local regulations. Subjects should be identified by a 
unique subject identifier on all study documents provided to the sponsor. In compliance with 
Federal regulations/ICH GCP Guidelines, it is required that the Investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and IRB access to 
review the subject’s original medical records for verification of study-related procedures and 
data. The investigator is obligated to inform the subject that his/her study-related records will be 
reviewed by the above named representatives without violating the confidentiality of the subject. 
10. DATA COLLECTION, RETENTION, AND MONITORING 
10.1. Case Report Forms 
A CRF is a gathering of all pertinent data collected for each subject included (i.e., who received 
an Investigational Product treatment) in a clinical trial. Once all CRF forms (including 
multi-subject CRF forms) are completed and reviewed. At Algorithme Pharma, the complete 
CRF will be approved and signed by the Study Manager, who received a signature delegation 
from the Principal Investigator. At the CIUSSS de l'est-de-l'île-de-Montréal - installation Hôpital 
Maisonneuve-Rosemont, the complete CRF will be approved and signed by the Principal 
Investigator. 
The original source documents and a copy of the corresponding CRFs will be retained by the 
Investigator. Copies of the CRFs will be provided to the sponsor. 

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10.2. Data Management and Processing 
Data entry will be performed according to clinical site facility procedures. Information will be 
entered into a Medrio database, which will be used for developing tables and listings for the final 
study report. Appropriately trained and designated individuals will be given access to the 
database and will perform entry of the data from the CRFs. The data management process will 
comply with all regulatory standards and will use from the clinical sites for generating the final 
locked database. 
10.3. Quality Assurance 
Designated personnel from Algorithme Pharma will be responsible for maintaining quality 
assurance (QA) and quality control (QC) systems to ensure that the portion of the trial conducted 
in the Algorithme Pharma clinic and the clinical/PK/statistical data are generated, documented 
and reported in compliance with the protocol and ICH Guideline E6 for Good Clinical Practices. 
Furthermore, Algorithme Pharma will qualify the vendor(s) or external clinical site(s) used in the 
conduct of the study. 
All parts of the bioanalytical phase of the study and all its documentation will be subject to 
inspection by the quality assurance unit of the bioanalytical facility to ensure that the data are 
generated, documented and reported in compliance with the protocol and applicable 
requirements as outlined in the FDA and OECD Principles of GLP. 
10.4. Record Retention 
All essential documents and records will be maintained by the study centers for a period of 
25 years. These documents may be retained for a longer period if required by the applicable 
regulatory requirement(s) (FDA CFR 312.57 (C)) or if needed by the sponsor. 
10.5. Monitoring of the Study 
The sponsor or its representative may visit the study facilities at any time in order to maintain 
current and personal knowledge of the study through review of the records, comparison with 
source documents, observation and discussion of the conduct and progress of the study. 
Algorithme Pharma will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s) by providing direct access to source data/documents. 
11. ADMINISTRATIVE PROCEDURES 
11.1. Adherence to Protocol 
Excluding an emergency situation in which proper treatment is required for the protection, safety 
and well-being of the study subjects, the study will be conducted as described in the approved 
protocol and performed according to ICH/GCP and FDA guidelines. Any deviation from the 
protocol will be recorded and explained. 
If amendments to the protocol and/or amendments or revisions to the ICF are required, the 
modifications will be documented and submitted to an IRB for approval. 

