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

Protocol H8H-CD-LAHF  
 
 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral 
Lasmiditan in Subjects with Normal and Impaired Hepatic Function 
 
NCT03040479 
 
Approval Date: 09-Jan-2016 
 
 
 

Clinical Study Report  
Project No COL MIG-114/H8H-CD-LAHF 
16.1 
STUDY INFORMATION 
16.1.1 
Protocol and Protocol Amendments 
Original Protocol CUD-P9-453 (COL MIG-114) 

 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study 
of Oral Lasmiditan in Subjects with Normal and Impaired Hepatic Function 
Protocol Number: 
CUD-P9-453 (COL MIG-114) 
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 
2017/01/09 
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. : 
 
Fax : 
 
-., Altasciences 
CLINICAL RESEARCH 
ALGORITHME 
PPD
PHARMA 
PPD
PPD
PPD
PPD
PPD
PPD

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
Version 1.0, 2017/01/09 
Page 2
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 ................................................................................................................................................ 15 
3.1. General Study Design .................................................................................................................................... 15 
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 ........................................................................................................................... 25 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
Version 1.0, 2017/01/09 
Page 3
6.
STUDY PROCEDURES AND GUIDELINES................................................................................................. 25 
6.1. Study Procedures ........................................................................................................................................... 30 
6.1.1. Physical Examination ............................................................................................................................. 30 
6.1.2. C-SSRS Questionnaire ........................................................................................................................... 30 
6.1.3. Vital Signs .............................................................................................................................................. 30 
6.1.4. Laboratory Evaluations .......................................................................................................................... 30 
6.1.4.1. Pregnancy Tests .............................................................................................................................. 31 
6.1.5. 12-Lead Electrocardiogram .................................................................................................................... 31 
6.1.6. Follow-up Call ....................................................................................................................................... 31 
6.1.7. Pharmacokinetic Sampling ..................................................................................................................... 31 
6.1.7.1. Sample processing, storage and shipping ........................................................................................ 32 
6.2. Bioanalytical Methods ................................................................................................................................... 32 
6.2.1. Aberrant values and retested samples .................................................................................................... 32 
6.2.2. Incurred sample reproducibility ............................................................................................................. 32 
6.3. Pharmacokinetic Measurements .................................................................................................................... 32 
7.
ADVERSE EVENTS .......................................................................................................................................... 33 
7.1. Definitions ..................................................................................................................................................... 33 
7.1.1. Severity Assessment ............................................................................................................................... 34 
7.1.2. Causality Assessment ............................................................................................................................. 35 
7.2. Routine Reporting ......................................................................................................................................... 35 
7.3. Serious Adverse Event Reporting ................................................................................................................. 36 
8.
STATISTICAL ANALYSIS .............................................................................................................................. 37 
8.1. Analysis Sets ................................................................................................................................................. 37 
8.1.1. Safety Analysis Set ................................................................................................................................ 37 
8.1.2. Pharmacokinetic Analysis Set ................................................................................................................ 37 
8.2. Sample Size Determination ........................................................................................................................... 38 
8.3. Statistical Analysis ........................................................................................................................................ 38 
8.3.1. Descriptive Analysis .............................................................................................................................. 38 
8.3.1.1. Safety Analyses ............................................................................................................................... 38 
8.3.1.2. Pharmacokinetic Endpoint Analyses ............................................................................................... 38 
8.3.2. Statistical Methodology ......................................................................................................................... 38 
8.3.2.1. Interim Analysis .............................................................................................................................. 39 
9.
ETHICS ............................................................................................................................................................... 39 
9.1. Institutional Review Board (IRB) ................................................................................................................. 39 
9.2. Ethical Conduct of the Study ......................................................................................................................... 39 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
Version 1.0, 2017/01/09 
Page 4
9.3. Participant Information and Consent ............................................................................................................. 39 
9.4. Subject Confidentiality .................................................................................................................................. 40 
10. DATA COLLECTION, RETENTION, AND MONITORING ...................................................................... 40 
10.1. Case Report Forms ........................................................................................................................................ 40 
