A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 (Galcanezumab) in Japanese Patients With Migraine
Phase: PHASE3
Conditions: Migraine
Sponsor: Eli Lilly and Company

Protocol I5Q-JE-CGAP 
 
 
A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 (Galcanezumab) in Japanese 
Patients with Migraine 
 
NCT02959190 
 
Approval Date: 2-Sep-2016 
 
 
 

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LY2951742 (galcanezumab)
Protocol I5Q-JE-CGAP
A Phase 3, Long-Term, Open-Label Safety Study of 
LY2951742(Galcanezumab)in Japanese Patients with 
Migraine
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company,or its subsidiaries,and 
should not be copied by or distributed to persons not involved in the clinicalinvestigation of
galcanezumab, unless such persons are bound by a confidentiality agreement with Eli Lilly 
and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
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Company requests consultation regarding release/redaction prior to any public release. In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
LY2951742(galcanezumab)
Study I5Q-JE-CGAPis along-term (12 month)Phase 3, multisite, randomized, open-label
study of galcanezumabin Japanese patients with migraine. Episodic migrainepatients will 
be rolled over from Study I5Q-JE-CGAN.Chronic migrainepatients will be enrolled 
separatelyfrom the extension ofStudy I5Q-JE-CGAN.
Approval Date: 02-Sep-2016 GMT
Eli Lilly Japan K.K. 
Kobe, Hyogo, Japan
Protocol Electronically Signed and Approved by Lilly on date provided below.

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Table of Contents
Section
Page
1.
Synopsis .............................................................................................................................8
2.
Schedule of Activities .......................................................................................................11
3.
Introduction ......................................................................................................................14
3.1.
Study Rationale............................................................................................................14
3.2.
Background..................................................................................................................14
3.3.
Benefit/Risk Assessment..............................................................................................15
4.
Objectives and Endpoints..................................................................................................16
5.
Study Design.....................................................................................................................19
5.1.
Overall Design .............................................................................................................19
5.2.
Number of Participants.................................................................................................20
5.3.
End of Study Definition ...............................................................................................20
5.4.
Scientific Rationale for Study Design...........................................................................20
5.5.
Justification for Dose ...................................................................................................21
6.
Study Population...............................................................................................................22
6.1.
Inclusion Criteria..........................................................................................................22
6.2.
Exclusion Criteria ........................................................................................................23
6.3.
Lifestyle Restrictions....................................................................................................25
6.4.
Screen Failures.............................................................................................................25
7.
Treatments........................................................................................................................26
7.1.
Treatments Administered .............................................................................................26
7.1.1.
Packaging and Labeling .......................................................................................26
7.1.2.
Medical Devices...................................................................................................27
7.2.
Method of Treatment Assignment ................................................................................27
7.2.1.
Selection and Timing of Doses.............................................................................27
7.3.
Blinding .......................................................................................................................27
7.4.
Dosage Modification....................................................................................................27
7.5.
Preparation/Handling/Storage/Accountability...............................................................28
7.6.
Treatment Compliance .................................................................................................28
7.7.
Concomitant Therapy...................................................................................................28
7.8.
Treatment after the End of the Study............................................................................28
7.8.1.
Continued Access.................................................................................................28
8.
Discontinuation Criteria ....................................................................................................29
8.1.
Discontinuation from Study Treatment.........................................................................29
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................29

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8.1.2.
Discontinuation of Inadvertently Enrolled Patients...............................................29
8.2. Discontinuation from the Study....................................................................................29
8.3. Lost to Follow-Up........................................................................................................30
8.4
Discontinuation of Study Sites.....................................................................................30
8.5
Discontinuation of the Study........................................................................................30
9.
Study Assessments and Procedures...................................................................................31
9.1. Effectiveness Assessments...........................................................................................31
9.1.1.
Primary Effectiveness Assessments......................................................................31
9.1.2.
Secondary Effectiveness Assessments..................................................................31
9.1.2.1.
Patient Global Impression of Severity.............................................................31
9.1.2.2.
Patient Global Impression of Improvement.....................................................31
9.1.3.
Appropriateness of Assessments..........................................................................31
9.2. Adverse Events............................................................................................................32
9.2.1. 
Serious Adverse Events........................................................................................32
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................33
9.2.1.2.
Adverse Event Monitoring with a Systematic 
Questionnaire.................................................................................................33
9.2.2.
Complaint Handling.............................................................................................34
9.3. Treatment of Overdose.................................................................................................34
9.4. Safety...........................................................................................................................34
9.4.1.
Vital Signs and Weight........................................................................................34
9.4.2.
Electrocardiograms..............................................................................................34
9.4.3.
Laboratory Tests..................................................................................................34
9.4.4.
Safety Monitoring................................................................................................35
9.5. Pharmacokinetics.........................................................................................................35
9.6. Pharmacodynamics......................................................................................................35
.......................................................................................................................36
..........................................36
9.8. Biomarkers...................................................................................................................36
9.8.1.
Samples for Immunogenicity Research.................................................................37
9.9. Medical Resource Utilization and Health Economics...................................................37
10. Statistical Considerations..................................................................................................39
10.1. Sample Size Determination..........................................................................................39
10.2. Populations for Analyses..............................................................................................39
10.3. Statistical Analyses......................................................................................................39
10.3.1. General Statistical Considerations........................................................................39
10.3.2. Treatment Group Comparability...........................................................................40
10.3.2.1. Patient Disposition..........................................................................................40
CCI

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10.3.2.2. Patient Characteristics....................................................................................40
10.3.2.3. Concomitant Therapy.....................................................................................40
10.3.2.4. Treatment Compliance....................................................................................40
10.3.3. Primary and Secondary Analyses.........................................................................41
10.3.3.1. Primary Analyses...........................................................................................41
10.3.3.2. Secondary Analyses........................................................................................41
10.3.3.2.1. Effectiveness Analyses.............................................................................41
10.3.4. Tertiary/Exploratory Analyses..............................................................................42
10.3.5. Other Safety Analyses..........................................................................................42
10.3.5.1. Immunogenicity Analyses..............................................................................42
42
10.3.7. Other Analyses.....................................................................................................43
10.3.7.1. Medical Resource Utilization and Health Economics......................................43
10.3.8. Interim Analyses..................................................................................................43
11. References........................................................................................................................44
12. Appendices.......................................................................................................................46

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List of Tables
Table
Page
Table CGAP.4.1.
Objectives and Endpoints .......................................................................16
Table CGAP.4.2.
Migraine and Headache Endpoint Definitions.........................................18
Table CGAP.7.1.
Treatment Regimen ................................................................................26

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List of Figures
Figure
Page
Figure CGAP.5.1.
Illustration of study design for Clinical Protocol I5Q-JE-
CGAP.....................................................................................................19

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................47
Appendix 2.
Clinical Laboratory Tests........................................................................50
Appendix 3.
Study Governance Considerations ..........................................................51
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent 
Abnormality ...........................................................................................55

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1.
Synopsis
Title of Study:
A Phase 3, Long-Term, Open-Label Safety Study of Galcanezumab in Japanese Patients with 
Migraine
Rationale:
Study I5Q-JE-CGAP (CGAP) is intended to assess the long term safety of galcanezumab
(120 mg/month or 240 mg/month) in Japanese patients with migraine.
Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To evaluate the long-term safety and tolerability of 
galcanezumab 120 mg/month or 240 mg/month in 
patients with migraine for 1 year of treatment
Analysis of:

treatment-emergent adverse events (TEAEs)

discontinuation rates

vital signs and weight

electrocardiograms (ECGs)

laboratory measures

other safety parameters, including suicidality 
using the C-SSRS
Secondary

To characterize the long-term 
pharmacokinetics, pharmacodynamics and 
immunogenicity of galcanezumab

Assessment of serum concentrations of
galcanezumab to enable a pharmacokinetic
evaluation

Assessment of plasma concentrations of
CGRP to enable a pharmacodynamic 
evaluation of target engagement of 
galcanezumab

Assessment of the development and 
consequences of ADA to galcanezumab

To evaluate the long-term effectiveness of 
galcanezumab in the prevention of migraine

Mean change from baseline (Visit 3) in the 
number of migraine headache days

Mean change from baseline in the number of 
headache days

Proportion of patients meeting 50% response
criteria (reduction of at least 50% in the
number of migraine headache days)

Mean change from baseline in the frequency
of medication use for the acute treatment of
migraines or headaches

Mean change from baseline in PGI of illness 
as measured by PGI-Severity

PGI of improvement as measured by

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Objectives
Endpoints
PGI-Improvement

Mean change from baseline in the number of 
monthly migraine headache days or headache 
days requiring medication for the acute 
treatment of migraine headache or headache

Mean change from baseline in the number of 
monthly migraine headache days requiring 
medication for the acute treatment of migraine 
headache

To evaluate the long-term effect of 
galcanezumab on quality of life

Mean change from baseline to endpoint in the
evaluation of the MIDAS total score and
individual items

Mean change from baseline to endpoint in the
MSQ (v2.1) total score and individual 
domains

Change from baseline in HCRU and 
employment status

To evaluate patient satisfaction with 
medication 

Satisfaction with medication using the 
PSMQ-M

To evaluate safety and residual treatment 
effect during the post-treatment follow-up 
period

