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 Addendum I5Q-JE-CGAP (1) 
 
 
A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 (Galcanezumab) in Japanese 
Patients with Migraine 
 
NCT02959190 
 
Approval Date: 2-Sep-2016 
 
 
 

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 1
LY2591742 (galcanezumab)
1. Protocol Addendum I5Q-JE-CGAP (1)
A Phase 3, Long-Term, Open-Label Safety Study of 
LY2951742 (Galcanezumab) in Japanese Patients with 
Migraine
Confidential Information
The information contained in this protocol addendum 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 
clinical investigation of galcanezumab, unless such persons are bound by a confidentiality 
agreement with Eli Lilly and Company or its subsidiaries.  This document and its associated 
attachments are subject to United States Freedom of Information Act (FOIA) Exemption 4. 
LY2951742 (galcanezumab)
This addendum is to be performed in addition to all procedures required by protocol 
I5Q-JE-CGAP or any subsequent amendments to that protocol.
Eli Lilly Japan K.K. in Japan
Hyogo, Japan
Protocol Addendum (1) Electronically Signed and Approved by Lilly on date provided 
below.
Approval Date: 02-Sep-2016 GMT

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 2
LY2591742 (galcanezumab)
2. Table of Contents
Protocol Addendum I5Q-JE-CGAP (1)
A Phase 3, Long-Term, Open-Label Safety Study of LY 
2951742 (galcanezumab) in Japanese Patients with Migraine
Section
Page
1.
Protocol Addendum I5Q-JE-CGAP (1) A Phase 3, Long-Term, 
Open-Label Safety Study of LY2951742 (Galcanezumab) in 
Japanese Patients with Migraine..........................................................................................1
2.
Table of Contents................................................................................................................2
3.
Rationale for Addendum .....................................................................................................5
4.
Protocol Additions ..............................................................................................................6

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 3
LY2591742 (galcanezumab)
List of Tables
Table
Page
Table CGAP(1).1.
Migraine Definition for Patients with Chronic Migraine ...........................10
Table CGAP(1).2.
Treatment Regimen for the patients with chronic migraine........................18

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 4
LY2591742 (galcanezumab)
List of Figures
Figure
Page
Figure CGAP(1).1.
Study design for patients with chronic migraine. .................................11

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 5
LY2591742 (galcanezumab)
3. Rationale for Addendum
Study I5Q-JE-CGAP (Study CGAP) is a multisite, randomized, long-term (1-year), two arms, 
open-label study.  This study will be evaluating the safety and effectiveness of galcanezumab
(120 mg/month and 240 mg/month) in the prevention of migraine headache. As shown in 
protocol I5Q-JE-CGAP (protocol CGAP), Japanese patients with episodic migraine (EM) will 
roll over from Study I5Q-JE-CGAN.  In addition to these patients with EM, Japanese patients 
with chronic migraine (CM) will be also enrolled in the study CGAP. The objective of this 
addendum is to evaluate safety and effectiveness of galcanezumab in Japanese patients with CM.  
Schedule of Activities, Objective and Endpoints, Study Design, Study Population, Treatments, 
and Statistical Consideration are described in this protocol addendum (1).

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 6
LY2591742 (galcanezumab)
4. Protocol Additions
The content below will apply to patients with CM enrolled in Study CGAP.  The rest of the parts
of the protocol should be referred to the main protocol.
2.
Schedule of Activities
This is for the patients with CM.
Study Period 
(SP)
SP I-
Screening
SP II-
Prospective 
Baseline
SP III – Treatment
SP IV –
Follow-
up
(Target) Interval 
(days) since 
previous visit
30-
45
14
16
30
30
30
30
30
30
30
30
30
30
30
60
60
Allowable range 
(days) between 
visits
3-45
30-40a
Interval 
allowance (days) 
compared from 
previous visit
±3
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Visit
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16/ 
ET
17
18/ 
ET
Month
0
(D14)
1
2
3
4
5
6
7
8
9
10
11
12
14
16
Assessments and Procedures
Informed consent
X
Inclusion/Exclusi
on
X
X
X
Demographics
X
Physical 
examinationb
X
Height
X
Weight
X
X
X
X
Waist and hip 
circumference
X
Medical history 
X
Pre-specified 
migraine history/ 
pre-therapy
X
Substance use 
X
Prior Therapy 
(Migraine 
Medication)
X
ECGc
X
X
X
X
X
Vital signs
d
X
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
X
X