10.2. Data Management and Processing ................................................................................................................. 40 
10.3. Quality Assurance ......................................................................................................................................... 40 
10.4. Record Retention ........................................................................................................................................... 41 
10.5. Monitoring of the Study ................................................................................................................................ 41 
11. ADMINISTRATIVE PROCEDURES .............................................................................................................. 41 
11.1. Adherence to Protocol ................................................................................................................................... 41 
11.2. Investigator Responsibilities ......................................................................................................................... 41 
11.3. Delegation of Investigator Duties .................................................................................................................. 41 
11.4. Premature Termination or Suspension of a Study ......................................................................................... 42 
11.5. Clinical Trial Application (CTA) .................................................................................................................. 42 
11.6. Exemption Application for Controlled Substances ....................................................................................... 42 
11.7. Publications ................................................................................................................................................... 42 
12. REFERENCES ................................................................................................................................................... 43 
13. Appendix A ......................................................................................................................................................... 44 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
Version 1.0, 2017/01/09 
Page 5
LIST OF IN-TEXT TABLES 
Table 1: Formulation of Lasmiditan, 200 mg Tablets .................................................................. 22
Table 2. Schedule of Assessments for All Subjects ...................................................................... 27
Table 3. Schedule of Pharmacokinetic Assessments .................................................................... 29
Table 4. Pharmacokinetic Parameters ........................................................................................... 33
Table 5. Adverse Event Relationship to Study Drug .................................................................... 35
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
Version 1.0, 2017/01/09 
Page 6
STUDY SYNOPSIS 
Name of Sponsor/Company: 
CoLucid Pharmaceuticals, Inc. 
Name of product: 
Lasmiditan 
Title of Study: 
A Phase I, Multicenter, Open-Label, Parallel-Group, 
Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects 
with Normal and Impaired Hepatic Function 
Study Development Phase: 
Phase I 
Objectives: 
The primary objective of this study is to evaluate the 
pharmacokinetic profile of lasmiditan following a single oral 
200 mg dose in subjects with mild and moderate hepatic function 
relative to matched, healthy control subjects with normal hepatic 
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, mild and moderate hepatic 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, 
single dose study. 
This study will enroll up to 24 subjects and will include 
2 hepatic-impaired subject groups and one group of control subjects 
with normal hepatic function. 
Approximately four subjects with mild hepatic impairment will be 
enrolled first (Group 1). To ensure subject safety, following dosing 
of these first four subjects, a safety meeting will take place to 
review the safety data prior to dosing additional subjects. After 
safety and PK results from the first four subjects have been 
reviewed, an additional four subjects with mild hepatic impairment 
(remainder of Group 1) will be enrolled concurrently with the 
moderated hepatic impairment group (Group 2). Thereafter, 
matched subjects with normal hepatic function (Group 3) will be 
enrolled. 
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 at least 10 hours prior to 
dosing until 36 hours after drug administration. 
Duration of Study: 
Up to 35 days including Screening. 
Study Population: 
Male and female adult subjects with normal hepatic function and 
male and female adult patients with mild or moderate hepatic 
impairment. Hepatic impairment will be classified using Child-
Pugh scores as follows: 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 7
5 to 6 points = Class A, mild hepatic impairment (Group 1); 
7 to 9 points = Class B, moderate hepatic impairment (Group 2); 
Normal hepatic function will be included in Group 3. 
Planned Number of Subjects: 
The study is planned to enroll up to 24 subjects: 8 subjects with 
mild hepatic impairment, 8 subjects with moderate hepatic 
impairment, and 8 healthy subjects with normal hepatic function. 
Subjects with moderate hepatic impairment will be enrolled as 
determined by review of safety data from the previously dosed 
group. 
Main Criteria for Inclusion: 
Male or female aged  ≥ 18 years 
Body mass index  ≥ 18.50 kg/m2 
Non clinical significant findings on 12-lead electrocardiogram 
(ECG) 
For females, negative result on a pregnancy test 
Group 1 (Mild Hepatic Impairment) 
Presence of mild hepatic impairment (Child-Pugh Class A) 
Group 2 (Moderate Hepatic Impairment) 
Presence of moderate hepatic impairment (Child-Pugh Class B) 
Group 3 (Normal Hepatic Function) 
Subjects will be matched by age (±10 years), weight (±20%), and 
gender to the pooled mean values of subjects with hepatic 
impairment. 
Hepatic function will be classified once at the Screening Visit, 
using the Child-Pugh score for each subject. 
Procedures and Assessments 
Safety evaluations including vital signs (body temperature, pulse 
rate and blood pressure), physical exams, safety laboratory tests 
(clinical chemistry, hematology, endocrinology, 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. 
Pharmacokinetic (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. 
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 adverse events/concomitant 
medication. 
Pharmacokinetics: 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 8
The following plasma PK parameters of lasmiditan will be 
calculated: Cmax, Tmax, AUC0-T, AUC0-∞, AUC0-T/∞, λz, Thalf, ClTOT/F 
and VD/F. 
Statistical Analyses: 
Safety data will be listed by subject and summarized by hepatic 
function group using frequency of event/abnormality or descriptive 
statistical summaries, as appropriate. 
PK parameters will be listed and summarized by hepatic function 
group using descriptive statistics. Mean and individual plasma 
concentration-time profiles will be presented graphically. 
A regression analysis in which the Child-Pugh classification and the 
pharmacokinetic parameters are treated as continuous variables will 
be used to evaluate the relationship between hepatic function and 
the estimated pharmacokinetic parameters of lasmiditan. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 9
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 
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 
LLOQ 
Lower limit of quantification 
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 
 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 10 
FACILITIES 
AUTHOR OF THE PROTOCOL: 
 