Analysis of safety parameters

Time to first loss of response (when patient no
longer meets 50% response criteria and/or
starts treatment using migraine prevention
medication) during the post-treatment follow-
up phase
Abbreviations:  ADA = anti-drug antibodies; CGRP = calcitonin gene-related peptide; C-SSRS = Columbia Suicide Severity Rating Scale;
HCRU = health care resource utilization; ECGs = electrocardiograms; MIDAS = Migraine Disability Assessment test; 
MSQ (v2.1) = Migraine Specific Quality of Life Questionnaire version 2.1; PGI = Patient Global Impression Questionnaire; 
PSMQ-M = Patient Satisfaction with Medication Questionnaire-Modified; TEAE = treatment-emergent adverse event.
Summary of Study Design:
Study CGAP is a multisite, randomized, open-label trial of Japanese patients with episodic 
migraine (EM), with the addendum for patients with chronic migraine (CM). The definitions of 
EM and CM are dependent on the frequency of migraine headache with referring International 
Classification of Headache Disorders- (ICHD-) 3beta criteria [see details in Section 6 of this 
protocol and in the CGAP protocol addendum (1), respectively]. A major part of this study is an 
open-label extension study for patients with EM who complete the treatment period in Study 
I5Q-JE-CGAN (CGAN) and are willing to continue the study.
Patients with CM
The descriptions relevant for patients with CM are involved in both this protocol and the CGAP 
protocol addendum (1).  
To align the study schedule for patients with both EM and CM, the beginning of Study CGAP
for patients with EM is set as Visit 3, not Visit 1; Visit 3 is the first injection visit for patient with 

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both EM and CM in Study CGAP.  Sites for patients with CM and sites for patients with EM are 
separated. 
Treatment Arms and Duration:
There will be 2 treatment arms:  galcanezumab 120 mg/month; and galcanezumab
240 mg/month. The detail is shown in Table CGAP.7.1.  The patients will be randomized in a 
1:1 ratio to receive 120 mg/month of galcanezumab, or 240 mg/month of galcanezumab at 
Visit 3 of Study CGAN for the patients who roll over from Study CGAN (see Section 7.2).  
Patients who were in the galcanezumab treatment arms for Study CGAN continue with the same 
dose in Study CGAP, while patients who were in the placebo arm in Study CGAN are 
randomized to 120 mg or 240 mg at Visit 3 of Study CGAN (randomization ratio = 1:1).
If patients who roll over from Study CGAN are confirmed eligible, the patients will begin a 
12-month treatment period (Study Period III).  This will be followed by a 4-month follow-up 
period during which patients will no longer receive any study drug (Study Period IV).
Number of Patients:
Approximately 300 patients (approximately 150 patients per arm) will be enrolled for the 
purposes of regulatory registration, to ensure at least 100 patients per arm with 1 year of 
exposure.  It is assumed that 30% of patients will not complete the 12-month treatment period
(Study Period III).
Approximately 240 EM patients will be rolled-over from Study CGAN (120 patients for the
Study CGAP 120 mg arm, 120 patients for the Study CGAP 240 mg arm).  Approximately 
60 CM patients will be enrolled (30 patients for Study CGAP 120 mg arm, 30 patients for Study 
CGAP 240 mg arm).
Statistical Analysis:
Effectiveness and safety analyses will be conducted using an intent-to-treat (ITT) population, 
which is to include all patients who receive at least 1 dose of investigational product. 
Statistical summary will be presented by each treatment arm.
In the summary of categorical variables (binary variables), the frequency and percentage will be 
presented. 
In the summary of continuous variables, the mean, standard deviation, minimum, median, and 
maximum will be reported. 
An interim analysis will be conducted in support of regulatory submissions.

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2. Schedule of Activities
This is for the EM patients who roll over from Study CGAN. 
Study Period (SP)
SP III – Treatment
SP IV –
Follow-up
(Target) Interval (days) 
since previous visit
0
14
16
30
30
30
30
30
30
30
30
30
30
30
60
60
Interval allowance (days) 
compared from previous 
visit
±3
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Visit
3a
4
5
6
7
8
9
10
11
12
13
14
15
16/ ET
17
18/ ET
Month
0
(D 14)
1
2
3
4
5
6
7
8
9
10
11
12
14
16
Assessments and Procedures
Informed consent
X
Inclusion/exclusion
X
Demographics
X
Physical examinationb
X
Height
k
Weight
X
X
X
X
Waist and hip 
circumference
k
Medical History
k
Pre-specified migraine 
history
k
Substance use
k
Prior Therapy (Migraine 
Medication)
k
ECGc
X
X
X
X
Vital signs
d
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment of migraine 
and headache dayse
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Paper-diary training
X
Clinical Laboratory Tests and Sampling Schedules
Hematology
X
X
X
X
X
X
Clinical chemistry
X
X
X
X
X
X
HbA1c
X
X
X
X
Urinalysisf
X
X
X
X

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Study Period (SP)
SP III–Treatment
SP IV–
Follow-up
(Target) Interval (days) 
since previous visit
0
14 
16 30 30 30 30 30 30 30 30 30 30 
30 
60 
60
Interval allowance (days) 
compared from previous 
visit
±3 
±3 ±7 ±7 ±7 ±7 ±7 ±7 ±7 ±7 ±7 ±7 
±7 
±7 
±7
Visit
3a
4 
5 
6 7 8 
9
10 11
12 13 14 15 16/ ET
17 18/ ET
Month
0
(D 14) 1 
2 3 4 
5 
6 
7 
8 
9
10 11 
12 
14 
16
Serum Pregnancy (for 
women of childbearing 
potential)gor FSHat Visit 
3(for women who have 
evidence of cessation of 
menses for at least 12 
months)
X
X
X
Urine pregnancy
g
X 
X X X X X X X X X X X
Immunogenicity
h
X 
X 
X X X
X
X
X
X
Biomarker storage sampleh
X 
X 
X
X
X
X
X
 
X 
X 
X X X
X
X
X
X
PK blood sample
h
X 
X 
X X X
X
X
X
X
 
h
X
X
X
X
Study drug administered
i
X
X 
X X X 
X 
X 
X 
X X 
X 
X
Scales, Questionnaires, and Outcome Measures
MIDAS
X
X
X
X
X
X
MSQ (v2.1)
X
X 
X X
X X
X
X
X 
X 
X
HCRU and Employment 
Status
X
X 
X X X 
X 
X 
X 
X X 
X 
X 
X 
X 
X
PSMQ-M
X
X
X
X
PGI-S
X
X X X X X X
X
X
PGI-I
X 
X X
X X
X
X
X
X
C-SSRS/SHSF, SHFU
j
X
X 
X X X 
X 
X 
X 
X X 
X 
X 
X 
X 
X
CCI
Abbreviations:  CGRP = calcitoningene-related peptide; C-SSRS = Columbia Suicide Severity Rating Scale; D = Day; 
ECG=electrocardiogram;EM = episodic migraine; ET = early termination; FSH = follicle stimulating hormone; HbA1c= glycated 
hemoglobin; HCRU = Health Care Resource Utilization; MIDAS = Migraine Disability Assessment test; MSQ (v2.1) = Migraine Specific 
Quality of Life Questionnaireversion 2.1; PGI-I = Patient Global Impression of Improvement; PGI-S = Patient Global Impression of 
Severity;PK = pharmacokinetic(s); PSMQ-M = Participant Satisfaction with Medication Questionnaire-Modified; RNA=Ribonucleic acid; 
SP = Study Period.SHSF = Self-harm supplement form; SHFU = Self-harm follow-up form.
a Visit 3is the same as Visit 12 of Study CGAN.  Patients will receive injections of galcanezumabafter all other visit proceduresat Visit 12 of 
Study CGANare completedand confirmationof eligibility.The data of weight, ECG, Vital signs, Assessment of migraine and headache 
days, Hematology, Clinical chemistry, HbA1c, Urinalysis, Serum Pregnancy (for women of childbearing potential) or FSH (for women who 
have evidence of cessation of menses for at least 12 months), Urine pregnancy, Immunogenicity, Biomarker storage sample, CGRP plasma 
CCI

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sample, PK blood sample, Whole blood RNA/epigenetic sample, MIDAS, MSQ, HCRU and Employment Status, PGI-S, and C-
SSRS/SHSF, SHFUat Visit3of study CGAP will utilize the data at Visit 12 of Study CGAN.
b Physical examinations at screening must include a neurological exam.
c ECG as single, 12-lead digital will be performed at Visit 3, Visit 10, Visit 16,and Visit 18or early termination.  Note:  the Visit 3ECG 
should be collected prior to blood draws and dosing.  Patients must be supine for approximately 5 to 10 minutes before ECG collection and 
remain supine but awake during ECG collection.
d Vital signs taken at every office visit will include body temperature, blood pressure, and pulse.  Blood pressure and pulse will be measured in 
triplicate in the sitting position,and should be measured prior to blood draws.  Blood pressure will be assessed by utilizing a calibrated 
machine that will be provided to the sites (see Section 9.4.1for guidance on vital signs).
e Patients will use a paper-based headache diary (paper diary) provided by sponsor, which can take information of the frequency of headaches, 
migraine headaches, and medication for migraine or headache.  Investigators are responsible for data integrity of paper diary.
f In the event of a positive urine leukocyte esterase result, a repeat urine sample will be collected and shipped to the central laboratory.
g Urine pregnancy tests to be performed every month during SPIIIafter baseline and as indicated based on the investigator’s judgment. 
Apositive urine pregnancy test must be followed by a serum pregnancy test for confirmation.
h Immunogenicity, biomarker sample,
, PK sampling, and whole blood RNA/epigenetic sampleto be performed at the 
indicated visits and prior to dose administration if the visit is a dosing visit.  Samples will be taken in the event of early termination. 
Thetiming of samples will be recorded.  Immunogenicity and PK samples may also be collected in the event of a systemic 
allergic/hypersensitivity reaction (see Section 9.4.3). 
i Patients will receive injections ofgalcanezumabafter all other visit procedures are completed.  Following the dose at Visit 3, patients will be 
observed for at least30 minutes at the site.Following subsequent doses, patients will be observed for at least30 minutes post-injection if 
they have a significant adverse event following any previousinjection and/or they are judged by the investigator to have risk of a significant 
adverse event after injection.
j The C-SSRS and SHSF (and SHFU,when applicable) will be completed at scheduled and unscheduled office visits.
k The baselineassessmentof StudyCGAN will be used.
Note:  Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may be required in follow-up with patients in 
consultation with the Lilly, or its designee, clinical research physician.  See Appendix4
CCI
for more details regarding specific hepatic 
monitoring tests.  If the patient has discontinued the trial and returns for hepatic follow-up, the site should use the 800series as the visit 
designation.