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 7
LY2591742 (galcanezumab)
Study Period 
(SP)
SP I-
Screening
SP II-
Prospective 
Baseline
SP III – Treatment
SP IV –
Follow-
up
(Target) Interval 
(days) since 
previous visit
30-
45
14
16
30
30
30
30
30
30
30
30
30
30
30
60
60
Allowable range 
(days) between 
visits
3-45
30-40a
Interval 
allowance (days) 
compared from 
previous visit
±3
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Visit
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16/ 
ET
17
18/ 
ET
Month
0
(D14)
1
2
3
4
5
6
7
8
9
10
11
12
14
16
Concomitant 
medications
X
X
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
X
Paper-diary 
training to 
patients
X
Clinical Laboratory Tests and Sampling Schedules
Hematology
X
X
X
X
X
X
X
Clinical 
chemistry
X
X
X
X
X
X
X
HbA1c
X
X
X
X
Urinalysisf
X
X
X
X
X
Serum Pregnancy 
(for women of 
childbearing 
potential)g or 
FSH at Visit 1 
(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
Urine Drug 
Screening
X
Immunogenicity
h
X
X
X
X
X
X
X
X
X

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 8
LY2591742 (galcanezumab)
Study Period 
(SP)
SP I-
Screening
SP II-
Prospective 
Baseline
SP III – Treatment
SP IV –
Follow-
up
(Target) Interval 
(days) since 
previous visit
30-
45
14
16
30
30
30
30
30
30
30
30
30
30
30
60
60
Allowable range 
(days) between 
visits
3-45
30-40a
Interval 
allowance (days) 
compared from 
previous visit
±3
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Visit
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16/ 
ET
17
18/ 
ET
Month
0
(D14)
1
2
3
4
5
6
7
8
9
10
11
12
14
16
Biomarker 
storage sampleh
X
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
 
 
X
Whole blood 
RNA/epigenetic 
sample
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
X
X
CCI
CCI

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 9
LY2591742 (galcanezumab)
Abbreviations:  CGRP = Calcitonin-gene related peptide; CRP = Lilly Clinical Research Physician; CRS = Lilly 
Clinical Research Scientist; C-SSRS =  Columbia Suicide Severity Rating Scale; D14 = Day 14; DNA = 
deoxyribonucleic acid; ECG = electrocardiogram;  ET = early termination; FSH = follicle stimulating hormone; 
HbA1c  = glycated haemoglobin; HCRU = Health Care Resource Utilization; MIDAS = Migraine Disability 
Assessment test; MSQ (v2.1) = Migraine Specific Quality of Life Questionnaire; PGI-I = Patient Global 
Impression of Improvement; PGI-S = Patient Global Impression of Severity; PK = pharmacokinetics; 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.
Note:  Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and follow-up may 
be required with patients in consultation with the Lilly, or its designee (CRP/CRS). See Appendix 4 of the 
protocol 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 800 series as the visit designation.
a
The eligibility period of the prospective baseline assessment will last from 30 to 40 days.  Investigators and 
patients may have up to an additional 5 days to schedule their Visit 3 appointment (beyond the 40 days); 
however, eligibility will be based on the 30-40 day period.
b
Physical examinations at screening must include a neurological exam.
c
Electrocardiograms as single, 12-lead digital will be performed at Visit 1, Visit 3, Visit 10,Visit16, and Visit 18
or early termination.  Note:  The Visit 3 ECG 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.  For screening only, ECG results will be read locally.
d
Vital signs 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.
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
A positive urine test must be followed by a serum pregnancy test for confirmation.
h
Immunogenicity, Biomarker storage samples,
 PK sampling, and Whole blood 
RNA/epigenetic sample to 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 ET.  Immunogenicity and PK samples also may be collected 
in the event of a systemic allergic/hypersensitivity reaction (see Section 9.4.3 of the main protocol).  The timing 
of samples will be recorded.
i
Patients will receive injections of galcanezumab after all other visit procedures are completed.  Following the 
first dose at Visit 3, patients will be observed for at least 30 minutes at the site.  Following subsequent doses, 
patients will be observed for at least 30 minutes post-injection if they have a significant adverse event after the 
first injection 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 SHSU when applicable) will be completed at scheduled and unscheduled office 
visits.
4.
Objectives and Endpoints
Table CGAP(1).1 provides definitions for the terms referenced below.
CCI