 
Algorithme Pharma 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
COORDINATING PRINCIPAL INVESTIGATOR: 
 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone: 
 
PRINCIPAL INVESTIGATOR: 
 
New Orleans Center for Clinical Research 
1928 Alcoa Highway, Suite 107  
Knoxville, TN 37920 
 
 
Orlando Clinical Research Center 
5055 South Orange Ave. 
Orlando, FL 32809 
 
MEDICAL LABORATORY*: 
Dynacare Solutions Santé 
4850 Dobrin St. 
Montreal, Quebec, Canada 
H4R 2P8 
Orlando Regional Medical Center Clinical Lab 
1414 Kuhl Ave  
Orlando FL 32809 
Laboratory Corporation of America (LapCorp) 
1924 Alcoa Highway 
Knoxville, TN 37920 
*Samples may be outsourced to affiliated accredited laboratory facilities, if necessary. 
..., Altasciences 
CLINICAL RESEARCH 
PPD
ALGORITHME PHARMA 
PPD
PPD
PPD
PPD
PPD

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 11 
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: 
 
Algorithme Pharma 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
STATISTICAL FACILITY: 
 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
DATA MANAGEMENT FACILITY: 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
..., Altasciences 
CLINICAL RESEARCH 
PPD
ALGORITHME PHARMA 
PPD
PPD
PPD

Research Protocol N° CUD-P9-453 
Sponsor Project N° COL MJG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
.., Altasciences 
~ CLINICAL RESEARCH 
'-,!. ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IMP 
AIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
Coordinating Principal Investigator 
Altascieoces Company Inc. ( 
doing business as Algorithme Pharma) 
 
Principal Investigator 
New Orleans Center for ClinfoaJ Research 
 
Principal Investigator 
Orlando Clinical Research Center 
Al'"" ciences Company Inc. (doing business as AJgorithme Pharma) 
Version 1.0, 2017/01/09 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Page 
PPD
12 
PPD
PPD
PPD
PPD