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3.
Introduction
3.1.
Study Rationale
Study I5Q-JE-CGAP (CGAP) is a Phase 3 study conducted in Japan intended to assess the safety 
of galcanezumab (120 mg/month or 240 mg/month) in Japanese patients with migraine.
3.2.
Background
Migraine is a chronic, debilitating condition that impacts the quality of patients’ lives.  In Japan, 
the prevalence of migraine is estimated to range from 6.0% to 8.4% (Sakai and Igarashi 1997;
Takeshima et al. 2004), which is not different from that in the United States (US). More than 
25% of Japanese patients with migraine suffer more than 3 headache days per month, which lead 
to loss of working days. On the other hand, less than 10% of migraine patients have continuous 
visits to the hospital (Takeshima et al. 2004). These data suggest that Japanese migraineurs have 
a considerable amount of socioeconomic burden, and they are not satisfied with the value of 
medical services, compared to the loss of payment from missing working days.
Migraine has 2 major subtypes: migraine with aura; and migraine without aura. The recurrent 
episodes of headache is a characteristic of both subtypes; therefore, they are collectively called 
episodic migraine (EM). A subgroup of migraine patients can gradually worsen into a more 
severe condition with very frequent episodes of headache, and this condition is categorized as 
chronic migraine (CM). The International Criteria of Headache Disorders- (ICHD-) 3beta
defines CM as a headache occurring on 15 or more days per month for more than 3 months, and 
which has the features of a migraine headache on at least 8 days per month.  Although the 
prevalence of CM in Japan is still uncertain, it can be estimated to be approximately 7.0% of the 
total population with migraine (Takeshima 2004), which is consistent with the prevalence in the 
US (Buse 2012).
Calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of migraine.  
Infusion of CGRP to individuals with a history of migraine can trigger migraine attacks 
(Lassen et al. 2002). The efficacy of small-molecule CGRP antagonists was demonstrated in the 
acute treatment of migraine (Peroutka 2014) and in the prevention of migraine (Ho et al. 2014). 
Increased serum CGRP levels are reported in EM patients, as well as in those with CM 
(Cernuda-Morollón et al. 2013). This evidence suggests that the neutralization of the CGRP 
signal may represent a promising therapeutic approach for the prevention of EM and CM.
Galcanezumab is a humanized monoclonal antibody that potently and selectively binds to CGRP, 
preventing CGRP-mediated biological effects. In studies of patients with migraine (Studies I5Q-
MC-ART1 [ART-01] and I5Q-MC-CGAB [CGAB]), the efficacy data have demonstrated that 
galcanezumab had significantly greater mean reductions than placebo in the number of migraine 
headache days and other efficacy parameters. In these 2 studies, the most frequently reported 
adverse events (AEs) included: injection site pain, upper respiratory tract infection, abdominal 
pain, dizziness, injection site erythema, rash, hypertension, and nasopharyngitis.

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3.3.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated AEs of galcanezumab are to be found in the Investigator’s Brochure 
(IB).

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4.
Objectives and Endpoints
Table CGAP.4.1 shows the objectives and endpoints of the study.  Table CGAP.4.2 provides 
definitions for the terms referenced below.
Table CGAP.4.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the long-term safety and tolerability of 
galcanezumab 120 mg/month or 240 mg/month in 
patients with migraine for 1 year of treatment.
Analysis of:

treatment-emergent adverse events (TEAEs)

discontinuation rates

vital signs and weight

electrocardiograms (ECGs)

laboratory measures

other safety parameters, including suicidality 
using the Columbia Suicide Severity Rating 
Scale (C-SSRS)
Secondary

To characterize the long-term 
pharmacokinetics, pharmacodynamics and 
immunogenicity of galcanezumab

Assessment of serum concentrations of
galcanezumab to enable a pharmacokinetic 
evaluation

Assessment of plasma concentrations of CGRP 
to enable a pharmacodynamic evaluation of
target engagement of galcanezumab

Assessment of the development and 
consequences of ADA to galcanezumab in 
patients exposed to drug 

To evaluate the long-term effectiveness of 
galcanezumab in the prevention of migraine

Mean change from baseline (Visit 3) in the 
number of migraine headache days

Mean change from baseline in the number of 
headache days

Proportion of patients meeting 50% response
criteria (reduction of at least 50% in the number 
of migraine headache days)

Mean change from baseline in the frequency of 
medication use for the acute treatment of
migraines or headaches

Mean change from baseline in PGI of illness as 
measured by PGI-S

Patient’s global impression of improvement as
measured by PGI-I

Mean change from baseline in the number of 
monthly migraine headache days or headache 
days requiring medication for the acute 
treatment of migraine headache or headache

Mean change from baseline in the number of 
monthly migraine headache days requiring 
medication for the acute treatment of migraine 

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Objectives
Endpoints
headache

To evaluate the long-term effect of 
galcanezumab on quality of life

Mean change from baseline to endpoint in the
evaluation of the MIDAS total score and
individual items

Mean change from baseline to endpoint in the
MSQ (v2.1) total score and individual domains

Change from baseline in HCRU and 
employment status

To evaluate patient satisfaction with medication 

Satisfaction with medication using 
the PSMQ-M

To evaluate safety and residual treatment effect 
during the post-treatment follow-up period

Analysis of safety parameters

Time to first loss of response (when patient no
longer meets 50% response criteria and/or starts 
treatment using migraine prevention
medication) during the post-treatment follow-
up phase
Abbreviations:  ADA = anti-drug antibodies; CGRP = Calcitonin gene-related peptide; C-SSRS = Columbia Suicide Severity Rating Scale; 
ECGs = Electrocardiograms; HCRU = Health Care Resource Utilization; MIDAS = Migraine Disability Assessment test; 
MSQ (v2.1) = Migraine Specific Quality of Life Questionnaire version 2.1; PGI-I = Patient Global Impression of Improvement; 
PGI-S = Patient Global Impression of Severity; PSMQ-M = Patient Satisfaction with Medication Questionnaire-Modified; 
TEAEs = treatment-emergent adverse events.

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Table CGAP.4.2.
Migraine and Headache Endpoint Definitions
Diagnosis
Definition/Criteria
Migraine headache (patients with EM only)
A headache, with or without aura, of ≥30 minutes 
duration with both of the following required features (A 
and B):
A. At least 2 of the following headache characteristics:

Unilateral location

Pulsatile quality

Moderate or severe pain intensity

Aggravation by or causing avoidance of routine 
physical activity
AND
B. During headache at least one of the following:

Nausea and/or vomiting

Photophobia and phonophobia
(Definition adapted from the IHS ICHD-3 beta)
Probable migraine headache (patients with EM only)
A headache missing 1 of the migraine features in the 
IHS ICHD-3 beta definition such that 1 feature in 
criteria A is missing or 1 feature in criteria B is missing; 
ie, meet at least 2 A criteria and none of the B criteria, or 
meet 1 of the A criteria and at least 1 of the B criteria.
Migraine headache day 
A calendar day on which a migraine headache or 
probable migraine headache occurred.
Migraine headache attack
Beginning on any day a migraine headache and/or a 
probable migraine headache is recorded, and ends when 
a migraine-free day occurs. 
Non-migraine headache
All headaches of at least 30 minutes’ duration not 
fulfilling the definition of migraine or probable migraine 
are classified as non-migraine headaches.
Non-migraine headache day
A calendar day on which a non-migraine headache 
occurred.
Headache day
A calendar day on which any type of headache occurs, 
(including migraine headache, probable migraine 
headache, and non-migraine headache).
Migraine headache days with abortive (acute) 
medication use
Calendar days on which migraine or probable migraine 
occurs requiring abortive (acute) medication.
Migraine headache days or headache days with abortive 
(acute) medication use
Calendar days on which any types of headache occurs 
requiring abortive (acute) medication.
Abbreviations:  EM = episodic migraine; ICHD = International Classification of Headache Disorders; 
IHS = International Headache Society.