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 10
LY2591742 (galcanezumab)
Table CGAP(1).1.
Migraine Definition for Patients with Chronic Migraine
Diagnosis
Definition/Criteria
Migraine headache (Only Patients with CM)
A headache, with or without aura, of ≥30 minutes
duration which meets criteria A and B or meets criterion 
C:
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
OR
C.
The headache is believed by the patient to be 
migraine at onset and is relieved by a triptan or 
ergot derivative
(Definition adapted from the IHS ICHD-3 beta)
Probable migraine headache (Only Patients with CM)
A headache missing 1 of the migraine features in the 
IHS ICHD-3 beta definition such that one feature in 
criteria A is missing or one feature in criteria B is 
missing; that is, 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.  It must not meet criterion C.
Abbreviations:  ICHD = International Classification of Headache Disorders; IHS= International Headache Society
5.
Study Design
5.1.
Overall Design
Figure CGAP(1).1 illustrates the study design for CM patients.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 11
LY2591742 (galcanezumab)
Figure CGAP(1).1.
Study design for patients with chronic migraine.
Study Period I (SPI):  The study and potential risks will be explained to the patient at Visit 1.  
The informed consent form (ICF) must be signed before any study procedures are performed.
Patients are required to discontinue all excluded medications or treatments for migraine 
prevention at least 30 days prior to Visit 2. Botulinum toxin A or B in the head or neck area 
must be discontinued at least 4 months prior to Visit 2.
The screening visit (Visit 1) will consist of a full clinical assessment, including a comprehensive 
medical evaluation documenting medical history, and a physical and neurological examination.  
Visit 1 will be complete when the last scheduled procedure of the screening assessment for the 
patient is completed.
Study Period II (SPII):  Qualified patients will enter Study Period II (prospective baseline) to 
determine their eligibility for the study and to establish baseline data for comparison of endpoints 
during open-label treatment period. 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.
To avoid biased reporting, patients must not be told the number of headache days or migraine 
headache days on which study qualification is based.
Study Period III (SPIII):  At Visit3, patients meeting all eligibility requirements will be 
randomized to receive galcanezumab 120 mg/month, or galcanezumab 240 mg/month in a 1:1 
ratio.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 12
LY2591742 (galcanezumab)
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 after the first injection 
and/or they are judged by the investigator to have risk of a significant adverse event after 
injection.
5.2.
Number of Participants
Approximately 60 patients with CM will be enrolled (30 patients per arm [120 mg arm or 
240 mg arm]).
5.4.
Scientific Rationale for Study Design
The length of the open-label treatment of galcanezumab for 1 year is considered sufficient to 
assess the consistent effectiveness and safety on the patients with CM in comparison to those on 
the patients with EM. A 4-month post-treatment follow-up phase 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 last injection of galcanezumab.  A 5-month post-treatment observation period allows 
for a wash-out 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
Doses of 120 mg and 240 mg administered once monthly were selected for the patients with CM 
in the global phase III study (Study CGAI) primarily on the basis of clinical efficacyand
pharmacokinetic/pharmacodynamic data fromthe phase 2 dose-ranging study, which enrolled
patients with EM (Study CGAB).  The same doses in patients with EM and CM are warranted 
because the basic pathophysiology of headache is analogous and the mechanism of action of 
galcanezumab is the same in both patient populations.  Also, the doses for current standard of care
medications are the same for patients with EM and CM. 
6.
Study Population
All CM patients who enter this study must meet the following selection criteria.  Eligibility of
patients for study enrollment will be based on the results of a screening medical history, physical
examination, neurologicalexamination, clinical laboratorytests, electrocardiograms (ECGs), and
migraine historyduring screening and the prospective baseline period, as described in the
Inclusion and Exclusion Criteria sections. The nature of any comorbid conditions present at the 
time of the physical examination and any pre-existing conditions must be documented.  
Individuals who do not meet the criteria for participation in this study(screen failure) for specific
reasons as outlined may be considered for re-screening once, with approval from Lilly Medical
(See Section 6.4 Screen Failures in this addendum).  Studyparticipants should be instructed not to
donate blood or blood products during the study or for 5 months following the last administration
of investigationalproduct.  Prospective approval of protocoldeviations to recruitment and
enrollment criteria, also known as protocolwaivers or exemptions, are not permitted.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 13
LY2591742 (galcanezumab)
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria at 
screening:
Patient and Disease Characteristics
[1]
Patients are 18 to 65 years of age (inclusive) at the time of screening.
[2]
Have a diagnosis of chronic migraine as defined by the IHS ICHD-3 beta 
guidelines (1.3) (ICHD-3 2013), that is, a headache occurring on 15 or more 
days per month for more than 3 months, which has the features of migraine 
headache on at least 8 days per month.
[3]
Migraine onset prior to age 50.
[4]
Prior to Visit 1, a history of at least 1 headache-free day per month for the past 
3 months
[5]
From Visit 2 to Visit 3 (prospective baseline period), have a frequency of at 
least 15 headache days, of which at least 8 must have the features of migraine 
headache (see definitions in Table CGAP(1).1). To avoid biased reporting, 
patients must not be told the number of migraine headache days on which 
study qualification is based.
[6]
From Visit 2 to Visit 3 (prospective baseline period), have at least one 
headache-free day.
[7]
From Visit 2 to Visit 3 (prospective baseline period), must achieve sufficient 
compliance with paper diary headache entries as demonstrated by completion 
of at least 80% of diary entries
[8]
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.
[9]
Are reliable and willing to follow study procedures, including all follow-up 
visit
[10] Women of childbearing potential must test negative for pregnancy at the time 
of enrollment, based on a serum pregnancy test.  Women of non-childbearing 
potential are defined as follows:
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 screening,
Or
2)
Confirmed from medical record to be infertile due to congenital or 
acquired condition (i.e. hysterectomy or bilateral oophorectomy),
Or