Research Protocol N° CUD-P9-453 
Sponsor Project N1 COL MIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
-, Altasciences 
~ CLINICAL RESEARCH 
u ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDITAN IN SUBJECTS 
WITH NORMAL AND IMPAIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
,
Coordinating Principal Investigator 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
 
Principal Investigator 
New Orleans Center for Clinical Research 
 
Principal Investigator 
Orlando Clinical Research Center 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
Version 1.0, 2017/01/09 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Page 
PPD
12 
PPD
PPD
PPD
PPD
PPD

Research Protocol N° CUD-P9-453 
Sponsor Project f
f
 
COL.MIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IIYIPAIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
New Orleans Center for Clinical Research 
 
 
Orlando Clinical Research Center 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
Version 1.0, 2017 /0 
l 
/09 
Date (yyyy/rnm/dd) 
Date (yyyy/mm/dd) 
Date (yyyy/mm/dd) 
Page 
PPD
12 
PPD
PPD
PPD
PPD
PPD

Research Protocol N° CUD-P9-453 
Sponsor Project N' COLMIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9--453 
Sponsor Project No COL-MIG-114 
-, A 
ltasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IMP 
AIRED HEPA TIC FUNCTION 
On behalf of the Sponsor, I am aware of, and agree to comply with, all of the procedures 
contained within this protocol: 
Digitally signed by Bernice Kuca 
ON: cn=Bernlce 
Kuca, o=CoLucld 
Pharmaceuticals, Inc, ou, 
email=bkuca@colucid.com, e=US 
Oate:2017.01.3117:51:15-05'00' 
 
Date (yyyy/mm/dd) 
 
CoLucid Pharmaceuticals, Inc. 
Version 1.0, 2017/01/09 
Page 
PPD
13 
PPD
PPD

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 14
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 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 15
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 and seems to have significant extrahepatic 
metabolism. This study was designed to evaluate the effects of impaired hepatic function on 
lasmiditan PK parameters, and on its safety. 
Results of this study may provide information on lasmiditan dosing recommendations in patients 
with hepatic 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 mild and moderate hepatic function relative 
to matched, healthy controls with normal hepatic 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, mild and moderate hepatic function. 
3. STUDY DESIGN 
3.1. General Study Design 
This is a multi-center, open-label, non-randomized, parallel-group, single dose study.  
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 16
This study will enroll up to 24 subjects and will include 2 hepatic impaired subject groups and 
one group of control subjects with normal hepatic 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. 
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To 
ensure subject safety, following dosing of these first four subjects, a safety meeting will take 
place to review the safety data prior to dosing additional subjects. After safety and PK results 
from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic 
impairment group (Group 2). Thereafter, matched subjects with normal hepatic function (Group 
3) will be enrolled. There will be up to 8 subjects in each of the following groups, based on 
hepatic function at screening: 
 Group 1: Mild hepatic impairment subjects (Child-Pugh Class A: 5 to 6 points) 
 Group 2: Moderate hepatic impairment subjects (Child-Pugh Class B: 7 to 9 points) 
 Group 3: Healthy subjects with normal hepatic function 
 