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5.
Study Design
5.1.
Overall Design
Study CGAP is a multisite, randomized, open-label, trial with 4 study periods.  A major part of 
this study is a roll over study from parental Study I5Q-JE-CGAN (CGAN) for EM patients who 
complete Study Period III in Study CGAN, and are willing to continue the study.  
In Study Periods III and IV, patients will use a paper-based headache diary (paper diary) 
provided by the sponsor, which can take information of the frequency of headaches, migraine 
headaches, and medication for migraine or headache.  Investigators are responsible for data 
integrity of the paper diary.
Note: the end-of-treatment phase of Study CGAN (Visit 12 of Study CGAN) is equal to the 
Visit 3 of Study CGAP. The beginning of Study CGAP for EM patients is Visit 3, not Visit 1;
Visit 3 is the first injection visit for both EM patients and CM patients in Study CGAP.
Figure CGAP.5.1 illustrates the study design.
Figure CGAP.5.1.
Illustration of study design for Clinical Protocol I5Q-JE-CGAP.
At Visit 3 of Study CGAP (Visit 12 of Study CGAN), the study and potential risks will be 
explained to patients.  At this time, the patient will sign and date the informed consent form 
(ICF).
Study Period III (SPIII): This is a 12-month treatment period.  If a patient meets all 
requirements for study eligibility, the patient will receive galcanezumab at 120 mg/month or 
240 mg/month. Patients that were in the 120-mg arm in Study CGAN will continue in the 

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120-mg arm in Study CGAP. Patients that were in the 240-mg arm in Study CGAN will 
continue in the 240-mg arm in study CGAP. And patients that were in the placebo arm in Study 
CGAN will be assigned to either the 120-mg or the 240-mg arm in Study CGAP. The dosing at 
Visit 3 is blinded for all patients (see Section 7.3).  
Patients will be trained to keep track of their migraine and headache days, as well as their 
medication use days using a paper-based headache diary (paper diary) by the site staff.  
Retraining will be conducted, as necessary, based upon review of paper diary data.
After study drug is administered at Visit 3, the patient must remain at the site for observation for 
at least 30 minutes post-injection. Following subsequent doses, patients will be observed for at 
least 30 minutes post-injection if they have a significant adverse event following any previous
injection and/or they are judged by the investigator to have risk of a significant adverse event 
after injection.
Safety assessments will include treatment-emergent adverse events (TEAEs), vital signs, weight, 
electrocardiograms (ECGs), and laboratory tests. 
If a patient discontinues early for any reason during SPIII, the patient will be expected to take the 
measurement for Early Termination (ET) and to enter the post-treatment follow-up period 
(SPIV) to assess safety.
Study Period IV (SPIV):  This is a 4-month follow-up period. Patients will no longer receive 
investigational product. However, patients will continue to track their headache information. 
Site visits are every 2 months.
Patients who discontinue for any reason during SPIV will be expected to take the measurement 
for ET.
5.2.
Number of Participants
Approximately 300 patients (approximately 150 patients per arm) will be enrolled for the 
purposes of regulatory registration to ensure at least 100 patients per arm with 1 year of exposure.  
Approximately 240 patients with EM will be rolled-over from Study CGAN. Approximately 
60 patients with CM will be enrolled.  
5.3.
End of Study Definition
End of the trial is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
The length of the 12-month treatment period is considered sufficient to assess the safety of a 
migraine prevention medication, and is consistent with regulatory requirements. A 4-month 
post-treatment follow-up period is included to evaluate patient safety during wash-out of 
galcanezumab.  This allows for a total of 5 months of observation from the time of the last 
injection of galcanezumab.  A 5-month, post-treatment, observation period allows for a wash-out 

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of approximately 5 elimination half-lives of galcanezumab, and should decrease galcanezumab
serum concentrations by approximately 97% during this time.
5.5.
Justification for Dose
Because a major part of Study CGAP is an extension of Study CGAN, the doses selected for 
Study CGAP were the same doses used in Study CGAN. A loading dose of galcanezumab
240 mg at Visit 3 will be used for patients who roll over from the placebo arm of Study CGAN 
to the 120 mg arm of Study CGAP. It will not be used for patients who roll over from the 
galcanezumab 120 mg arm of Study CGAN to the 120 mg arm of Study CGAP.  A loading dose 
of galcanezumab 240 mg will help patients achieve target serum concentrations of galcanezumab
to be consistent with the other treatment groups. In order to maintain the blinding of treatment 
groups in Study CGAN, 2 injections (galcanezumab and placebo) at Visit 3 of Study CGAP will 
be used for patients who roll over from the 120 mg arm of Study CGAN.

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6.
Study Population
Patients who complete the treatment period in Study CGAN will have an opportunity to roll over 
to study CGAP. Because the diagnosis is already confirmed at the enrollment of Study CGAN,
the patients are not needed to meet the definition of patients with EM used in Study CGAN to 
enter Study CGAP.
The definition of patients with EM which is used in Study CGAN is as follows:
[1] Patients are 18 to 65 years of age (inclusive) at the time of screening.
[2] Have a diagnosis of migraine as defined by International Headache Society (IHS) 
International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1 or
1.2) (HCCIHS 2013), with a history of migraine headaches of at least 1 year prior to 
Visit 1, and migraine onset prior to age 50.  
[3] Prior to Visit 1, have a history of 4 to 14 migraine headache days and at least 
2 migraine attacks per month, on average, within the past 3 months.
[4] From Visit 2 to Visit 3 (prospective baseline period), have a frequency of 4 to 
14 migraine headache days and at least 2 migraine attacks per month.
Eligibility of patients for study enrollment will be based on the results of clinical laboratory tests, 
and ECGs, as shown below. Study participants should be instructed not to donate blood or blood 
products during the study or for 5 months following last administration of investigational 
product.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria
prior to enrollment:
Patient and Disease Characteristics
[1]
Patients completed the treatment period of Study CGAN
Informed Consent and Patient Agreements
[2]
Patients are able and willing to give signed informed consent, and in the case 
of patients under 20 years old, informed consent signed by a parent or 
guardian.
[3]
Patients are reliable and willing to follow study procedures, including all 
follow-up visits.
[4]
Women of child-bearing potential must test negative for pregnancy based on 
urine pregnancy test kit. Women of non-childbearing potential are defined as 
follows:

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1)
Confirmed spontaneous amenorrhea with evidence of cessation of menses 
for at least 12 months and a follicle-stimulating hormone (FSH) level 
>40 mIU/mL at Visit 3
Or
2)
Confirmed from medical record to be infertile due to congenital or 
acquired condition (i.e. hysterectomy or bilateral oophorectomy),
Or
3)
Confirmed that all partners have had a vasectomy or tubal ligation AND 
have no fertile sperm based on multiple semen examinations, as shown by 
their medical record.  
Note: the urine pregnancy test result at Visit 3 should be used for the 
confirmation of eligibility at Visit 3; the serum pregnancy test result at 
Visit 3 should be used for the confirmation of continuation of the study,
and must be negative.
[5]
All patients must agree to use a reliable method of birth control during the 
study, as well as for 5 months after the last dose of investigational product.  
Acceptable methods of birth control for this study are 1) combination of 
condom and oral contraceptives, 2) combination of condom and hormonal 
releasing intrauterine system (IUS), or 3) combination of condom and copper 
intrauterine device (IUD).  These contraception methods are not required for 
female patients of non-childbearing potential, defined in inclusion criterion 
[4], or for male patients who meet the criterion defined in definition 3) of 
inclusion criterion [4].
[6]
Agree not to post any personal medical data related to the study or 
information related to the study on any website or social media site (eg, 
Facebook, Twitter, LINE, Mixi, etc.) until the entire trial has completed.
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria prior 
to enrollment:
Prior/Concomitant Therapy
[7]
Patients who are taking, or are expected to take, therapeutic antibodies
(including chimeric antibodies; eg, adalimumab, infliximab, trastuzumab, 
bevacizumab, etc.) other than galcanezumab.
Diagnostics Assessments
[8]
Patients with a history of head or neck injury during study CGAN.
[9]
Patients with a history of traumatic head injury associated with significant 
change in the quality or frequency of their headaches.
Medical Conditions

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[10] Patient who have ECGs showing abnormalities compatible with acute 
cardiovascular events and/or serious cardiovascular risk, including, but not 
limited to, a Fridericia’s corrected QT interval(QTcF) > 470 msec for women 
and >450 for men, or have had myocardial infarction, unstable angina, 
percutaneous coronary intervention, coronary artery bypass graft, stroke, or 
deep vein thrombosis/pulmonary embolism during Study CGAN, or have 
planned cardiovascular surgery or percutaneous coronary angioplasty.
[11] Any liver tests outside the normal range during Study CGAN that are 
clinically significant. Alanine aminotransferase (ALT) >2X the upper limit of 
normal (ULN), or total bilirubin (TBL) >1.5X ULN, or alkaline phosphatase 
(ALP) >2X ULN must be discussed and judged not clinically significant by 
Lilly Medical prior to enrollment.
[12] Patients who, in the clinician’s judgment, are actively suicidal and, therefore,
deemed to be at significant risk for suicide, or those who have answered “yes” 
to either Question 4 (Active Suicidal Ideation with Some Intent to Act, 
Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific 
Plan and Intent) on the “Suicidal Ideation” portion of the Columbia–Suicide 
Severity Rating Scale (C-SSRS), or answer “yes” to any of the suicide-related 
behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory 
act or behavior) on the “Suicidal Behavior” portion of the C-SSRS; and the 
ideation or behavior occurred within the past month. 
[13] Women who are pregnant or nursing.
[14] Patients with a history of drug or alcohol abuse/dependence during Study 
CGAN (excessive or compulsive use, as judged by the investigator), or 
currently using drugs of abuse (including opioids, barbiturates, and 
marijuana), or any prescribed or over-the-counter medication in a manner that 
the investigator considers indicative of abuse/dependence.
[15] Patients who have a history or presence of any other medical illness including,
but not limited to, any autoimmune disorder, cardiovascular, hepatic, 
respiratory, hematological, endocrine, psychiatric, or neurological disease, or 
any clinically significant laboratory abnormality that, in the judgment of the 
investigator, indicates a medical problem that would preclude study 
participation during Study CGAN.
Other Exclusions
[16] Patients who, in the opinion of the investigator, have other issues which would 
interfere with compliance with the study requirements and completion of 
evaluations required for this study.
[17] Patients who are investigator site personnel directly affiliated with this study 
and/or their immediate families.  Immediate family is defined as a spouse, 
parent, child, or sibling, whether biological or legally adopted.
[18] Patients who are Lilly employees.

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[19] Patients who are unwilling or unable to comply with the use of a paper diary 
and a data collection device.
[20] Patients who did not meet enrollment criteria and were inadvertently enrolled 
in Study CGAN 
6.3.
Lifestyle Restrictions
No changes in lifestyle or dietary requirements are required during the study.
6.4.
Screen Failures
The patients with EM who do not meet the criteria for participation in this study (screen failure) 
will not be rescreened. 