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11.2. Investigator Responsibilities 
The form “Qualified Investigator Undertaking” will be signed by the Investigator responsible for 
the medical decisions and care provided to the subjects (being also referred to as the “Qualified 
Investigator”) at each site prior to the commencement of his responsibilities with respect to the 
clinical trial, as required by the Food and Drug Regulations. The undertaking form will be 
maintained with the trial records and will be made available upon request. 
In addition, the FDA 1572 form, Statement of Investigator [Title 21, CFR Part 312], duly signed 
by the Principal Investigator and/or the Principal Investigator (if in charge of clinical assessment) 
as a condition for conducting the clinical investigation will be kept on file and will be available 
upon request. 
11.3. Delegation of Investigator Duties 
The Principal Investigator will ensure that all personnel involved in the trial are adequately 
qualified and informed about the protocol, any amendments to the protocol, the study treatments, 
and their trial-related duties and functions. 
The Principal Investigator will maintain a list of sub-investigator and other appropriately-
qualified persons to whom he delegates significant trial-related duties. 
Should the Principal Investigator delegate the supervision of the investigational product 
administration to a designated person, this individual must have the appropriate medical 
qualifications to effectively conduct or supervise any potential resuscitation procedures. 
11.4. Premature Termination or Suspension of a Study 
The sponsor or its representative may terminate the study at any time for scientific or corporate 
reasons. 
If the trial is prematurely terminated or suspended for any reason, Algorithme Pharma or the 
Principal Investigator should promptly inform the trial subjects, should assure appropriate 
therapy and follow-up for the subjects and should inform the regulatory authority (ies) when 
required. All procedures should be done according to clinical site procedures. 
11.5. Clinical Trial Application (CTA) 
A CTA must be submitted to Health Canada prior to the study, and a “No Objection Letter” 
(NOL) must be obtained before any drug administration. 
11.6. Exemption Application for Controlled Substances 
This trial does not involve a controlled substance. 
11.7. Publications 
The preparation and submission for publication of a manuscript containing the study results shall 
be in accordance with a process determined by mutual written agreement among the study 

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sponsor and participating institutions. The publication or presentation of any study results shall 
comply with all applicable privacy laws. 

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12. REFERENCES 
Investigational Brochure, Lasmiditan (COL-144), version 8.0, February 23, 2016 

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APPENDIX 01 
AMENDMENT 01 
 
 
RATIONALE: 
 
Reason for amendment: 
To update the blood volume required per PK sample and in 
the study. 
 
Requested by:  
 
CoLucid Pharmaceuticals, Inc. 
 
TEXT OF AMENDMENT: 
 
Amendment 01: 
 
1) Protocol, p. 32, Section 6.1.7 Pharmacokinetic Sampling, Changed: 
'Blood samples will be collected in one tube of 5 mL each.' 
To 
'Blood samples will be collected in one tube of 6 mL each.' 
2) Protocol, p. 32, Section 6.1.7 Pharmacokinetic Sampling, Changed: 
'The total volume of blood withdrawn, including ~21 mL required for screening, on-
study and poststudy tests, should not exceed 111 mL per subject.' 
To 
'The total volume of blood withdrawn, including ~21 mL required for screening, on-
study and poststudy tests, should not exceed 129 mL per subject.' 

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3) ICF, p. 5, Section Blood Sampling, Changed: 
'The first sample (1 x 5 mL, approximately 1 teaspoon) will be collected prior to the 
administration of the drug. All other samples (1 x 5 mL each, approximately 1 
teaspoon each) will be collected following drug administration.' 
To 
'The first sample (1 x 6 mL, approximately 1 teaspoon) will be collected prior to the 
administration of the drug. All other samples (1 x 6 mL each, approximately 1 
teaspoon each) will be collected following drug administration.' 
4) ICF, p. 5, Section Blood Sampling, Changed: 
'The total volume of blood drawn over an approximate 35-day period (including the 
screening period), including the volume necessary for the laboratory tests, should not 
exceed 111 mL (about ½ cup) per participant.' 
To 
'The total volume of blood drawn over an approximate 35-day period (including the 
screening period), including the volume necessary for the laboratory tests, should not 
exceed 129 mL (about ½ cup) per participant.' 
5) FCE, p. 5, Section Prélèvements sanguins, Changed: 
'Le premier échantillon (1 x 5 mL, environ 1 cuillère à thé) sera prélevé avant 
l'administration du médicament. Tous les autres échantillons (1 x 5 mL chacun, 
environ 1 cuillère à thé chacun) seront prélevés suivant la prise du médicament.' 
To 
'Le premier échantillon (1 x 6 mL, environ 1 cuillère à thé) sera prélevé avant 
l'administration du médicament. Tous les autres échantillons (1 x 6 mL chacun, 
environ 1 cuillère à thé chacun) seront prélevés suivant la prise du médicament.' 
6) FCE, p. 6, Section Prélèvements sanguins, Changed: 
'Le volume total de sang prélevé sur une période d’environ 35 jours (incluant la 
période de sélection), y compris celui nécessaire pour les tests de laboratoire, ne 
devrait pas excéder 111 mL (environ ½ tasse) par participant.' 
To 

PPD
PPD