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 14
LY2591742 (galcanezumab)
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.
[11] 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 
[10], or for male patients who meet the criterion defined in definition 3) of 
inclusion criterion [10].
[12] 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 (for 
example, 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 at
screening:
Prior/Concurrent Clinical Trial Experience
[13] Are currently enrolled in any other clinical trial involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study.
[14] Have participated within the last 30 days or within 5 half-lives (whichever is 
longer) in a clinical trial involving an investigational product.  If the 
investigational product’s half-life is not known, 6 months should have passed 
prior to Visit 1.
[15] Current use or prior exposure to galcanezumab or other antibodies to CGRP or 
its receptor, including those who have previously completed or withdrawn 
from this study or any other study investigating antibodies to CGRP or its 
receptor.
[16] Have participated in SPI and/or SPII of Study CGAN.
Prior/Concomitant Therapy
[17] Patients who are taking, or are expected to take, therapeutic antibodies 
(including chimeric antibodies) during the course of the study (eg, 
adalimumab, infliximab, trastuzumab, bevacizumab, etc.).  Prior use of 
therapeutic antibodies (including chimeric antibodies), other than antibodies 
to CGRP or its receptor, is allowed if that use was more than 12 months prior 
to Visit 2.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 15
LY2591742 (galcanezumab)
[18] Known hypersensitivity to multiple drugs, monoclonal antibodies or other 
therapeutic proteins, or to galcanezumab and the excipients in the 
investigational product.
[19] Are currently receiving medication or other treatments for the prevention of 
migraine headaches.  Patients must have discontinued such treatment at least 
30 days prior to Visit 2.  Botulinum toxin A and B that has been administered 
in the head or neck area must be discontinued at least 4 months prior to Visit 2. 
[20] Failure to respond to 3 or more adequately dosed migraine preventive 
treatments from different classes (that is, maximum tolerated dose for at least 
2 months). Failure to respond due to tolerability issues is not considered a 
treatment failure. Migraine preventive treatments are defined as the drugs 
with a recommendation grade A or grade B in Table 1 of section II-3-2 in the 
Japanese Clinical Guideline of chronic headache 2013 and botulinum toxin A 
or B.
[21] History of persistent daily headache, cluster headache or migraine subtypes 
including hemiplegic (sporadic or familial) migraine, ophthalmoplegic 
migraine, and migraine with brainstem aura (basilar-type migraine) defined by 
IHS ICHD-3 beta.
[22] History of headache other than migraine, tension type headache, or medication 
overuse headache, as defined by IHS ICHD-3 beta within 3 months prior to 
randomization.
[23] History of head or neck injury within 6 months prior to Visit 1.
[24] Patients with a history of traumatic head injury associated with significant 
change in the quality or frequency of their headaches should be excluded.
Medical Conditions
[25] Have ECGs showing abnormalities compatible with acute cardiovascular 
events and/or serious cardiovascular risk, including but not limited to a 
corrected QT (QTcF [Fridericia’s]) interval >470 msec for women and 
>450 msec for men, or have had myocardial infarction, unstable angina, 
percutaneous coronary intervention, coronary artery bypass graft, or deep vein 
thrombosis/pulmonary embolism within 6 months of screening, or have 
planned cardiovascular surgery or percutaneous coronary angioplasty, or a 
lifetime history of stroke.
Diagnostics Assessments
[26] Patients with a body mass index ≥40 kg/m2.
[27] Any liver tests outside the normal range at Visit 1 that are clinically 
significant.  Alanine aminotransferase (ALT) >2X upper limit of normal 
(ULN), or total bilirubin level (TBL) >1.5X ULN, or alkaline phosphatase 
(ALP) >2X ULN must be discussed and judged not clinically significant by 
Lilly Medical prior to enrollment.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 16
LY2591742 (galcanezumab)
[28] Evidence of significant active or unstable psychiatric disease by medical 
history, such as bipolar disorder, schizophrenia, personality disorders, or other 
serious mood or anxiety disorders. Note:  Patients with major depressive 
disorder or generalized anxiety disorder whose disease state is considered 
stable and expected to remain stable throughout the course of the study, in the 
opinion of the investigator, may be considered for inclusion if they are not on 
excluded medications.
[29] 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. 
[30] Women who are pregnant or nursing.
[31] Patients who have used opioids or barbiturate containing analgesic >3X per 
month for the treatment of pain in more than 2 of the past 6 months (opioid 
administration in an emergency setting may be an exception).
[32] History of drug or alcohol abuse/dependence within 1 year prior to Visit 1
(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.
[33] Have a positive urine drug screen for any substances of abuse at Visit 1.
Note:  A retest is allowed if the urine drug screen is positive for any 
prescribed substance or if, in the judgment of the investigator, there is an 
acceptable explanation for the positive result. The results of the retest must be 
negative at or prior to Visit 2.
[34] Have a history or presence of any other medical illness including but not 
limited to any autoimmune disease, 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.
Other Exclusions
[35] 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.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 17
LY2591742 (galcanezumab)
[36] 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.
[37] Are Lilly employees.
[38] Are unwilling or unable to comply with the use of a data collection device.