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7. Treatments
7.1.
Treatments Administered
This study involves galcanezumab (120 and 240 mg) administered once monthly.  The study 
drug (galcanezumab) will be administered by subcutaneous injections at 12 office visits during 
the treatment period (Section 2).  Table CGAP.7.1. shows the treatment regimens.
Table CGAP.7.1.
Treatment Regimen
Assignment
Regimen
CGAN Treatment
CGAP Treatment
Dose at Visit 3
Dose at Visits 5-15
Galcanezumab 120 mg
Galcanezumab 120 mg
Galcanezumab 120 mg, 
subcutaneous
(1 injection of 120 mg and 
1 injection of placebo using 
prefilled syringes)
Galcanezumab 120 mg 
monthly, subcutaneous
(1 injection of 120 mg using 
prefilled syringes)
Galcanezumab 240 mg
Galcanezumab 240 mg
Galcanezumab 240 mg monthly, subcutaneous
(2 injections of 120 mg using prefilled syringes)
Galcanezumab placebo
Galcanezumab 120 mg
Galcanezumab 240 mg, 
subcutaneous
(2 injections of 120 mg 
using prefilled syringes)
Galcanezumab 120 mg 
monthly, subcutaneous
(1 injection of 120 mg using 
prefilled syringes
Galcanezumab 240 mg
Galcanezumab 240 mg monthly, subcutaneous
(2 injections of 120 mg using prefilled syringes)
Injections will be administered by the investigator or patient.  If the patient is able to perform the 
injection, injection should be self-administered by the patient under the supervision of the 
investigator.
Possible injection sites include the abdomen, thigh, and upper arm.  Buttocks may also be used, 
if needed.
The investigator or his/her designee is responsible for the following:

Maintaining accurate records of investigational product dispensing and collection.

At the end of the study, returning all unused medication to Lilly, or its designee, unless 
the sponsor and sites have agreed that all unused medication is to be destroyed by the 
site, as allowed by local law.

Explaining the correct use of the investigational agent(s) to the patient, site personnel, 
and/or legal representative.

Verifying that instructions are followed properly.
7.1.1. Packaging and Labeling
Galcanezumab and placebo will be supplied as an injectable solution in 1-mL, single-dose, 
prefilled, disposable manual syringes with study-specific labels.  Each syringe of galcanezumab

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is designed to deliver 120 mg of galcanezumab.  In order to maintain the blind at Visit 3, the 
syringes (and contents) containing galcanezumab or placebo will be visibly indistinguishable 
from each other.  Syringes will be supplied in cartons, with the appropriate quantity of syringes 
specific to the planned dispensing schedule of investigational product.
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.1.2. Medical Devices
The medical devices provided for use in the study are prefilled syringes, which are not certified 
devices in Japan.
7.2.
Method of Treatment Assignment
Approximately 240 EM patients are planned to be rolled over from Study CGAN. If a patient 
meets all requirements for study eligibility, the patient will be administered 120 mg/month or 
240 mg/month.  
Patients who are in the galcanezumab treatment arms for Study CGAN continue with the same 
dose in Study CGAP, while patients who are in the placebo arm in Study CGAN are randomized 
to 120 mg or 240 mg at Visit 3 of Study CGAN (randomization ratio = 1:1).  After the 
randomization, patients are assigned to 1 of the 4 arms:

LY120/LY120: Study CGAN 120 mg galcanezumab with a loading dose/Study CGAP 
120 mg galcanezumab with placebo injection for a loading dose

LY240/LY240: Study CGAN 240 mg galcanezumab/Study CGAP 240 mg
galcanezumab

PLA/LY120: Study CGAN placebo/Study CGAP 120 mg galcanezumab with a loading 
dose

PLA/LY240: Study CGAN placebo/Study CGAP 240 mg galcanezumab
Treatment assignments of CGAP (120 mg or 240 mg) will be disclosed to patients at Visit 5 of 
Study CGAP.
7.2.1. Selection and Timing of Doses
This is a fixed-dose study.  The actual time of all dose administrations will be recorded in the 
patient’s electronic case report form (eCRF).
7.3.
Blinding
This is an open-label study. However, dosing at Visit 3 is blinded for all patients.
To preserve blinding, information regarding the treatment arm in Study CGAN and a loading 
dose at Visit 3 in Study CGAP will not be disclosed to investigators or patients until the 
CGAN/CGAP database locks (including follow-up periods).
7.4.
Dosage Modification
Dose modifications are not permitted in this study.

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7.5.
Preparation/Handling/Storage/Accountability
Investigational product will be shipped (as prefilled syringes) to sites using cold chain 
transportation.  Investigational product must be stable, and stored in a refrigerator at 2ºC to 8ºC 
(35.6ºF to 46.4ºF).
Approximately 30 minutes prior to administration, the syringes should be removed from the 
storage area and allowed to equilibrate at ambient conditions.  The drug product should be kept 
away from direct exposure to bright light (such as sunlight) and hot surfaces until administration.
7.6.
Treatment Compliance
Investigators will be required to document the administration of investigational product in the 
eCRF.
Investigational product must be administered as indicated in the Schedule of Activities 
(Section 2).  If the investigator is unable to administer the investigational product in the allowed 
window, then the situation should be discussed with Lilly to determine if the patient may 
continue.
7.7.
Concomitant Therapy
The list of medications allowed or not allowed for the acute treatment of migraine, as well as
those prohibited for the prevention of migraine, is provided in the concomitant medication list in 
the concomitant medications study tool, along with all concomitant therapies allowed or not 
allowed during the study.  Note that there are some limitations regarding concomitant 
medications for the acute treatment of migraines during the study. Any changes in the list of 
allowed/not allowed medications will be communicated to investigators, and will not constitute a
protocol amendment.
7.8.
Treatment after the End of the Study
7.8.1. Continued Access
Galcanezumab will not be made available to patients after conclusion of the study.

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8.
Discontinuation Criteria
Patients who discontinue the study or investigational product during the treatment period (SPIII) 
should be scheduled for an early discontinuation visit, and encouraged to complete the follow-up 
period (SPIV).
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Study Treatment
Discontinuation of the investigational product for abnormal liver tests should be considered by 
the investigator when a patient meets one of the following conditions after consultation with the 
Lilly designated medical monitor:

ALT or aspartate aminotransferase (AST) >8X ULN

ALT or AST >5X ULN for more than 2 weeks

ALT or AST >3X ULN and TBL >2X ULN or prothrombin time >1.5X ULN

ALT or AST >3X ULN with the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALP >3X ULN

ALP >2.5X ULN and TBL >2X ULN

ALP >2.5 ULN with the appearance of fatigue, nausea, vomiting, right quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%)
8.1.2. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the sponsor Lilly Clinical Research 
Physician/Clinical Research Scientist (CRP/CRS) and the investigator to determine if the patient 
may continue in the study.  If both agree it is medically appropriate to continue, the investigator 
must obtain documented approval from the sponsor CRP/CRS to allow the inadvertently enrolled 
patient to continue in the study, with or without treatment with investigational product.
8.2.
Discontinuation from the Study
Some possible reasons that may lead to permanent discontinuation include:

Enrollment in any other clinical trial involving an investigational product, or enrollment 
in any other type of medical research judged not to be scientifically or medically 
compatible with this study

Participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

Investigator decision:

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o
The investigator decides that the patient should be discontinued from the study
o
If the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new agent

Subject Decision:
o
The patient requests to be withdrawn from the study

Sponsor Decision:
o
If Lilly judges it necessary for medical, safety, regulatory, or other reasons 
consistent with applicable laws, regulations, and GCP
Patients who discontinue the study early (SP III) will have end-of-study (ET) procedures 
performed, as shown in the Schedule of Activities (Section 2) and are requested to proceed into 
the post-treatment phase.
Patients who discontinue the study early (SP IV) will have end-of-study (ET) procedures 
performed, as shown in the Schedule of Activities (Section 2).
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits, and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit, or were otherwise 
unable to be followed up by the site.
8.4
Discontinuation of Study Sites
Study site participation may be discontinued if the sponsor, the investigator, or the ethical review 
board/institutional review board (ERB/IRB) of the study site judges it necessary for any reason.
8.5
Discontinuation of the Study
The study may be discontinued if the sponsor judges it necessary, for any reason.

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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Effectiveness Assessments
9.1.1. Primary Effectiveness Assessments
Not applicable.
9.1.2. Secondary Effectiveness Assessments
As this is an uncontrolled study, all efficacy measures represent measures of treatment
effectiveness or health outcomes. Migraine headache day will be defined to include both 
migraine and probable migraine days. Patients will be asked to use a paper diary to record 
headache symptoms, duration, and severity.  The use of the diary and of the electronic clinical 
outcome assessment (eCOA) system is described in the Data Capture System section of
Appendix 3.  
In addition, the following scales will be used for secondary effectiveness assessments, as
summarized below.
9.1.2.1.
Patient Global Impression of Severity
The Patient Global Impression of Severity (PGI-S) scale (Guy 1976) is a patient-rated instrument 
that measures baseline illness severity.  The PGI-S includes a range of possible responses, from 1 
(“normal, not at all ill”) to 7 (“extremely ill”).
9.1.2.2.
Patient Global Impression of Improvement
The Patient Global Impression of Improvement (PGI-I) scale (Guy 1976) is a patient-rated 
instrument that measures improvement of the patient’s symptoms.  It is a 7-point scale in which a 
score of 1 indicates the patient is “very much better,” a score of 4 indicates the patient has 
experienced “no change,” and a score of 7 indicates the patient is “very much worse.”
9.1.3. Appropriateness of Assessments
All safety and effectiveness assessments have been well documented, and are generally regarded 
as reliable, accurate, and relevant in this patient population.  This includes health outcomes 
measures considered to be appropriate for evaluating changes in quality of life, global 
functioning, and disability (Section 9.9).