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 at least 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 24 subjects in 3 centers. Up to 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: 
 Experimental treatment: Lasmiditan 200 mg 
The total duration of the study is expected to be 35 days, including screening. 
The study may be stopped or interrupted at any time for safety, PK, or administrative reasons. 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 17
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: 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 18
- 
Participant is unable to procreate, defined as surgically sterile (i.e. has undergone a 
vasectomy within 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 
90 days after the drug administration 
7. Volunteer aged of at least 18 years 
8. Volunteer with a body mass index (BMI) ≥18.5 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 Hepatic 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, endocrinology, electrocardiogram [ECG], 
and urinalysis) 
13. Must match by gender, as well as to the pooled mean values for age (± 10 years) and 
weight (± 20%) of subjects with hepatic impairment 
Hepatic Impaired Subjects: 
14. Considered clinically stable in the opinion of the Investigator 
15. Presence of mild hepatic impairment (Child-Pugh Class A: 5-6 points) or moderate 
hepatic impairment (Child-Pugh Class B: 7-9 points) at screening (Appendix A) 
4.3. Exclusion Criteria 
All Subjects: 
1. Females who are pregnant or are lactating 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 19
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 tests (and HIV I & II screen at OCRC site) 
8. Females who are pregnant according to a positive pregnancy test 
9. Volunteers who took lasmiditan in the previous 28 days before Day 1 of this study 
10. Volunteers who took an Investigational Product (in another clinical trial) in the previous 
28 days before day 1 of this study 
11. Volunteers who have already participated in this clinical study 
12. 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 Hepatic Function: 
13. Seated pulse rate less than or equal 50 Beats per Minute (bpm) or more than 100 bpm at 
screening 
14. Seated blood pressure below 90/60 mmHg or higher than 140/90 mmHg at screening 
15. 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 
16. History of significant gastrointestinal, liver or kidney disease that may affect drug 
bioavailability 
17. Presence of significant cardiovascular, pulmonary, hematologic, neurological, 
psychiatric, endocrine, immunologic or dermatologic disease 
18. 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 
19. 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) 
20. Positive screening of alcohol and/or drugs of abuse 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 20
21. Positive results to Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C 
Virus (HCV (C)) tests 
22. Any clinically significant illness in the previous 28 days before day 1 of this study 
23. 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 
24. Volunteers who donated 50 mL or more of blood in the previous 28 days before day 1 of 
this study 
Hepatic Impaired Subjects: 
25. Seated pulse rate less than 40 bpm or more than 110 bpm at screening 
26. Seated blood pressure below 90/50 mmHg or higher than 170/100 mmHg at screening 
27. History of hepatic transplant 
28. Acute exacerbation of hepatic disease within 14 days of study drug administration 
29. History or presence, in the opinion of the Investigator, of significant clinically unstable 
respiratory, cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, 
immunologic, dermatologic, neurologic, or psychiatric disease  
30. Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c  10% 
31. Evidence of hepatocellular carcinoma present or acute hepatic disease from infection or 
drug toxicity at the time of screening 
32. Presence of severe encephalopathy 
33. Presence of surgically-created or transjugular intrahepatic portal systemic shunts 
34. History of any major surgery within 6 months before Day 1 
35. History of bariatric surgery or any other gastrointestinal surgery that may induce 
malabsorption 
36. Estimated creatinine clearance by Cockcroft-Gault equation  40 mL/min/1.73 m2 at 
screening 
37. Presence of clinically significant physical, laboratory, or electrocardiogram (ECG) 
finding that, in the opinion of the Investigator and/or Sponsor, may interfere with any 
aspect of study conduct or interpretation of results 
38. Subjects with acute, unstable, or untreated significant medical conditions. Subjects 
requiring treatment for hepatic impairment or other chronic disease (e.g., 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 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 21
during the study, and will be discussed on a case-by-case basis.  In all cases, the subjects’ 
treatment history must be reviewed and their enrollment must be agreed to by both the 
investigator and the Sponsor’s medical monitor 
39. Positive screening of alcohol and/or drugs of abuse unless results can be explained by a 
prescription medication 
40. Volunteers who donated 100 mL or more of blood in the previous 28 days before day 1 
of this study 
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 
 Adverse event (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 adverse event, 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. 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 22
5. STUDY TREATMENTS 
5.1. Description and Handling of Study Treatments 
5.1.1. Formulation of Test Product 
Lasmiditan is a 5-HT1F receptor agonists, developed by CoLucid Pharmaceuticals, Inc. for the 
acute treatment of migraine. Oral doses of lasmiditan 50 mg, 100 mg and 200 mg are being 
investigated in Phase 3 clinical trials. The Test product used in this study will be provided by the 
Sponsor as a single 200 mg oral tablet. 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 
drugs will meet applicable requirements of the protocol and the Canadian Health Products and 
the US Food and Drug Administration (FDA). 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 23
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-104°F). 
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 hepatic function, or into one of the 
two groups of subjects with varying degrees of hepatic impairment (mild or moderate hepatic 
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 
The 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.  
Subjects will be asked to fast overnight (no food or drink, except water) prior to 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 during the 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. 
The tablet must be swallowed whole and must not be chewed or broken. 
Study medications will be administered to each subject consecutively, and at adequate intervals, 
for the purpose of accurate sampling time. The date and time of each dose must be recorded. 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 24
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 
Hepatic-impaired subjects will be permitted to continue taking any prescription or OTC 
medication necessary for the management of their hepatic disease or other concurrent illness. 
The dosing schedules for such medications must be stable for 2 weeks before day 1 of the study 
(except for insulin) 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 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 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 dosing and during the study. 
If a medication (including OTC) other than those specified in the protocol is used after dosing 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. 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 25
5.6. Study-Specific Restrictions 
 Subjects will be requested to abstain from alcohol for 48 hours prior to dosing and during 
the 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. 
 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 adverse events 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 part is indicated with an "X" when the 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 26
assessments have to be performed. Any deviation from protocol should be noted in the Case 
Report Forms (CRFs) and the Sponsor should be notified. 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 27
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 & 
MedicalHistory 
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 Signsb 
X 
 