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 18
LY2591742 (galcanezumab)
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be
considered for re-screen once, with approval from Lilly Medical for only the criteria shown
below.  The interval between screening and rescreening must be at least 45 days or longer if
required for the specified timeframes in the inclusion/exclusion criteria or concomitant
medication list. If rescreening is performed, the individual must sign a new ICF and will be
assigned a new identification number.

Inclusion criterion [1].  If patients are less than age 18 at time of informed consent, they may 
be rescreened if they reach age 18 during the study enrollment period.

Inclusion criterion [10]

Exclusion criterion [14]

Exclusion criterion [17]

Exclusion criterion [19]

Exclusion criterion [30]
Patients using a concomitant medication that requires a stable dose for a specific duration prior
to Visit 2 may be rescreened if additional time is needed to meet the duration requirement.
7.
Treatment
7.1.
Treatments Administered
Table CGAP(1).2 shows the treatment regimens for CM patients.
Table CGAP(1).2.
Treatment Regimen for the patients with chronic migraine
Assignment
Regimen
Dose at V3
Dose V5-15
galcanezumab
120 mg
galcanezumab 240 mg, 
subcutaneous
(2 injections of 120 mg 
using pre-filled syringe)
galcanezumab 120 mg 
monthly, subcutaneous
(1 injection of 120 mg using 
pre-filled syringe
galcanezumab
240 mg
galcanezumab 240 mg  monthly, subcutaneous
(2 injections of 120 mg using pre-filled syringe)
7.2.
Method of Treatment Assignment
Approximately 60 patients with CM will be enrolled. Thirty patients will be randomized to 
120 mg arm, and 30 patients to 240 mg arm (randomization ratio 1:1).  Therefore, after the 
randomization, CM patients will be assigned to one of two arms;
CM120:  Study CGAP 120 mg galcanezumab with loading dose
CM240:  Study CGAP 240 mg galcanezumab

I5Q-JE-CGAP (1) Clinical Protocol Addendum
Page 19
LY2591742 (galcanezumab)
10.
Statistical Considerations
10.1.
Sample Size Determination
Analysis of CM data:
Approximately 60 patients with CM will be enrolled (30 patients for the CGAP 120mg arm, 30 
patients for the CGAP 240mg arm).  It is assumed that 30% of patients will not complete a 12-
month treatment period.
10.3.
Statistical Analyses
10.3.1.
General Statistical Considerations
Unless specified otherwise, data for the patients with CM in Study CGAP will be reported by the 
following treatment groups;
1) CM120:  CM patients who are randomized to galcanezumab 120 mg in Study CGAP
2) CM240:  CM patients who are randomized to galcanezumab 240 mg in Study CGAP
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 one 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.  In principle, any statistical analysis will be 
performed in a descriptive manner due to limited sample size and open-label treatment.
For analysis for the patient with CM, baseline is Visit 3 assessment in Study CGAP unless 
otherwise specified.
Details will be described in the statistical analysis plan (SAP) document.

Leo Document ID = 0ccc690c-0f9f-4806-9a1c-e4139d2a9c50
Approver: 
Approval Date & Time: 02-Sep-2016 15:21:28 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 02-Sep-2016 15:45:03 GMT
Signature meaning: Approved
PPD
PPD