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9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study,
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate healthcare option: 
AEs that are serious or, otherwise, medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record, via eCRF, the occurrence and nature of 
each patient’s preexisting condition(s), including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs. Investigators should record their assessment of the 
potential relatedness of each AE to protocol procedure or investigational product, via eCRF.
The investigator will interpret and document whether an AE has a reasonable possibility of being 
related to study treatment, or a study procedure, taking into account the disease, concomitant 
treatment, or pathologies.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF, clarifying, if possible, the circumstances 
leading to any dosage modifications, or discontinuations of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (ie, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

considered significant by the investigator for any other reason:  important medical 
events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious, based upon appropriate medical judgment.

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Although all AEs occurring after signing the ICF are recorded in the eCRF, SAE reporting 
begins after the patient has signed the ICF and has received investigational product.  However, if 
an SAE occurs after signing the ICF, but prior to receiving investigational product, it needs to be 
reported ONLY if it is considered reasonably possibly related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event, via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements, any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient summary eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
US 21 Code of Federal Regulations 312.32, European Union (EU) Clinical Trial Directive 
2001/20/EC, and the associated detailed guidances or national regulatory requirements in 
participating countries require the reporting of SUSARs. Lilly has procedures that will be 
followed for the recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.
9.2.1.2.
Adverse Event Monitoring with a Systematic Questionnaire 
The C-SSRS (Posner et al. 2011) captures the occurrence, severity, and frequency of suicide-
related thoughts and behaviors during the assessment period. The scale includes suggested 
questions to solicit the type of information needed to determine if a suicide-related thought or 
behavior occurred. The tool was developed by the Columbia group (Posner et al. 2011) to 
prospectively categorize suicide-related events.
Before administering the C-SSRS, study site personnel will question the patient about any 
change in the preexisting condition(s) and the occurrence and nature of any AEs.  Non-serious 
AEs obtained through the questionnaire are recorded and analyzed separately. Only serious AEs 
and AEs leading to discontinuation elicited through the C-SSRS are to be recorded as AEs via 
eCRF. Serious adverse events must be reported to Lilly or its designee within 24 hours as SAEs. 
Any suicidal behavior, or suicidal ideation per Items 4 or 5 (active suicidal ideation with some 
intent to act, either without specific plan or with specific plan and intent) would prompt referral 
of the patient to a mental health professional.

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9.2.2. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he/she has a complaint 
or problem with the investigational product (or drug delivery system such as a prefilled syringe) 
so that the situation can be assessed.
9.3.
Treatment of Overdose
No data are available at this stage of development.
9.4.
Safety
The primary objective of this study is to evaluate the long-term safety and tolerability of 
galcanezumab 120 mg/month or 240 mg/month in patients with migraine for 1 year of treatment.  
Safety assessments include the occurrence of AEs, and changes from baseline in vital signs, 
ECGs, and laboratory tests.
9.4.1. Vital Signs and Weight
Vital signs will include body temperature, blood pressure, and pulse.  Blood pressure and pulse 
will be measured, in triplicate, in the sitting position prior to blood draws and study drug 
administration (see Study Schedule of Activities [Section 2]). Patient weight will be measured 
according to the Schedule of Activities (Section 2). Any clinically significant findings from vital 
signs measurement that result in a diagnosis and that occur after the patient receives the first dose 
of study treatment should be reported to Lilly or its designee as an AE via eCRF.
9.4.2. Electrocardiograms
For each patient, a single 12-lead digital ECG will be collected according to the Schedule of 
Activities (Section 2).  Electrocardiograms will have a central overread, and should be recorded 
according to the study-specific recommendations included in the ECG manual.
Any clinically significant findings from ECGs that result in a diagnosis should be reported to 
Lilly or its designee as an AE via eCRF.
9.4.3. Laboratory Tests
For each patient, laboratory tests detailed in Appendix 2 should be conducted according to the 
Schedule of Activities (Section 2).
Any clinically significant findings from laboratory tests that result in a diagnosis should be 
reported to Lilly or its designee as an AE via eCRF.
In addition, an immunogenicity and pharmacokinetic (PK) serum sample will be collected, when 
possible, for any patient who experiences a potential systemic allergic/hypersensitivity reaction 
during the study as judged by the investigator.  This immunogenicity and PK serum sample 

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should be collected immediately or as soon as possible, taking into consideration the availability 
and well-being of the patient.  Exact date and time of the sample should be recorded on the 
laboratory requisition form.
9.4.4. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
Investigators are responsible for monitoring individual patient safety throughout the trial.  If a 
study patient/subject experiences elevated ALT ≥3X ULN, ALP ≥2X ULN, or elevated TBL 
≥2X ULN, clinical and laboratory monitoring should be initiated by the investigator.  Details for 
hepatic monitoring depend upon the severity and persistence of observed laboratory test 
abnormalities.  To ensure patient/subject safety and comply with regulatory guidance, the 
investigator is to consult with the Lilly CRP/CRS regarding collection of specific recommended 
clinical information and follow-up laboratory tests.  See Appendix 4.
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
of approximately 2.5 mL each will be collected to determine the serum concentrations of 
galcanezumab.
A maximum of 3 samples may be collected at additional time points during the study, if 
warranted and agreed upon between both the investigator and sponsor.  Instructions for the 
collection and handling of blood samples will be provided by the sponsor.  
When a blood sample is collected, the time and date of last-dose administration prior to blood 
sampling should be recorded.  The actual date and time (24-hour clock time) of each sampling 
will be recorded.  To maintain the blinding in study CGAN, galcanezumab concentration
information will not be disclosed to either the investigators or the patients until the 
CGAN/CGAP database locks, including follow-up periods.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.
A validated assay will be used to determine serum galcanezumab concentrations.  Samples will 
be analyzed at a laboratory approved by the sponsor.
9.6.
Pharmacodynamics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine the plasma concentrations of CGRP. A maximum of 3 samples 
may be collected at additional time points during the study, if warranted and agreed upon 
between both the investigator and sponsor.  Instructions for the collection and handling of blood 
samples will be provided by the sponsor.  When a blood sample is collected, the time and date of 
last dose administration prior to blood sampling should be recorded.  The actual date and time 
(24-hour clock time) of each sampling will be recorded.

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A validated galcanezumab-tolerant assay will be used to determine plasma CGRP 
concentrations.  Samples will be analyzed at a laboratory approved by the sponsor.  To maintain 
the blinding in Study CGAN, CGRP concentrationinformation will not be disclosed to eitherthe
investigators or thepatients until the CGAN/CGAP database locks,including follow-up periods.
Bioanalytical samples collected to measure CGRP will be identified by the patient number 
(coded) and retained for a maximum of 1 year following last patient visit for the study at a 
facility selected by the sponsor.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.8. Biomarkers
Plasma and whole bloodRNA and epigeneticsamples for biomarker research will be collected at 
the timesspecified in the Schedule of Activities(Section 2)
CCI
where local regulations and ERBs
allow.
Samples will be used for research on the drug target, disease process, variable response to
galcanezumab, pathways associated with migraine headache and/or other pain conditions, 
CCI
CCI

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mechanism of action of galcanezumab, and/or research method, or in validating diagnostic tools 
or assay(s) related to migraine headache and/or other pain conditions.
All biomarker samples will be coded with the patient number.  These samples, and any data 
generated, can be linked back to the patient only by the investigator site personnel.  Samples will 
be destroyed according to a process consistent with local regulations.
Samples will be retained for a maximum 15 years after the last patient visit for the study, or for a 
shorter period if local regulations and ERBs impose shorter time limits, at a facility selected by 
the sponsor.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in drug 
development or when the drug is commercially available.
9.8.1. Samples for Immunogenicity Research
Where local regulations and ERBs allow, blood samples for immunogenicity testing will be 
collected to determine antibody production against galcanezumab as specified in the Schedule of 
Activities (Section 2).  Immunogenicity will be assessed by a validated assay designed to detect 
anti-drug antibodies (ADA) in the presence of the investigational product.  Antibodies may be 
further characterized and/or evaluated for their ability to neutralize the activity of galcanezumab.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if regulations and ERBs impose shorter time limits, at a facility selected by 
the sponsor.  The duration allows the sponsor to respond to future regulatory requests related to 
galcanezumab.
9.9.
Medical Resource Utilization and Health Economics
Health economic, disability, and quality-of-life assessments of galcanezumab in patients with 
migraine, except for Health Care Resource Utilization (HCRU), will be collected through the use 
of an eCOA system, as described in the Data Capture System section of Appendix 3.  The 
assessments will be based on the following scales:
Migraine Disability Assessment test (MIDAS):  The MIDAS was designed to quantify
headache-related disability over a 3-month period.  This instrument consists of 5 items that 
reflect the number of days reported as missing, or with reduced productivity, at work or home 
and social events; a higher value is indicative of more disability (Stewart 1999; Stewart 2001).  
This instrument is considered highly reliable and valid, and is correlated with clinical judgment 
regarding the need for medical care (Stewart et al. 1999; Stewart et al. 2001).
Migraine Specific Quality of Life questionnaire version 2.1 (MSQ v2.1):  The MSQ v2.1 is a 
self-administered health status instrument, and was developed to address physical and emotional 
limitations of specific concern to individuals suffering from migraine headaches.  The instrument 
consists of 14 items that address 3 domains:  (1) Role Function-Restrictive; (2) Role Function-
Preventive; and (3) Emotional Function (Jhingran et al. 1998).  The instrument was designed 
with a 4-week recall period, and is considered reliable, valid, and sensitive to change in migraine 

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(Jhingran et al. 1998; Rendas-Baum et al. 2013).  Clinically meaningful differences for each 
domain have been established, and are widely used in the literature.
Health Care Resource Utilization (HCRU) and Employment status:  The HCRU will be 
solicited by study personnel while documenting patient responses. The HCRU consists of 
3 questions, asking about hospital emergency room visits, overnight stays in a hospital, and any 
other visits with a healthcare professional that occurred since the patients’ last study visit. 
Patients are also specifically asked about the number of healthcare events that are related to 
migraine headaches, outside of visits associated with their participation in the clinical trial. The 
baseline visit will include the same questions, however, with the frame of reference being over 
the last 6 months.  A question on employment status is also solicited, given the correlation and 
potential confounding with health outcomes measures.
Participant Satisfaction with Medication Questionnaire-Modified (PSMQ-M): The 
PSMQ-M is a self-rated scale which measures patients’ levels of satisfaction with study 
medication (Kalali 1999). The scale has been modified for use in this study, assessing 3 items 
related to the clinical trial treatment over the past 4 weeks:  satisfaction, preference, and side 
effects.  Satisfaction responses range from “very unsatisfied” to “very satisfied” with the current 
treatment. Preference compares the current study medication to previous medications, with 
responses from “much rather prefer my previous medication” to “much rather prefer the 
medication administered to me during the study.”