X 
 
X 
 
Height, Weight, and BMI 
X 
 
 
 
 
 
12-lead ECGc 
X 
 
X 
 
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 Evaluationsd 
X 
X 
 
 
X 
 
PK Blood Samplee 
 
 
X 
X 
 
 
Follow-up Call 
 
 
 
 
 
X 
Adverse Events Recording 
X 
X 
X 
X 
X 
X 
..., Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 28
a  Early Termination (ET).  
b Vital signs will be measured prior to dosing and approximately 2 and 4 hours after study drug administration, including orthostatic blood pressure. 
c  12-lead ECG will be performed prior to dosing and approximately 2 hours after study drug administration. 
d  Clinical laboratory tests (hematology, biochemistry, coagulation (screening only), endocrinology (screening only) and urinalysis) will be performed. On 
Day -1, these will be done in the evening prior to drug administration. 
e  PK blood samples will be collected according to schedule of PK assessments in Table 3. 
 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 29
Table 3. Schedule of Pharmacokinetic Assessments 
PK Blood Sampling 
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 
 
Time of PK sampling and dosing must be recorded. 
 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 30
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 adverse event (AE) monitoring. Body weight and height will be measured at 
Screening and BMI will be calculated. 
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 adverse events. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 31
 General biochemistry: Sodium, potassium, chloride, glucose, blood urea nitrogen (BUN), 
creatinine, ClCr, eGFR, total bilirubin, alkaline phosphatase, uric acid (screening only), 
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 
 Coagulation: PT/INR and PTT levels (screening only) 
 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 
 Endocrinology: Ferritin (screening only) 
 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 the study days where 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 recording. 
6.1.6. Follow-up Call 
A symptom-directed follow-up telephone call will be made to all subjects following drug 
application 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. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 32
The total volume of blood withdrawn, including ~47 mL required for screening and poststudy 
tests, should not exceed 155 mL per subject.  
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. 
6.2. Bioanalytical Methods 
Plasma lasmiditan concentrations will be measured according to a validated bioanalytical 
method.  
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. 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 are 
observed, the AUC parameters will not be estimated. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 33
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-∞ 
 