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10. Statistical Considerations
10.1. Sample Size Determination
Approximately 300 patients (approximately 150 patients per arm; approximately 240 patients 
with EM and approximately 60 patients with CM) will be enrolled for the purposes of regulatory 
registration, to ensure at least 100 patients per arm with 1 year of exposure.  It is assumed that 
30% of patients will not complete a 12-month treatment period.
Approximately 240 EM patients will be rolled over from Study CGAN (120 patients for the 
CGAP 120-mg arm, 120 patients for the CGAP 240-mg arm).  
10.2. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
All Randomized Patients (ARP)
All patients who are randomized
Intent-to-Treat (ITT) Population
All patients who are assigned to a treatment and received at least 1 dose of study 
drug. Patients in the ITT population will be analyzed according to the treatment 
to which they were assigned.  Unless otherwise specified, the ITT population 
will be the primary population on which statistical analysis will be performed. 
Post-treatment Population
All patients who entered the follow-up period (SPIV) as indicated by entering 
any post-treatment visit.
Per Protocol Set (PPS)
Population
All patients in the ITT population who have no important protocol deviation 
which impact effectiveness analysis. Details will be specified in SAP.
Abbreviations:  SPIV = Study Period IV.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. Details of
statistical analysis methods will be described in the statistical analysis plan (SAP) document.
Unless otherwise specified, safety and effectiveness analyses will be conducted on an intent-to-
treat (ITT) basis, which is to include all patients who receive at least 1 dose of study drug. When 
change from baseline is assessed, the patient will be included in the analysis only if he/she has a 
baseline and a post-baseline measurement.
All statistical tests will be conducted at a 2-sided alpha level of 0.05, and 95% confidence
intervals will be provided, if appropriate. No adjustments for multiplicity will be applied to any 
safety or effectiveness analyses.
Unless specified otherwise, data for the patients with EM in Study CGAP will be reported by the 
treatment groups described in Section 7.2.
For EM patients’ analysis, baseline is Study CGAP Visit 3 (Study CGAN Visit 12) assessment,
unless otherwise specified with some exception (eg, immunogenicity analysis).

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If baseline data is not available at Study CGAP Visit 3 (eg, height), then baseline assessment of 
CGAN will be used.
Continuous safety and effectiveness variables will be summarized at each visit for observed 
measures (no imputation), and for change from baseline by each treatment group. If change 
from baseline is analyzed, then t-test may be used for each treatment group separately.
Categorical safety and effectiveness variables will be summarized at each visit for observed case. 
Any change to the data analysis methods described in the protocol will require an amendment
ONLY if it changes a principal feature of the protocol. Any other change to the data analysis
methods described in the protocol, and the justification for making the change, will be described
in the clinical study report (CSR). Additional exploratory analyses of the data will be conducted,
as deemed appropriate.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
The number and percentage of ITT patients who complete the study or discontinue early will be 
summarized for the open-label treatment phase (Study Period III) and post-treatment follow-up 
phase (Study Period IV), both overall and by visit. 
10.3.2.2. Patient Characteristics
The following patient characteristics at baseline will be summarized by treatment group for all 
ITT patients:  

Demographic (age, gender, ethnic origin, height, weight, waist/hip circumference)

Migraine headache, headache days

Alcohol, tobacco, caffeine, and nicotine consumption

Medical history and preexisting conditions
Medical history and preexisting conditions will be summarized by preferred term within system 
organ class (SOC).
10.3.2.3. Concomitant Therapy
The proportion of patients who received concomitant medication (as recorded via eCRF), as well 
as abortive medications (recorded through paper diary), will be summarized for all ITT patients 
for Study Periods III and IV, separately.
10.3.2.4. Treatment Compliance
Not applicable.

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10.3.3. Primary and Secondary Analyses
10.3.3.1. Primary Analyses
The primary objective of this study is to evaluate the long-term safety and tolerability of 
galcanezumab (120 or 240 mg/month) in patients suffering from migraine, for up to 1 year of 
treatment.
The safety and tolerability of treatment will be assessed by summarizing the following:

adverse events
o
treatment-emergent adverse events (TEAEs)

by preferred term

by SOC

by maximum severity 

considered to be related to investigational product by investigator
o
serious adverse events (SAEs)
o
adverse events leading to discontinuation
o
Follow-up-emergent adverse events (FEAEs)

suicidal ideation and behaviors assessed by solicited questioning using the 
C-SSRS

vital signs and weight

electrocardiograms (ECGs)

laboratory measurements

anti-galcanezumab antibodies
10.3.3.2. Secondary Analyses
10.3.3.2.1.Effectiveness Analyses
The effectiveness objective is to evaluate the effectiveness of galcanezumab in the prevention of 
migraine, using the following measures: 

mean change from baseline in the number of migraine headache days

mean change from baseline in the number of headache days

the proportion of patients meeting criteria for reductions of at least 30%, 50%, 
75%, or 100% in the number of migraine headache days

mean change from baseline in the frequency of medication use for the acute 
treatment of migraines or headaches

mean change from baseline in patient’s global impression of illness as measured 
by PGI-Severity 

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patient’s global impression of improvementas measured by PGI-Improvement 
postbaseline
mean change from baseline in the number of monthly migraine headache days or 
headache days requiring medication for the acute treatment of migraine headache 
or headache
mean change from baseline in the number of monthly migraine headache days 
requiring medication for the acute treatment of migraine headache
time to first loss of response (when patient no longer meets 50% response criteria 
and/or starts treatment using migraine prevention medication) during the follow-
up phase
10.3.4.Tertiary/Exploratory Analyses
Not applicable.
10.3.5.Other Safety Analyses
10.3.5.1.ImmunogenicityAnalyses
To evaluate the changes in immunogenicity data (ADA, neutralizing ADA) after treatment, the 
followingstatistical analyses are planned:
To summarize the proportions of positive results at each sample collection time 
point. 
To summarize the incidence of treatment-emergent immunogenicity for the open-
label treatment phase.  Treatment-emergent immunogenicity will be defined as 
any of the following:
o Anegative baseline result and a positive postbaseline ADAresult with a titer 
≥20.  This is alsocalled treatment-induced ADA. 
o Apositive baseline result and a positive postbaseline ADA result with a 
≥4-fold increase in titers (eg, baseline titer of 10 increasing to ≥40 
postbaseline).  This is called treatment-boosted ADA.

CCI
To summarize the onset of treatment-induced ADA. Anti-drug antibodyonset is 
defined as the time period between the initial administration of the study drug and 
the first instance of treatment-induced ADA.
 
 
 
 
 
 

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10.3.7. Other Analyses
10.3.7.1. Medical Resource Utilization and Health Economics
Change from baseline to each postbaseline visit for open-label treatment phase for MSQ v2.1
(including Role Function-Restrictive, Role Function-Preventive, Emotional Function, and total 
score) and MIDAS (item scores and total score) (Section 9.9) will be summarized.
The HCRU and PSMQ-M will be analyzed with details documented in the SAP. 
10.3.8. Interim Analyses
A data monitoring committee (DMC) is not planned for this study.
At least 1 interim analysis is planned after the database lock for Study CGAN. The interim 
analysis will be conducted to support regulatory submission prior to all patients completing the 
CGAP study.  The details of interim analysis will be described in the SAP.

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11.
References
Buse DC, Manack AN, Fanning KM, Serrano D, Reed ML, Turkel CC, Lipton RB. Chronic 
migraine prevalence, disability, and sociodemographic factors: results from the American 
Migraine Prevalence and Prevention Study. Headache. 2012;52(10):1456-1470.
Cernuda-Morollón E, Larrosa D, Ramón C, Vega J, Martínez-Camblor P, Pascual J. Interictal 
increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 
2013;81(14):1191-1196.
Guy W. ECDEU assessment manual for psychopharmacology, revised 1976. Rockville, MD: 
National Institute of Mental Health, Psychopharmacology Research Branch. p 217-222. 
Available at: https://archive.org/details/ecdeuassessmentm1933guyw. Accessed 27 July 2015.
Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X, Lines C, Edvinsson L, 
Goadsby PJ, Michelson D. Randomized controlled trial of the CGRP receptor antagonist 
telcagepant for migraine prevention. Neurology. 2014;83(11):958-966.
[HCCIHS]. Headache Classification Committee of the International Headache Society (IHS). 
The International Classification of Headache Disorders, 3rd edition (beta version). 
Cephalalgia. 2013;33(9):629-808.
Jhingran P, Osterhaus JT, Miller DW, Lee JT, Kirchdoerfer L. Development and validation of 
the Migraine-Specific Quality of Life Questionnaire. Headache. 1998;38(4):295-302.
Kalali A. Patient satisfaction with, and acceptability of, atypical antipsychotics. Curr Med Res 
Opin. 1999;15(2):135-137.
Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a 
causative role in migraine. Cephalalgia. 2002;22(1):54-61.
Peroutka SJ. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and 
challenges in treating headache. BioDrugs. 2014;28(3):237-244.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin 
GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial 
validity and internal consistency findings from three multisite studies with adolescents and 
adults. Am J Psychiatry. 2011;168(12):1266-1277.
Rendas-Baum R, Bloudek LM, Maglinte GA, Varon SF. The psychometric properties of the 
Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) in chronic migraine 
patients. Qual Life Res. 2013;22(5):1123–1133.
Sakai F, Igarashi H. Prevalence of migraine in Japan: a nationwide survey. Cephalalgia.
1997;17(1):15-22.
Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine 
Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. 
Neurology. 2001;56(6 Suppl 1):S20–S28. [Abstract]

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Stewart WF, Lipton RB, Kolodner K, Liberman J, Sawyer J. Reliability of the migraine 
disability assessment score in a population-based sample of headache sufferers. Cephalalgia.
1999;19(2):107-114.
Takeshima T, Ishizaki K, Fukuhara Y, Ijiri T, Kusumi M, Wakutani Y, Mori M, Kawashima M, 
Kowa H, Adachi Y, Urakami K, Nakashima K. Population-based door-to-door survey of 
migraine in Japan: the Daisen study. Headache. 2004;44(1):8-19.

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
ADA
Anti-drug antibodies
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CGRP
calcitonin gene-related peptide
CIOMS
Council for International Organizations of Medical Sciences
CM
chronic migraine
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
CRP/CRS
Lilly Clinical Research Physician/Clinical Research Scientist: Individual responsible 
for the medical conduct of the study.  Responsibilities of the CRP/CRS may be 
performed by a physician, clinical research scientist, global safety physician or other 
medical officer.
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
DMC
Data Monitoring Committee
ECG
electrocardiogram
eCOA
electronic clinical outcome assessment
eCRF
electronic case report form
EM
episodic migraine
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are 
those who have been assigned to a treatment.

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LY2951742 (galcanezumab)
Term
Definition
enter
Patients entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ePRO
electronic patient-reported outcomes
ERB
ethical review board
ET
early termination
EU
European Union
FEAE
follow-up-emergent adverse event
FSH
follicle-stimulating hormone
GCP
good clinical practice
HCRU
Health Care Resource Utilization
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonization
ICHD
International Classification of Headache Disorders
IHS
International Headache Society
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
institutional review board
ITT
intent to treat:  The principle that asserts that the effect of a treatment policy can be best 
assessed by evaluating on the basis of the intention to treat a patient (ie, the planned 
treatment regimen) rather than the actual treatment given.  It has the consequence that 
patients allocated to a treatment group should be followed up, assessed, and analyzed as 
members of that group irrespective of their compliance to the planned course of 
treatment.
IUD
intrauterine device
IUS
intrauterine system
MIDAS
Migraine Disability Assessment Test
MSQ v2.1
Migraine Specific Quality of Life Questionnaire version 2.1

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Term
Definition
PGI-I
Patient Global Impression of Improvement
PGI-S
Patient Global Impression of Severity
PK
pharmacokinetic(s)
PPS
per protocol set:  The set of data generated by the subset of patients who sufficiently 
complied with the protocol to ensure that these data would be likely to exhibit the 
effects of treatment, according to the underlying scientific model.
PSMQ-M
Patient Satisfaction with Medication Questionnaire-Modified
QTcF
Fridericia’s corrected QT interval
SAE
serious adverse event
SAP
statistical analysis plan
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SOC
system organ class
SP
study period
SUSARs
suspected unexpected serious adverse reactions
TBL
total bilirubin
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which and does not necessarily have to have a causal 
relationship with this treatment.
ULN
upper limit of normal
US
United States

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Appendix 2.
Clinical Laboratory Tests 
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume
Total bilirubin
Mean cell hemoglobin concentration
Direct bilirubin
Leukocytes (WBC)
Alkaline phosphatase
Neutrophils, segmented
Alanine aminotransferase (ALT)
Lymphocytes
Aspartate aminotransferase (AST)
Monocytes
Blood urea nitrogen (BUN)
Eosinophils
Creatinine
Basophils
Uric acid
Platelets
Calcium
Glucose
Albumin
Urinalysis
Creatine kinase (CK)
Specific gravity
Triglycerides
pH
Total cholesterol
Protein
HDL
Glucose
Ketones
Blood
HbA1c
Urine leukocyte esterase
a
Microscopic analysisa
Other
Urine culture
a
PK sample (galcanezumabserum concentration 
determination)
Immunogenicity
Pregnancy Test(females only)
b
Serum pregnancy or FSH
Urine pregnancy test (performed by site)
Stored Samples
Biomarker storage
(CM patients only)
RNA/Epigenetic
Abbreviations:  CGRP = calcitonin gene-related peptide;CM = chronic migraine;DNA = deoxyribonucleic acid; 
FSH = follicle-stimulating hormone; HbA1c = glycated hemoglobin; HDL = high density lipoprotein; PK = 
pharmacokinetic; RBC= red blood cells; RNA = ribonucleic acid; WBC = white blood cell.
a A positive urine leukocyte esterase result will require a follow-up sample with microscopic analysis and possibly 
a urine culture.
b
CCI
May be repeated during the study at the discretion of the investigator.
CCI

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Appendix 3.
Study Governance Considerations

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Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for ensuring:

that the patient understands the potential risks and benefits of participating in 
the study

that informed consent is given by each patient or legal representative.  This 
includes obtaining the appropriate signatures and dates on the informed 
consent form (ICF) prior to the performance of any protocol procedures and 
prior to the administration of investigational product.

answering any questions the patient may have throughout the study and 
sharing in a timely manner any new information that may be relevant to the
patient’s willingness to continue his or her participation in the trial.
Appendix 3.1.2.
Ethical Review
The investigator must give assurance that the ethical review board (ERB) was properly 
constituted and convened as required by International Conference on Harmonization (ICH)
guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s). All ICFs 
must be compliant with the ICH guideline on good clinical practice (GCP).
The study site’s ERB(s) should be provided with the following:

the current Investigator’s Brochure (IB) and updates during the course of the 
study

informed consent form (ICF)

relevant curricula vitae
Appendix 3.1.3.
Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences (CIOMS) International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third-party organization (TPO).

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Appendix 3.1.4.
Investigator Information
General practitioners, neurologists, and physicians who are pain specialists will participate as 
investigators in this clinical trial.
Appendix 3.1.5.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his/her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page, and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.6.
Final Report Signature
The clinical study report (CSR) coordinating investigator will sign the final CSR for this study, 
indicating agreement that, to the best of his/her knowledge, the report accurately describes the 
conduct and results of the study.
An investigator selected by the study team will serve as the CSR coordinating investigator.  If 
this investigator is unable to fulfill this function, another investigator will be chosen by Lilly to 
serve as the CSR coordinating investigator.
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his/her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

Provide instructional material to the study sites, as appropriate.

Sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report 
forms (CRFs), and study procedures.

Make periodic visits to the study site.

Be available for consultation, and stay in contact with the study site personnel by 
mail, telephone, and/or fax.

Review and evaluate CRF data, and use standard computer edits to detect errors in 
data collection.

Conduct a quality review of the database.
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.

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The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
Any data for which paper documentation provided by the patient will serve as the source 
document will be identified and documented by each site in that site’s study file.  
An electronic data capture system will be used in this study. The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system. 
Some or all of a patient’s data will be directly entered into the electronic case report form 
(eCRF) at the time the information is obtained. In instances where direct data entry is not used, 
the site will maintain source documentation in the trial files, and the patient’s data will be 
transcribed into the eCRF. Any data for which the eCRF will serve as the source document, or 
any other data not entered directly into the eCRF, will be identified and documented by the site 
in the site’s trial file. For data handled by a data management TPO, eCRF data, and some or all 
data that are related will be managed and stored electronically in the TPO system. Subsequent to 
the final database lock, validated data will be transferred to the sponsor. For data handled 
internally, eCRF data and some or all data that are related will be managed by the sponsor and 
stored electronically in the sponsor’s system. 
In this study, patient migraine headache data will be collected using a paper-based headache 
diary (patient diary). Patient migraine headache data will be collected directly via electronic 
patient-reported outcome (ePRO) diary during CGAN from Visit 11 to Visit 12 and these ePRO 
diary data will be utilized as CGAP Visit 3 data. Patient-rated scales/questionnaires will be 
collected directly via an ePRO tablet device at each visit. Data entered into the electronic clinical 
outcome assessment (eCOA) system will serve as the source data.
If eCOA records are stored at a third-party site, investigator sites will have continuous access to 
the source documents during the study and will receive an archival copy at the end of the study 
for retention. 
Any data for which the eCOA instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file. 
Case report form data will be encoded and stored in a clinical trial database. 
Data managed by a central vendor, such as laboratory test data or electrocardiogram (ECG) data, 
will be stored electronically in the central vendor’s database system. Data will subsequently be 
transferred from the central vendor to the Lilly data warehouse. 
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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Appendix 4.
Hepatic Monitoring Tests for Treatment-
Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with Lilly or its designee (CRP/CRS).
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatinine
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalized 
ratio; RBC = red blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

PPD
Leo Document ID = 6bcbb402-def7-4f18-848a-7ef70981c456
Approver: 
Approval Date & Time: 02-Sep-2016 15:12:28 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 02-Sep-2016 15:40:37 GMT
Signature meaning: Approved
PPD