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 adverse event for which there is a reasonable possibility that 
the drug caused the adverse event. ‘Reasonable possibility’ means there is evidence to suggest a 
causal relationship between the drug and the adverse event. A suspected adverse reaction implies 
a lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
An AE may be: 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 34
 A new illness, 
 Worsening of a concomitant illness, 
 An effect of the study medication; 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 adverse events 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. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 35
7.1.2. Causality Assessment 
The Principal Investigator or a medical qualified designate will determine the relationship of any 
adverse event 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 
adverse event 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 adverse events extends from the 
screening visit until the follow-up call. During this period, all adverse events 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, 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 36 
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 (e.g., 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 representative: 
Bernice Kuca, Head Clinical/Regulatory Operations 
CoLucid Pharmaceuticals, Inc. 
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. 
-, Altasciences 
CLINICAL RESEARCH 
PPD
ALGORITHME PHARMA 
PPD
PPD

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 37
Algorithme Pharma will determine whether any serious unexpected related adverse event 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 
FDA and to the Health Canada Therapeutic Products Directorate (TPD). If so, Algorithme 
Pharma Inc, on the behalf of the Sponsor will report the event to the FDA, TPD, 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 has to 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. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 38
8.2. Sample Size Determination 
There is no formal statistical sample size calculation for this study. A sample size of 24; 
including 8 subjects/patients for each hepatic function group (8 subjects with normal hepatic 
function, 8 patients with mildly impaired hepatic function and 8 patients with moderately 
impaired hepatic function) was chosen because it is considered typical for studies evaluating the 
effect of hepatic 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. 
Adverse events 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, 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). 
Regression Analysis  
The Child-Pugh classification at baseline will be used the primary measure of hepatic function 
for a regression analysis to evaluate the relationships between estimated hepatic function and PK 
parameters. Hepatic function in affected subjects will be entered in separate regression models as 
the following: 
 Individual Child-Pugh scores; 
 Hepatic Impairment Group:  
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 39
o 1: Child-Pugh classification A;  
o 2: Child-Pugh classification B;  
o 3: Subject with normal hepatic function 
For each PK parameter, a regression analysis will be performed to assess the impact of impaired 
Hepatic Function, using a regression model of the form α + β*(Hepatic Function) + 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 
the Hepatic Function 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. 
8.3.2.1. 
Interim Analysis 
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To 
ensure subject safety, following dosing of these first four subjects, a safety meeting will take 
place to review the safety data prior to dosing additional subjects. After safety and PK results 
from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic 
impairment group (Group 2). Thereafter, matched subjects with normal hepatic function 
(Group 3) will be enrolled. 
Interim PK analysis of subjects with mild hepatic function will be performed as described in 
Section 6.3. 
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. 
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 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 40
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 clinical sites, 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. 
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 trial is conducted and 
clinical/PK/statistical data are generated, documented and reported in compliance with the 
protocol and ICH Guideline E6 for Good Clinical Practices. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 41
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. 
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. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 42
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 
Sponsor and participating institutions.  The publication or presentation of any study results shall 
comply with all applicable privacy laws. 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 43
12. REFERENCES 
Investigational Brochure, Lasmiditan (COL-144), version 8.0, February 23, 2016 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 

Research Protocol No CUD-P9-453 
Sponsor Project No COL MIG-114 
 
Version 1.0, 2017/01/09 
Page 44
13. APPENDIX A 
Child-Pugh Scores 
The score employs five clinical measures of liver disease. Each measure is scored 1-3, with 3 
indicating most severe derangement. 
 
1 Point 
2 Points 
3 Points 
Bilirubin, total, μmol (mg/dL) 
<34 (<2)  
34-50 (2-3) 
>50 (>3) 
Albumin, mg/L 
>35 
28-35 
<28 
INR 
<1.7 
1.71-2.20 
>2.20 
Ascites 
None 
Suppressed with medication 
Refractory 
Hepatic encephalopathy 
None 
Grade I-II  
(or suppressed with medication) 
Grade III-IV  
(or refractory) 
Class A=5-6 points; class B=7-9 points 
INR=International Normalized Ratio 
Source: http://www.doctorslounge.com/gastroenterology/scores/child.htm 
-, Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA