A Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 (Galcanezumab) in Japanese Patients With Episodic Migraine
Phase: PHASE2
Conditions: Migraine
Sponsor: Eli Lilly and Company

Protocol: I5Q-JE-CGAN(a)
A Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 (Galcanezumab) 
in Japanese Patients With Episodic Migraine
NCT02959177 
Approval Date: 30-Aug-2016

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Approval Date: 30-Aug-2016 GMT

I5Q-JE-CGAN(a) Clinical Protocol
Page 2
LY2951742 (galcanezumab)
Table of Contents
Section
Page
1.
Synopsis .............................................................................................................................8
2.
Schedule of Activities .......................................................................................................10
3.
Introduction ......................................................................................................................14
3.1.
Study Rationale............................................................................................................14
3.2.
Background..................................................................................................................14
3.3.
Benefit/Risk Assessment..............................................................................................16
4.
Objectives and Endpoints..................................................................................................17
5.
Study Design.....................................................................................................................22
5.1.
Overall Design .............................................................................................................22
5.2.
Number of Participants.................................................................................................24
5.3.
End-of-Study Definition...............................................................................................24
5.4.
Scientific Rationale for Study Design...........................................................................24
5.5.
Justification for Dose ...................................................................................................24
6.
Study Population...............................................................................................................26
6.1.
Inclusion Criteria..........................................................................................................26
6.2.
Exclusion Criteria ........................................................................................................27
6.3.
Lifestyle Restrictions....................................................................................................30
6.4.
Screen Failures.............................................................................................................30
7.
Treatments........................................................................................................................32
7.1.
Treatments Administered .............................................................................................32
7.1.1.
Packaging and Labeling .......................................................................................32
7.1.2.
Medical Devices...................................................................................................32
7.2.
Method of Treatment Assignment ................................................................................32
7.2.1.
Selection and Timing of Doses.............................................................................33
7.3.
Blinding .......................................................................................................................33
7.4.
Dosage Modification....................................................................................................33
7.5.
Preparation/Handling/Storage/Accountability...............................................................33
7.6.
Treatment Compliance .................................................................................................34
7.7.
Concomitant Therapy...................................................................................................34
7.8.
Treatment after the End of the Study............................................................................34
7.8.1.
Study Extensions..................................................................................................34
7.8.2.
Continued Access.................................................................................................34
8.
Discontinuation Criteria ....................................................................................................35

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 3
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
8. 1.
Di sc o nti n uatio n f r o m St u d y Treat me nt .........................................................................3 5
8. 1. 1.
P er m a ne nt Disc o nt i n uati on fr o m St u d y Treat me nt ...............................................3 5
8. 1. 2.
Di sc o nti n uatio n of  I na d verte ntl y Enr olle d Patie nts ...............................................3 5
8. 2.
Di sc o nti n uatio n f r o m t he St u d y....................................................................................3 5
8. 3.
L ost t o F oll o w -U p ........................................................................................................3 6
8. 4
Di sc o nti n uatio n of  St u d y Sit es .....................................................................................3 6
8. 5
Di sc o nti n uatio n of  t he St u d y........................................................................................3 6
9.
St u d y  Assess me nts a n d Pr oce d ures...................................................................................3 7
9. 1.
Efficac y Assess me nts ...................................................................................................3 7
9. 1. 1.
Pri mar y Efficac y  Assess me nts .............................................................................3 7
9. 1. 2.
Sec o n dar y  Efficac y Assess me nts..........................................................................3 7
9. 1. 2. 1.
P ati e nt Glo b al  I mpressi o n  of Se verit y.............................................................3 7
9. 1. 2. 2.
P ati e nt Glo b al  I mpressi o n  of I mpr o ve me nt .....................................................3 7
9. 1. 3.
A p pr o priate ness of Assess me nts ..........................................................................3 7
9. 2.
A d verse E ve nts ............................................................................................................3 8
9. 2. 1.
S eri o us A d verse E ve nts ........................................................................................3 8
9. 2. 1. 1.
S us pecte d U ne x pecte d Seri o us A d verse React i ons ..........................................3 9
9. 2. 1. 2.
A d verse E ve nt M o nit ori n g wit h a S yste mat ic 
Q uest i on naire ................................................................................................. 3 9
9. 2. 2.
C o m plai nt Ha n dli n g .............................................................................................4 0
9. 3.
Treat me nt of O ver d ose ................................................................................................. 4 0
9. 4.
S af et y ...........................................................................................................................4 0
9. 4. 1.
Electr ocar di o gra ms ..............................................................................................4 0
9. 4. 2.
Vi t al Si g ns a n d Wei g ht ........................................................................................4 0
9. 4. 3.
La b orat or y  Tests..................................................................................................4 0
9. 4. 4.
S af et y M o ni t ori n g ................................................................................................4 1
9. 8.
Bi o m ar kers ...................................................................................................................4 2
9. 8. 1.
S a m ples f or I m m u n o ge nicit y Researc h ................................................................. 4 3
9. 9.
Me dical Res o urce Utilizat i on a n d Healt h Ec o n o mics ...................................................4 3
1 0.
Stati stical C o nsi derati o ns ..................................................................................................4 5
1 0. 1.
S a m ple Si ze Deter mi nat i on ..........................................................................................4 5
1 0. 2.
P o p ul at i ons f or 
4 5
1 0. 3. 1.
Ge neral Statist ical C o nsi derat i ons ........................................................................4 5
C CI
C CI
C CI
C CI
C CI

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 4
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
1 0. 3. 2.
Treat me nt Gr o u p C o m para bilit y ...........................................................................4 6
1 0. 3. 2. 1.
P ati e nt Dis p ositio n ..........................................................................................4 6
1 0. 3. 2. 2.
P ati e nt C haracteristics ....................................................................................4 6
1 0. 3. 2. 3.
C o nc o mita nt T hera p y .....................................................................................4 7
1 0. 3. 2. 4.
Treat me nt C o m plia nce ....................................................................................4 7
1 0. 3. 2. 5.
Electr o nic Pat ient -Re p orte d O utc o me Diar y C o m plia nce ................................4 7
1 0. 3. 3.
Pri mar y a n d Sec o n dar y  A nal yses .........................................................................4 7
1 0. 3. 3. 1.
Pri mar y A nal yses ...........................................................................................4 7
1 0. 3. 3. 2.
Ke y Sec o n dar y  A nal yses................................................................................4 8
1 0. 3. 3. 3.
Ot her Sec o n dar y  a n d E x plor at or y  Efficac y A nal yses......................................4 8
1 0. 3. 4.
S af et y A nal yses ....................................................................................................4 8
1 0. 3. 4. 1.
Cate g orical Safet y V ari a bles ...........................................................................4 9
1 0. 3. 4. 2.
A d verse E ve nts ...............................................................................................4 9
1 0. 3. 4. 3.
S ui ci de-Relate d T h o u g hts a n d Be ha vi ors ........................................................4 9
1 0. 3. 4. 4.
Vi t al Sig ns a n d Wei g ht ...................................................................................5 0
1 0. 3. 4. 5.
Electr ocar di o gra m I nter vals a n d Heart Rate ....................................................5 0
1 0. 3. 4. 6.
La b orat or y  Tests.............................................................................................5 0
1 0. 3. 5.
P har mac o ki net ic/ P har mac o d y na mic A nal yses......................................................5 1
1 0. 3. 6.
Ot her A nal yses .....................................................................................................5 1
1 0. 3. 6 . 1.
Me dical Res o urce Utilizat i on a n d Healt h Ec o n o mics ......................................5 1
1 0. 3. 6. 2.
S u b gr o u p A nal yses .........................................................................................5 1
1 0. 3. 7.
I nteri m A nal yses ..................................................................................................5 3
1 1.
Refere nces ........................................................................................................................5 4
1 2.
A p pe n dices .......................................................................................................................5 6
C CI

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
List of Tables
Table
Page
Table CGAN.4.1.
Objectives and Endpoints .......................................................................17
Table CGAN.4.2.
Migraine and Headache Endpoint Definitions.........................................21
Table CGAN.10.1.
Populations for Analyses ........................................................................45
Table CGAN.10.2.
Definition of Subgroup Variables ...........................................................52

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
List of Figures
Figure
Page
Figure CGAN.5.1.
Illustration of study design for Study I5Q-JE-CGAN..............................22

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................57
Appendix 2.
Clinical Laboratory Tests........................................................................61
Appendix 3.
Study Governance Considerations ..........................................................62
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality ............66
Appendix 5.
Protocol Amendment I5Q-JE-CGAN(a) Summary:  A 
Randomized, Double-Blind, Placebo-Controlled Study of 
LY2951742 (Galcanezumab) in Japanese Patients with Episodic 
Migraine.................................................................................................67
   

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
1. Synopsis
Title of Study:
A Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 (galcanezumab) in Japanese Patients with 
Episodic Migraine
Rationale:
Study I5Q-JE-CGAN (CGAN) is intended to assess the efficacy and safety of galcanezumab compared to placebo in 
the prevention of migraine headache in Japanese patients suffering from episodic migraine (defined as 4 to14 migraine
headache days per month), with or without aura, during 6 months of treatment.
Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To test the hypothesis that at least 1 dose of galcanezumab
(120 or 240 mg/month) is superior to placebo in the prevention 
of migraine headache in patients with episodic migraine.
The overall mean change from baseline in the 
number of monthly migraine headache days 
during the 6-month, double-blind treatment phase
Key Secondary Objectives
Regardless of primary objective results, all comparisons in 
secondary objectives are galcanezumab 120 mg versus placebo
and galcanezumab 240 mg versus placebo. 

To compare galcanezumab with placebo with respect 
to 50% response rate

The proportion of patients with a reduction 
from baseline ≥50% in monthly migraine 
headache days during the 6-month, double-
blind treatment phase

To compare galcanezumab with placebo with respect 
to 75% response rate

The proportion of patients with a reduction 
from baseline ≥75% in monthly migraine 
headache days during the 6-month, double-
blind treatment phase

To compare galcanezumab with placebo with respect 
to 100% response rate.

The proportion of patients with a reduction 
from baseline equal to 100% in monthly 
migraine headache days during the 6-
month, double-blind treatment phase

To compare galcanezumab with placebo with respect 
to change in functioning

The mean change from baseline in the Role 
Function-Restrictive domain score of the 
MSQ v2.1 (average of Months 4, 5, and 6)

To compare galcanezumab with placebo with respect 
to change in use of acute (abortive) migraine treatment

The overall 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 during the 6-month,
double-blind treatment phase 

To compare galcanezumab with placebo with respect 
to change in global severity of the migraine condition

The mean change from baseline in the 
PGI-S score (average of Months 4, 5, and 6)
Abbreviation:  MSQ v2.1 = Migraine-Specific Quality of Life Questionnaire version 2.1; PGI-S = Patient Global Impression of Severity.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
Summary of Study Design:  
A multisite, randomized, double-blind, placebo-controlled bridging trial with 4 study periods in patients who meet 
International Classification of Headache Disorders- (ICHD-) 3beta criteria for a diagnosis of migraine, with or 
without aura, at Visit 1, and fulfill the criteria of episodic frequency (4 to 14 migraine headache days per month) 
during the baseline period. Patients who complete Study Period III of study CGAN may have an option to roll-over 
to the open-label extension study, I5Q-JE-CGAP (CGAP).  
Treatment Arms and Duration:  
Three treatment arms:  galcanezumab 120 mg/month with a 240 mg loading dose at the first injection; galcanezumab
240 mg/month; and placebo. Following a prospective baseline (30-40 days) period, eligible patients will be 
randomized in a 2:1:1 ratio to receive placebo, galcanezumab 120 mg/month with a 240 mg loading dose, and 
galcanezumab 240 mg/month, respectively, and will begin a 6-month treatment phase.  This phase will be followed 
by a 4-month, post-treatment phase during which patients will no longer receive any study drug.
Number of Patients:
The study will screen an estimated 902 potential study participants to ensure randomization of approximately 451 
(225, 113, 113) patients with episodic migraine.
Statistical Analysis:
Unless otherwise specified, the primary analyses will be conducted on an intent to treat (ITT) population, which 
includes all patients who are randomized and receive at least 1 dose of study product.  Patients in the ITT population 
will be analyzed according to the treatment arm to which they are randomized.  When mean change from baseline is 
assessed, the patient will be included in the analysis only if the patient has a baseline and post-baseline
measurement.  The primary analysis will evaluate the efficacy of 2 doses of galcanezumab compared with placebo 
on the overall mean change from baseline in the number of monthly migraine headache days during the 6-month,
double-blind treatment phase.  The primary analysis will be performed using a restricted-maximum, likelihood-
based mixed models repeated measures (MMRM) technique.  The analysis will include the fixed categorical effects 
of treatment, month, and treatment-by-month interaction, as well as the continuous fixed covariates of baseline 
number of migraine headache days and baseline number of migraine headache days-by-month interaction.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
2. Schedule of Activities
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
15
15
15
15
60
60
Allowable range 
(days) between visits
3-45 
30-40a
Interval allowance 
(days) compared 
from previous visit
± 1
± 3
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 5
± 5
Visit
1
2
3
4
b
5
6
7
8
9c
10
11c
12/ET
13
14/ET
Month
0
0.5
1
2
3
4
4.5
5
5.5
6
8
10
Informed consent
X
Inclusion/exclusion
X
X
X
Demographics
X
Physical 
examinationd
X
Height
X
Weight
X
X
X
Waist and hip 
circumference
X
Medical history 
X
Pre-specified 
migraine history
X
Substance use 
X
Prior Therapy 
(Migraine 
Medication)
X
ECG
e
X
X
X
X
Vital signsf
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
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO training
X
ePRO daily patient 
entriesg
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient training 
video
X
Hematology
X
X
X
X
X
Clinical chemistry
X
X
X
X
X

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 1 1
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
St u d y Peri o d ( S P)
S P I -
Scree ni n g
S P II -
Pr os pecti ve 
B aseli ne
S P III – Tre at me nt
S P I V –
F oll o w -u p
( T ar get) I nter v al 
( d a ys) si nce pre vi o us 
visit
3 0-
4 5
1 4 
1 6 
3 0 
3 0 
3 0 
1 5 
1 5 
1 5 
1 5 
6 0 
6 0
All o w a ble r a n ge 
( d a ys) bet wee n visits
3- 4 5 
3 0- 4 0 a
I nter v al all o w a nce 
( d a ys) co m p are d 
fr o m pre vi o us visit
± 1 
± 3 
± 2 
± 2 
± 2 
± 2
± 2 
± 2
± 2 
± 5 
± 5
Visit
1 
2 
3 
4
b
5 
6 
7 
8 
9 c
1 0 
1 1 c
1 2 / E T
1 3
1 4 / E T
M o nt h
0
0. 5
1 
2 
3 
4
4. 5
5
5. 5
6 
8 
1 0
H b A 1c
X
X
X
Uri nal ysis h
X
X
X
X
Ser u m Pre g na nc y 
(f or w o me n of 
c hil d beari n g 
p ote ntial) i or F S H at 
Visit 1 ( f or w o me n 
w h o ha ve e vi de nce 
of cessati o n of 
me nses f or at least 
1 2 m o nt hs )
X
X
X
Uri ne pre g na nc y i
X  
X  
X  
X  
X  
X  
X m
Uri ne dr u g scree n
X
I m m u n o ge nicit yj
X  
X  
X  
X  
X
X
X
Bi o mar ker st ora ge 
sa m ple
j
X  
X  
X
X  
X m
X
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
P K bl o o d sa m ple
j
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
 
 
X
W h ole bl o o d 
R N A/e pi ge netic 
sa m plej
X
X
X
St u d y  dr u g 
a d mi nistere d
k
X  
X  
X  
X  
X  
X
MI D A S
X
X
X
X
M S Q v 2. 1
X  
X  
X  
X  
X  
X  
X
X
P GI - S
X  
X  
X  
X  
X  
X  
X
X
P GI -I
X  
X  
X  
X  
X  
X
X
C CI
C CI

I5Q-JE-CGAN(a) Clinical Protocol
Page 12
LY2951742 (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
15
15
15
15
60
60
Allowable range 
(days) between visits
3-45 
30-40a
Interval allowance 
(days) compared 
from previous visit
± 1
± 3
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 5
± 5
Visit
1
2
3
4
b
5
6
7
8
9c
10
11c
12/ET
13
14/ET
Month
0
0.5
1
2
3
4
4.5
5
5.5
6
8
10
PSMQ-M
X
X
HCRU and 
Employment status
X
X
X
X
X
X
X
X
X
C-SSRS/SHSF, 
SHFUl
X
X
X
X
X
X
X
X
X
X
X
Abbreviations:  AE = adverse event; CGRP = Calcitonin-gene related peptide; CRP = Lilly Clinical Research 
Physician; CRS = Lilly Clinical Research Scientist; C-SSRS =  Columbia Suicide Severity Rating Scale;
DNA = deoxyribonucleic acid; ECG = electrocardiogram; ePRO = electronic patient-reported outcomes; 
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 Questionnaire; PGI-I = Patient Global Impression of Improvement; PGI-S = Patient Global 
Impression of Severity; PK = pharmacokinetics; PSMQ-M = Patient 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 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
Visit is to include a review of any spontaneously reported AE, concomitant medications and collection of blood 
samples for immunogenicity, PK, and CGRP plasma.
c
Visit is to include a review of any spontaneously reported AE, concomitant medications and collection of blood 
samples for PK, and CGRP plasma.
d
Physical examinations at screening must include a neurological exam.
e
Electrocardiograms as single, 12-lead digital will be performed at Visit 1, Visit 3, Visit 12, and Visit 14 or ET.  
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.
f
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.

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 1 3
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
g
Patie nt e n ter i nt o t he eP R O diar y t he occ urre nce of hea dac hes, hea dac he d urati o n, hea dac he feat ures, se verit y of 
hea dac he, a n d use of hea dac he me dicati o n
h
I n t he e ve nt of a p ositi ve uri ne le u k oc yte esterase res ult, a re peat uri ne sa m ple will be c ollecte d at t he ne xt visit 
a n d s hi p pe d t o t he ce ntral la b or at or y.
i
A p ositi ve uri ne test m ust be f oll o we d b y a ser u m pre g na nc y test f or c o nfir mati o n.
j
Bi o mar ker st ora ge sa m ple s, im m u n o ge nicit y, 
 P K sa m pli n g, a n d w h ole bl o o d 
R N A/e pi ge netic sa m ple t o be perf or me d at t he i n dicate d visits a n d pri or t o d ose a d mi nistrati o n if t he visit is a 
d osi n g visit.  Sa m ples will be ta ke n i n t he e ve nt of E T .  I m m u n o ge nicit y a n d P K sa m ples als o ma y be c ollecte d 
i n t he e ve nt of a s yste mic aller gic/ h y perse nsiti vit y reacti o n (see Secti o n 9. 4. 3 ).  T he ti mi n g of sa m ples will be 
rec or de d.
k
Patie nts will recei ve i njecti o ns of place b o or galca nez u ma b after all ot her visit pr oce d ures are c o m plete d.   
F oll o wi n g t he first d ose at Visit 3, patie nts will be o bser ve d f or at least 3 0 mi n utes at t he site. F oll o wi n g 
s u bse q ue nt d oses, patie nts will be o bser ve d f or at least 3 0 mi n utes p ost -i njecti o n if t he y h a ve a si g nifica nt 
a d verse e ve nt after t he first i njecti o n a n d/ or t he y are j u d ge d b y t he i n vesti gat or t o ha ve ris k of a si g nifica nt 
a d verse e ve nt after i njecti o n.
l
T he C -S S R S a n d S H S F (a n d S H S U , w h e n a p plica ble) will be c o m plete d at sc he d ule d a n d u nsc he d ule d off ice 
visits .
m
Ur i ne pre g na nc y a n d bi o mar ker st ora ge sa m ple are c ollecte d o nl y f or  patie nts r olli n g o ver t o St u d y C G A P.
C CI

I5Q-JE-CGAN(a) Clinical Protocol
Page 14
LY2951742 (galcanezumab)
3. Introduction
3.1.
Study Rationale
Study I5Q-JE-CGAN (CGAN) is intended to assess the efficacy and safety of galcanezumab 
compared to placebo in the prevention of migraine headache in Japanese patients suffering from 
episodic migraine (defined as 4 to14 migraine headache days per month), with or without aura, 
during 6 months of treatment.
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). Migraine is 
one of the most common diseases in Japanese middle-aged women (Nagai et al. 2015). More 
than 25% of Japanese patients with migraine suffer more than 3 headache days per month, which 
leads to a significant work disability. In addition, about 5.3% to 7.3% of those patients are 
continuously visiting doctors (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 when compared to loss of earnings from lost work days.
Migraine has 2 major subtypes: migraine with aura; and migraine without aura. Recurrent 
episodes of headache are a characteristic symptom shared by both migraine subtypes; therefore, 
they are collectively called as episodic migraine (EM). The frequency of headache episodes may 
worsen in the clinical course of EM. In addition to the acute treatment, preventive treatment 
options should be considered for severe and frequent EM. Currently, there are only 4 Food and 
Drug Administration- (FDA-) approved medications for migraine prevention. These are 
topiramate, divalproex sodium, timolol, and propranolol. In Japan, sodium valproate, 
propranolol, and lomerizine (a calcium channel blocker originally developed in Japan) are 
approved for the prevention of migraine. While these drugs have been shown to be fairly 
effective in some cases, not all patients respond to them. Moreover, the established adverse 
effect of valproate on fetuses has made clinicians reluctant to prescribe it for young female 
patients (Meador et al. 2012). New treatment options with improved efficacy and tolerability are 
needed for patients suffering from migraine headaches.
Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is widely expressed 
throughout the central and peripheral nervous systems, and acts as a local facilitator of 
inflammatory processes. Numerous lines of evidence implicate CGRP in the pathophysiology of 
migraine. These include increased levels of CGRP in the peripheral and cranial circulation 
during a migraine attack (Goadsby and Edvinsson 1990; Goadsby and Edvinsson 1993), 
normalization of increased CGRP levels following effective migraine treatment (Buzzi et al. 
1995; Fanciullacci et al. 1995), and efficacy of small-molecule CGRP antagonists in the acute 
treatment of migraine (Peroutka 2014) and the prevention of migraine (Ho et al. 2014).
Correspondingly, the neutralization of the CGRP signal with neutralizing antibodies has been 
shown to modulate neurogenic inflammation; thus, these antibodies may represent a promising 
therapeutic approach for the prevention of migraine.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
Galcanezumab is a humanized monoclonal antibody that potently and selectively binds to CGRP 
preventing CGRP-mediated biological effects. A single and multiple-dose ascending study 
(CGAA) in healthy subjects and a Phase 2a proof-of-concept study (ART-01) in patients with 
migraine have been completed. In study CGAA, galcanezumab was administered 
subcutaneously to human volunteers at single doses up to 600 mg, and repeatedly administered 
as 4 doses of 150 mg every other week.  This study demonstrated that galcanezumab was well-
tolerated and did not result in any serious adverse event (SAE) or treatment emergent adverse 
events (TEAEs). Study CGAE was conducted in 35 healthy Japanese and Caucasian subjects. 
The safety profile of galcanezumab in this study was consistent with that observed in Study 
CGAA. The most frequently reported adverse events (AEs) in galcanezumab-treated subjects 
were injection-related events, contact dermatitis (related to electrocardiogram [ECG] electrodes,
as noted by the investigator), and neck pain. Events were generally reported at an equivalent rate 
in Japanese and Caucasian subjects. 
In the proof-of-concept study, ART-01, galcanezumab was administered subcutaneously once 
every 14 days for 6 doses. Galcanezumab significantly reduced the number of migraine 
headache days compared to placebo (P=0.003) at the 12-week endpoint. Moreover, 
galcanezumab was statistically significantly better than placebo on all secondary efficacy 
endpoints.  The safety data of this study are consistent with the results of studies CGAA/CGAE. 
No patient treated with galcanezumab discontinued due to an AE. Ten SAEs were reported, in 
which 2 SAEs were reported by 2 patients treated with galcanezumab and 8 SAEs were reported 
by 4 placebo-treated patients. None of the SAEs was judged by the investigator as related to 
treatment. Treatment-emergent adverse events that were reported more often by galcanezumab-
treated patients than by placebo-treated patients were injection site pain (18 [17%] vs. 7 [6%]), 
upper respiratory tract infection (26 [24%] vs. 12 [11%]), abdominal pain (6 [6%] vs. 3 [3%]),
dizziness (5 [5%] vs. 3 [3%]), injection site erythema (5 [5%] vs. 0 [0%]), rash (5 [5%] vs. 0 
[0%]), and hypertension (5 [5%] vs. 0 [0%]). Galcanezumab did not cause any obvious changes 
in clinical chemistry or hematologic parameters, and there was no apparent effect on heart rate, 
blood pressure or ECG measurements (QT-interval or Fridericia’s corrected QT [QTcF] interval) 
(Dodick et al. 2014). 
The Phase 2b dose-ranging study, I5Q-MC-CGAB (CGAB), is a multisite, double-blind, 
randomized, placebo-controlled study of galcanezumab that was conducted in the US. This 
study aimed to assess the efficacy and safety of 4 doses of galcanezumab (5 mg, 50 mg, 120 mg, 
and 300 mg administered subcutaneously every 4 weeks over 12 weeks) in the prevention of 
migraine headache, compared to placebo, in outpatients suffering from EM. The primary 
endpoint (the effect on migraine headache days at least 1 galcanezumab dose superior to 
placebo) was successfully demonstrated. Based on the result of the CGAB study and the 
analysis on pharmacokinetic/pharmacodynamic (PK/PD) data, the dose range was optimized for 
Phase 3 studies (CGAG/CGAH for episodic migraine). The proposed study is a bridging study 
conducted in Japan aimed to confirm the safety and efficacy of galcanezumab in the prevention 
of migraine headache in Japan population. The study design of the proposed study is similar to 
CGAG/CGAH studies.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
3.3.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, SAEs and reasonably 
anticipated AEs of galcanezumab are to be found in the Investigator’s Brochure (IB).  

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 1 7
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
4.
O bj e cti v e s a n d E n d p oi nt s
Ta ble C G A N. 4. 1 s h o ws t he o bjecti ves a n d e n d p oi nts of t he st u d y.  Ta ble C G A N . 4. 2 pr o vi des 
defi nit i ons f or t he ter ms refere nce d bel o w.
T a bl e C G A N. 4 . 1.
O bj e cti v e s a n d E n d p oi nt s
O bjecti ves
E n d p oi nts
Pri m ar y
T o test t he h y p ot hesis t hat at least 1 d ose of 
galca nez u ma b ( 1 2 0 or 2 4 0 m g/ m o nt h) is s u peri or t o 
place b o i n t he pre ve nti o n of mi grai ne hea dac he i n 
patie nts wit h e pis o dic mi grai ne.
T he o verall mea n c ha n ge fr o m baseli ne i n t he 
n u m ber of m o nt hl y mi grai ne hea dac he da ys d uri n g 
t he 6-m o nt h , d o u ble -bli n d treat me nt p hase
Ke y Sec o n d ar y O bjecti ves
Re gar dless of pri mar y o bjecti ve res ults, all c o m paris o ns 
i n sec o n dar y o bjecti ves are galca nez u ma b 1 2 0 m g 
vers us place b o a n d galca nez u ma b 2 4 0 m g v s. place b o .

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o 5 0 % res p o nse rate

T he pr o p orti o n of patie nts wit h a re d ucti on 
fr o m baseli ne ≥5 0 % i n m o nt hl y mi grai ne 
hea dac he da ys d uri n g t he 6 -m o nt h , d o u ble -
bli n d treat me nt p hase

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o 7 5 % res p o nse rate

T he pr o p orti o n of patie nts wit h re d ucti on fr o m 
baseli ne ≥7 5 % i n m o nt hl y mi grai ne hea dac he 
da y s d uri n g t he 6-m o nt h , d o u ble -bli n d 
treat me nt p hase

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o 1 0 0 % res p o nse rate.

T he pr o p orti o n of patie nts wit h re d ucti o n fr o m 
baseli ne e q ual t o 1 0 0 % i n m o nt hl y mi grai ne 
hea dac he da ys d uri n g t he 6 -m o nt h d o u ble -bli n d 
treat me nt p hase

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o c ha n ge i n f u ncti o ni n g

T he mea n c ha n ge fr o m baseli ne i n t he R ole 
F u ncti o n -Restricti ve d o mai n sc ore of t he M S Q 
v 2. 1 (a vera ge of M o nt hs 4, 5, a n d 6)

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o c ha n ge i n use of ac ute (a b orti ve) 
mi grai ne treat me nt

T he o verall mea n c ha n ge fr o m baseli ne i n t he 
n u m ber of m o nt hl y mi grai ne hea dac he da ys or  
hea dac he da ys re q uiri n g me dicati o n f or t he 
ac ute treat me nt of mi grai ne h e a dac he or 
hea dac he d uri n g t he 6 -m o nt h , d o u ble -bli n d 
treat me nt p hase 

T o c o m pare galca nez u ma b wit h place b o wit h 
res pect t o c ha n ge i n gl o bal se verit y of t he 
mi grai ne c o n diti o n 

T he mea n c ha n ge fr o m baseli ne i n t he P GI- S 
sc ore (a vera ge of M o nt hs 4, 5, a n d 6 )
C CI

I5Q-JE-CGAN(a) Clinical Protocol
Page 18
LY2951742 (galcanezumab)
Other Secondary Objectives

To compare galcanezumab with placebo with 
respect to change in headache days

The overall mean change from baseline in the 
number of monthly headache days during the 
6-month, double-blind treatment phase

To compare galcanezumab with placebo with 
respect to change in moderate-to-severe 
headache days

The overall mean change from baseline in the 
number of monthly moderate to severe 
headache days during the 6-month, double-
blind treatment phase

To compare galcanezumab with placebo with 
respect to 30% response rate

The proportion of patients with reduction from
baseline ≥30% in monthly migraine headache 
days during the 6-month, double-blind 
treatment phase

To compare galcanezumab with placebo with 
respect to distribution of response rates

Cumulative distribution of monthly migraine
headache day response rates during the 
6-month, double-blind treatment phase

To compare galcanezumab with placebo with 
respect to time to 50% response

Time to first occurrence of a ≥50% reduction 
from baseline in the number of monthly 
migraine headache days (Kaplan-Meier 
analysis)

To compare galcanezumab with placebo with 
respect to onset of effect

The initial month at which statistical separation 
in mean change from baseline in the number of 
monthly migraine headache days is 
demonstrated and maintained at all subsequent 
months through Month 6

To compare galcanezumab with placebo with 
respect to onset of 50% sustained response

The initial month at which statistical separation 
in the proportion of patients meeting at least a 
50% reduction in monthly migraine headache 
days that is maintained at all subsequent 
months through Month 6

To compare galcanezumab with placebo with 
respect to maintenance of 50% response

The proportion of patients who maintain 50% 
response criteria for at least 3 consecutive 
months to the patient’s endpoint, and the 
proportion of patients who maintain 50% 
response criteria for 6 consecutive months 
during the 6-month, double-blind treatment

To compare galcanezumab with placebo with 
respect to changes in other efficacy parameters,
specifically:
o
ICHD migraine headache days
o
migraine attacks
o
migraine headache hours
o
headache hours
o
severity of remaining migraines

Overall mean change from baseline (during the 
6-month, double-blind treatment phase) on the 
following monthly measures:
o
ICHD migraine headache days
o
migraine attacks
o
migraine headache hours
o
headache hours
o
severity of remaining migraines

To compare galcanezumab with placebo with 
respect to global assessment of illness

Overall mean PGI-I rating during the 6-month,
double-blind treatment phase

To compare galcanezumab with placebo with 
respect to changes in disability and quality of 
life

Mean change from baseline on the following 
measures:
o
MIDAS total score and individual 
items at Month 6
o
MSQ v2.1 total score, and Role 

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 1 9
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
F u ncti o n -Pr e ve nti ve a n d E m oti o nal 
F u ncti o n d o mai n sc ores (a vera ge of 
M o nt hs 4, 5, a n d 6)
o
H C R U a n d em pl o y me nt stat us

T o e val uate patie nt satisfacti o n wit h me dicati o n

Satisfacti o n wit h me dicati o n usi n g t he
P S M Q -M.

T o c o m pare galca nez u ma b wit h place b o wit h
res pect t o safet y a n d t olera bilit y

A nal y sis of:
o
T E A Es
o
disc o nti n uati o n rates
o
vital si g ns a n d wei g ht
o
E C Gs
o
la b orat or y meas ures
o
ot her safet y para meters , incl u di n g
s uici dalit y usi n g t he C-S S R S

T o e val uate i m m u n o ge nicit y of galca nez u ma b

T hr o u g h o ut t he st u d y:
o
D e vel o p me nt a n d c o nse q ue nces of
a nti -dr u g a nti b o dies a n d ne utralizi n g
a nti -dr u g a nti b o dies t o galca nez u ma b

T o e val uate P K of galca nez u ma b

Ser u m c o nce ntrati o ns of galca nez u ma b

T o e val uate P D (tar get e n ga ge me nt) of
galca nez u ma b

Plas ma c o nce ntrati o ns of C G R P

T o assess c ha n ges i n efficac y o utc o mes d uri n g
St u d y Peri o d I V as c ollecte d b y e P R O diar y
data

T o c o m pare galca nez u ma b wit h place b o wit h
res pect t o c ha n ge i n use of ac ute (a b orti ve)
mi grai ne treat me nt ( M H D o nl y)

I n St u d y Peri o d I V:
o
Mea n c ha n ge fr o m baseli ne i n
m o nt hl y mi grai ne hea dac he da ys
o
Ti me t o first l oss of res p o nse a m o n g
patie nts w h o met t he 5 0 % res p o nse
rate criteria at t he e n d of t he d o u ble-
bli n d treat me nt p hase
o
Ti me t o i nitiati o n of treat me nt wit h a
mi grai ne pre ve nti o n me dicati o n

T he o verall mea n c ha n ge fr o m baseli ne i n t he
n u m ber of m o nt hl y mi grai ne hea dac he da ys
re q uiri n g me dicati o n f or t he ac ute treat me nt of
mi grai ne  hea dac he da y s d uri n g t he 6 -m o nt h
d o u ble bli n d treat me nt p hase
E x pl or at or y

T o e x pl ore P K /P D a n d e x p os ure-res p o nse
relati ons hi ps

A nal y sis of t he relati o ns hi p bet wee n baseli ne
plas ma C G R P c o nce ntrati o ns a n d efficac y
meas ures

A nal y sis of t he relati o ns hi p of ser u m
galca nez u ma b c o nce ntrati o ns t o plas ma C G R P
c o nce ntrati o ns, efficac y e n d p oi nts , a n d/ or
safet y e n d p oi nts.

T o c o m pare galca nez u ma b wit h place b o wit h
res pect t o cate g orical c ha n ges i n q ualit y of life

Perce nta ges of patie nts wit h:
o
≥5 0 % i m pr o ve me nt i n MI D A S t otal
C CI

I5Q-JE-CGAN(a) Clinical Protocol
Page 20
LY2951742 (galcanezumab)
score
o
change from baseline in MSQ Role 
Function-Restrictive domain ≥10.9 
o
change from baseline in MSQ Role 
Function-Preventive domain ≥8.3 
o
change from baseline in MSQ 
Emotional Function domain ≥12.2

To compare galcanezumab with placebo with 
respect to the proportion of migraine headache 
days or headache days requiring medication for 
the acute treatment of migraine headache or 
headache

To compare galcanezumab with placebo with 
respect to the proportion of migraine headache 
days requiring medication for the acute 
treatment of migraine headache

Change from baseline in the proportion of 
monthly migraine headache days or headache 
days requiring medication for the acute 
treatment of migraine headache or headache

Change from baseline in the proportion of 
monthly migraine headache days requiring 
medication for the acute treatment of migraine 
headache

To compare galcanezumab with placebo with 
respect to changes in symptomatology 
associated with migraine or probable migraine

Change from baseline in the number of monthly 
migraine headache days with:
o
nausea and/or vomiting
o
photophobia and phonophobia
o
aura
o
prodromal symptoms other than aura

To explore safety results during Study Period 
IV

Analysis of the following during Study Period 
IV:
o
FEAEs
o
discontinuation rates
o
vital signs and weight
o
ECGs
o
laboratory measures
o
other safety parameters , including 
suicidality using the C-SSRS and 
follow-up of emergent adverse allergic 
reactions or hypersensitivity
Abbreviations:  CGRP = calcitonin gene-related peptide; C-SSRS = Columbia–Suicide Severity Rating Scale;
FEAE = follow-up-emergent adverse event; ECG(s) = electrocardiogram(s); ePRO = electronic patient-reported 
outcomes; HCRU = healthcare resource utilization; ICHD = International Classification of Headache Disorders; 
MHD = migraine headache day; MIDAS = Migraine Disability Assessment test; MSQ v2.1 = Migraine-Specific 
Quality of Life Questionnaire version 2.1; PGI-I = Patient Global Impression-Improvement; 
PD = pharmacodynamic(s); PGI-S = Patient Global Impression of Severity; PK = pharmacokinetic(s); 
PSMQ-M = Patient Satisfaction with Medication Questionnaire-Modified; TEAE = treatment-emergent adverse 
event.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
Table CGAN.4.2.
Migraine and Headache Endpoint Definitions
Diagnosis
Definition/Criteria
Migraine headache
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 1 of the following:

Nausea and/or vomiting

Photophobia and phonophobia
(Definition adapted from the IHS ICHD-3 beta)
Probable migraine headache
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; 
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.
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.
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:  ICHD = International Classification of Headache Disorders; IHS = International Headache Society.

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LY2951742 (galcanezumab)
5.
Study Design
5.1.
Overall Design
Study CGAN is a multisite, randomized, double-blind, placebo-controlled bridging study of 
galcanezumab in Japanese outpatients suffering from migraine.  The study has 4 periods, 
including a prospective baseline phase to determine patient eligibility. Patients who complete 
Study Period III may have an option to roll-over to the open-label extension study, I5Q-JE-
CGAP (CGAP). Figure CGAN.5.1 illustrates the study design.
Figure CGAN.5.1.
Illustration of study design for Study I5Q-JE-CGAN.
Study Period I: The study and potential risks for both study I5Q-JE-CGAN and I5Q-JE-CGAP 
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 migraine-prevention treatments 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 
(Section 2).  Visit 1 will be complete when the last scheduled procedure of the screening 
assessment is completed.

I5Q-JE-CGAN(a) Clinical Protocol
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LY2951742 (galcanezumab)
Study Period II: 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 the treatment period.  Beginning at Visit 2, patients will log in daily to the 
electronic patient-reported outcomes (ePRO) system to answer questions about the occurrence of 
headaches, headache duration, headache features, severity of headache, and use of headache 
medication.  At the end of the prospective baseline period, sites will be notified whether their 
patients met the criteria and are eligible to be randomized to treatment at Visit 3.
To avoid biased reporting, patients must not be told the number of migraine headache days
on which study qualification is based.
Study Period III:  At the start of the 6-month, double-blind treatment phase (Visit 3), patients 
meeting all eligibility requirements will be randomized to 1 of 3 treatment groups in a 2:1:1 ratio 
to receive placebo, 120 mg/month galcanezumab, or 240 mg/month galcanezumab, respectively.
Patients randomized to the 120 mg dose of galcanezumab will receive an initial loading dose of 
240 mg (2 injections of 120 mg each at Visit 3 only).  To preserve blinding throughout the study, 
patients in all treatment groups will receive 2 injections of investigational product at each dosing 
visit.  At Visit 3, if available and where local regulations in Japan and ethical review 
boards/institutional review boards (ERBs/IRBs) allow, patients will also watch a training video 
designed to address patient expectations with regard to participation in a placebo-controlled trial,
and the difference between medical treatment and research.
The patient will be considered enrolled in the study when randomization occurs.  During this 
phase, study procedures at dosing visits must always occur prior to the patient receiving his/her
assigned treatment of study drug.
Patients will be given injections of study drug during office visits (Figure CGAN.5.1).  For all 
treatment groups, subcutaneous injections will be administered once monthly at the dosing visits.  
At Visit 3 (first dose), patients will be required to 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.  Patients 
will continue to log in and complete the ePRO diary each day.  Patients may continue to take 
their allowed acute migraine headache medication (with some limitations; see concomitant 
medication study tool) during the treatment phase.
Patients who do not participate in the CGAP study and who complete Study Period III, or who 
discontinue for any reason during Study Period III, will be expected to enter post-treatment 
follow-up (Study Period IV).
Patients who discontinue for any reason during Study Period III will be expected to take the 
measurement for Early Termination (ET).
Study Period IV: Only patients who do not participate in the CGAP study will move on to 
Study Period IV. During this 4-month phase, sites and patients will remain blinded to patients’ 
treatment assignments.  Patients will follow all study procedures during Study Period IV, but will 

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not receive galcanezumab or placebo.  One month after Visit 12, if clinically warranted due to a 
worsening of symptoms, patients may start migraine prevention medications at the discretion of 
the investigator.  The list of allowed preventive medications is provided in the concomitant 
medication study tool.  At Visit 14 (Month 10), patients will return to the site for their last study 
visit and discharge from the study.  
Patients who discontinue for any reason during Study Period IV will be expected to take the 
measurement for ET.
5.2.
Number of Participants
Approximately 902 participants will be screened to achieve 451 randomized participants for an 
estimated total of 225 evaluable participants in the placebo group and 113 evaluable participants 
each in the galcanezumab (120 mg and 240 mg) treatment groups.
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 randomized treatment phase is considered sufficient to assess the safety and 
efficacy of a migraine prevention medication, and is consistent with Studies CGAH/CGAG. 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.  For the roll-over patients, a 5-
month, post-treatment observation period will be conducted after treatment for an additional 12 
months in Study CGAP.
5.5.
Justification for Dose
This study is a bridging study with 2 global Phase 3 studies (I5Q-MC-CGAG [CGAG] and I5Q-
MC-CGAH [CGAH]). Therefore, the doses selected for this study were the same doses used in 
Studies CGAG and CGAH. In Studies CGAG and CGAH, doses of 120 mg and 240 mg 
galcanezumab administered once monthly were selected primarily on the basis of clinical 
efficacy and PK/PD data from the Phase 2 dose-ranging study, I5Q-MC-CGAB (CGAB). 
Results from Study CGAB indicated that 120 mg was statistically significantly superior to 
placebo at the last 28-day period of the 3-month treatment phase in mean change in migraine 
headache days, as well as in other measures of efficacy and quality of life.  The use of a loading 
dose for the 120-mg treatment arm, and the inclusion of a 240-mg treatment arm, is based on the 
finding that a dose higher than 120 mg achieved statistically significant separation from placebo 
as early as Month 1. 

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In the Phase 1 study (Study I5Q-MC-CGAE [CGAE]), single doses of galcanezumab up to 
300 mg and three every-4-week (Q4W) 300-mg doses of galcanezumab were well tolerated in 
both Japanese and Caucasian subjects.

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6.
Study Population
All patients 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, 
neurological examination, clinical laboratory tests, ECGs, and migraine history during screening 
and a prospective baseline period, as described in the Inclusion (Section 6.1) and Exclusion 
(Section 6.2) Criteria.  The nature of any comorbid conditions present at the time of the physical 
examination and any preexisting 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 rescreening once, with approval from Eli Lilly and Company (Lilly) Medical 
(Section 6.4).  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 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 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.  To 
avoid biased reporting, patients must not be told the number of migraine 
headache days on which study qualification is based.
[5]
From Visit 2 to Visit 3 (prospective baseline period), must achieve sufficient 
compliance with ePRO daily headache entries, as demonstrated by completion 
of at least 80% of daily diary entries.
Informed Consent and Patient Agreements
[6]
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.
[7]
Are reliable and willing to follow study procedures, including all follow-up 
visits.

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[8]
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
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.
[9]
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 [8],
or for male patients who meet the criterion defined in definition 3) of 
inclusion criterion [8].
[10] 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
[11] 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.  
[12] 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.

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[13] 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.
Prior/Concomitant Therapy
[14] Patients who are taking, or are expected to take, therapeutic antibodies
(including chimeric antibodies) during the course of the study (for example, 
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.
[15] Known hypersensitivity to multiple drugs, monoclonal antibodies or other 
therapeutic proteins, or to galcanezumab and the excipients in the 
investigational product.
[16] 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.
[17] 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.
Diagnostics Assessments
[18] 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.
[19] History of headache (for example, cluster headache, medication overuse 
headache) other than migraine or tension-type headache, as defined by IHS 
ICHD-3 beta within 3 months prior to randomization.  
[20] Prior to Visit 1, a history of ≥15 headache days (migraine, probable migraine,
or any other headache) per month, on average, during the past 3 months, or 
are suspected of suffering from chronic migraine, as defined, per ICHD-3 
beta.
[21] History of head or neck injury within 6 months prior to Visit 1.
[22] History of traumatic head injury associated with significant change in the 
quality or frequency of headaches.

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Medical Conditions
[23] Have ECGs showing abnormalities compatible with acute cardiovascular 
events and/or serious cardiovascular risk, including, but not limited to, a 
Fridericia’s corrected QT (QTcF) interval >470 msec for women and 
>450 msec for men, or have had myocardial infarction, unstable angina, 
percutaneous coronary intervention, coronary artery bypass graft, stroke, or 
deep vein thrombosis/pulmonary embolism within 6 months of screening, or 
have planned cardiovascular surgery or percutaneous coronary angioplasty.
[24] Patients with a body mass index (BMI) ≥40 kg/m2 at Visit 1.
[25] 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 (TBL) >1.5X ULN, or alkaline phosphatase (ALP) 
>2X ULN must be discussed and judged not clinically significant by Lilly 
Medical prior to enrollment.
[26] 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 is 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.
[27] 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 who 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 with the ideation or behavior occurring within the past month.
[28] Women who are pregnant or nursing.
[29] Patients who have used opioids or barbiturate containing analgesic more than 
twice 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).
[30] Patients with a history of drug or alcohol abuse/dependence within 1 year 
prior to Visit 1 (excessive or compulsive use as judged by the investigator), or 
who are 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.

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[31] 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.
[32] 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.
Other Exclusions
[33] Have other issues that, in the opinion of the investigator, would interfere with 
compliance with the study requirements and completion of evaluations 
required for this study.
[34] 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.
[35] Are Lilly employees.
[36] Are unwilling or unable to comply with the use of data collection devices.
6.3.
Lifestyle Restrictions
No changes in lifestyle or dietary requirements are required during the study. 
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be
considered for rescreen 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 [8]

Exclusion criterion [12]

Exclusion criterion [14]

Exclusion criterion [16]

Exclusion criterion [28]
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.

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In addition, after consultation with and approval by a Lilly Medical representative, a patient may 
be rescreened if there is an unexpected technical difficulty with the electronic diary capture 
during the prospective baseline period.

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7. Treatments
7.1.
Treatments Administered
This study involves a comparison of galcanezumab (120 and 240 mg) administered once 
monthly with placebo.  Sites will administer subcutaneous injections of the study drug
(galcanezumab and/or placebo) at 6 visits during the treatment phase (Section 2).
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: 

Explaining the correct use of the investigational agent(s) to the patients, site 
personnel, and/or legal representatives.

Verifying that instructions are followed properly.

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.
7.1.1. Packaging and Labeling
Galcanezumab and matching placebo (excipients only) will be supplied as an injectable solution 
in 1-mL, single-dose, prefilled, disposable, manual syringes with study-specific labels.  Each 
syringe of galcanezumab is designed to deliver galcanezumab 120 mg.  The syringes (and 
contents), containing either 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 Japanese 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
Patients who meet all criteria for enrollment will be randomized to double-blind treatment at 
Visit 3. Assignment to treatment groups will be determined by a computer-generated random 
sequence using an interactive web-response system (IWRS).  The IWRS will be used to assign 
double-blind investigational product to each patient. Site personnel will confirm that they have 
located the correctly assigned package by entering the confirmation number found on the 
package into the IWRS prior to administration. 
To achieve between-group comparability, the randomization will be stratified by baseline 
migraine frequency (<8 migraine headache days versus ≥8 migraine headache days). To ensure 

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an appropriate balance of low- and high-frequency migraine headache-day patients, the sponsor
will stop enrollment of low-frequency patients, if the number exceeds an estimated 315.
Note that the treatment arm of the long-term extension study CGAP, which is rolled over from 
Study CGAN, will be determined at CGAN Visit 3 (at the timing of CGAN randomization).  The 
detail of method of treatment assignment is described in the protocol 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 a double-blind study. To preserve blinding throughout the study, patients in all treatment 
groups will receive 2 injections of investigational product at each dosing visit.
To preserve the blinding of the study, a minimum number of Lilly personnel will see the 
randomization table and treatment assignments before the study is complete.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  All 
unblinding events are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient 
remain in the study, the investigator must obtain specific approval from a Lilly clinical research 
physician (CRP) or clinical research scientist (CRS) for the patient to continue in the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted.  Patient safety must always be the first 
consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the Lilly CRP/CRS prior to 
unblinding a patient’s treatment assignment, unless this could delay emergency treatment of the 
patient.  If a patient’s treatment assignment is unblinded, Lilly must be notified immediately.
7.4.
Dosage Modification
Dose modifications are not permitted in this study.
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 
refrigerator 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.

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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. Study Extensions
Patients who complete this study through Visit 12 (6 months) may be eligible to participate in 
Study I5Q-JE-CGAP (CGAP), if enrollment criteria for Study CGAP are met.  Approximately
240 patients will be rolled over to the open-label study CGAP, which has 2 arms:  galcanezumab
120 mg and galcanezumab 240 mg.  Patients who enroll in the CGAP study will roll over 
directly at the end of the CGAN double-blind treatment period (Study Period III), skipping the 4-
month, follow-up period (Study Period IV).
7.8.2. Continued Access
Following a patient’s completion of Study CGAN, he/she will not have continued access to
investigational product. Patients who enroll in Study CGAP will continue to receive
galcanezumab as part of Study CGAP.

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8.
Discontinuation Criteria
Patients who discontinue the study or investigational product during the double-blind treatment
phase (Study Period III) will proceed immediately to the post-treatment follow-up period (Study 
Period IV).
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 CRP 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 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 the study indication (prevention 
of migraine) during Study Period III, discontinuation from the study occurs 
prior to introduction of the new agent.
o
If, in the opinion of the investigator, a clinically significant event (CSE) 
occurs that warrants discontinuation of the study drug.  A CSE will be defined 
as a moderate-to-severe AE, abnormal clinical sign, or clinical laboratory 
finding that may pose a serious risk to the well-being of the patient.

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 good clinical practice.
Patients who discontinue the study early (Study Period 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 (Study Period 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 who 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 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.
Efficacy Assessments
An ePRO system and eCRF will be used to collect primary and secondary efficacy assessments.
Patient migraine headache data will be entered by the patients into an ePRO diary, and patient-
rated scales/questionnaires will be collected directly via an ePRO tablet at each visit. The use of 
these ePRO devices and of the electronic clinical outcome assessment (eCOA) system is 
described in the Data Capture System section of Appendix 3 (Appendix 3.2.1).
9.1.1. Primary Efficacy Assessments
The primary efficacy endpoint is the overall mean change from baseline in the number of 
monthly migraine headache days during the 6-month, double-blind treatment phase (average of 
Months 1-6).  Migraine headache day will be defined in Table CGAN.4.2. Patients will be asked 
to use an ePRO device (starting at Visit 2) to record headache symptoms, duration, and severity.   
9.1.2. Secondary Efficacy Assessments
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 efficacy and safety 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 or not 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.  The investigator answers yes/no when making this 
assessment.
Planned surgeries and nonsurgical interventions should not be reported as AEs, unless the 
underlying medical condition has worsened during the course of the study.
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 (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

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
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.
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.  
United States 21 CFR 312.32 and European Union 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. 
Nonserious AEs obtained through the questionnaire are recorded and analyzed separately.  Only 
SAEs 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 

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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.
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
9.4.1. 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, except for screening,
and should be recorded according to the study-specific recommendations included in the ECG 
manual.
Any clinically significant finding from ECGs that results in a diagnosis should be reported to 
Lilly or its designee as an AE via eCRF.
9.4.2. 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 Schedule of Activities [Section 2]). Weight will be measured at screening 
and at Visits 12 and 14 or at ET (see Schedule of Activities [Section 2]).
Any clinically significant finding from vital signs measurement that results 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 finding from laboratory tests that results in a diagnosis should be 
reported to Lilly or its designee as an AE via eCRF.
In addition, an immunogenicity and PK serum sample will be collected, when possible, for any 
patient who experiences a potential systemic allergic/hypersensitivity reaction during the study,

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as judged by the investigator. This immunogenicity and PK serum sample should be collected 
immediately or as soon as possible, taking into consideration the availability and well-being of 
the patient. In this case, serum concentrations of galcanezumab will be determined for 
immunogenicity evaluation. 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 to 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.  Galcanezumab concentration information that may/would unblind the study 
will not be reported to investigative sites or blinded personnel until the study has been unblinded.
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.  It is intended that blood samples collected 
from patients who received placebo should not be analyzed for determination of serum 
concentrations of galcanezumab.
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 

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 4 2
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
last-d ose a d mi nistrati o n , pri or t o bl o o d sa m pli n g , s h o uld be rec or de d .  T he act ual date a n d ti me
( 2 4-h o ur cl oc k t i me) of eac h sa m pli n g will be rec or de d
A vali date d galca nez u ma b -t olera nt assa y will be use d t o deter mi ne plas ma C G R P 
c o nce ntrati o ns.  Sa m ples will be a nal yze d at a la b orat or y a p pr o ve d b y t he s p o ns or.
Pl as ma C G R P c o nce ntrati o n i nf or mat i on t hat m a y/ w o uld u n b li n d t he st u d y will not be re p orte d 
t o i n vesti gati ve sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
Bi oa nal y tic al sa m ples c ollecte d t o meas ure C G R P will be i de nt ifie d b y t he patie nt n u m ber 
(c o de d) a n d retai ne d f or a ma xi m u m of 1 year f oll o wi n g last patie nt visit f or t he st u d y at a 
facility selecte d b y t he s p o ns or . 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
9. 8.
Bi o m ar k er s
Pl as ma a n d w h ole bl oo d R N A a n d e pi ge net ic sa m ples f or bi o mar ker researc h will  be c ollecte d at 
t he ti mes s pecifie d i n t he Sc he d ule o f Act i vities ( Secti o n 2 ), w here l ocal re g ulat i ons a n d E R Bs
all o w.
C CI

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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, 
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 the galcanezumab as specified in the 
Schedule of Activities (Section 2). Immunogenicity will be assessed by a validated assay 
designed to detect anti-drug antibodies in the presence of the investigational product.  Antibodies 
may be further characterized and/or evaluated for their ability to neutralize the activity of the 
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 
the 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 healthcare 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 et al. 1999; Stewart et al. 
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-

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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 
(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 their 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.
Patient 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
The study will enroll approximately 451 patients.  Eligible patients will be randomized in 
blinded fashion in a 2:1:1 ratio to placebo (target of 225 patients), galcanezumab 120 mg/month 
(target of 113 patients), or 240 mg/month (target of 113 patients).  With the assumption of a 15% 
discontinuation rate and an effect size of 0.36, it is estimated that this sample size will provide 
approximately 88% power that at least 1 dose of galcanezumab will separate from placebo at a 
two-sided significance level of 0.05 based on simulations using the Dunnett test (Dunnett 1955).  
Assumptions in the simulations were based on the assumptions for global Phase 3 studies, with 
adjustment to reflect less dropout and less variability in a more homogenous Japanese study.
Approximately 902 patients may be screened to ensure randomization of 451 patients, with an 
estimated 383 patients completing the study.
10.2. Populations for Analyses
Populations are defined, for the purpose of analysis, in Table CGAN.10.1.
Table CGAN.10.1.
Populations for Analyses
Population
Description
All Randomized Patients (ARP)
All patients who are randomized at Visit 3. 
Intent-to-Treat (ITT) Population
All patients who are randomized at Visit 3 and received at least one dose of 
study drug. Patients in the ITT population will be analyzed according to the 
treatment that they were randomized to.  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 post-treatment phase (Study Period IV) as indicated 
by entering any post-treatment visit.  
Per Protocol Set (PPS)
ITT population who has no important protocol deviation which impact efficacy 
analysis. Details will be specified in SAP.
Abbreviations:  SAP = statistical analysis plan.
10.3. Statistical Analysis
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, analyses will be conducted on an intent-to-treat (ITT) population, 
which will include all patients who are randomized at Visit 3 and receive at least 1 dose of study 
drug.  Patients in the ITT population will be analyzed according to the treatment group to which 
they are randomized.  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.

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Unless otherwise specified, hypothesis tests will be based on two-sided alpha level of 0.05. For 
the primary analysis and the other continuous efficacy analyses, multiplicity adjustment (120 mg 
versus placebo and 240 mg versus placebo), such as Dunnett’s procedure, will be used if 
appropriate.  Details will be specified in SAP.
The primary analysis will be performed using a restricted maximum likelihood-based mixed 
models repeated measures (MMRM) technique using the Step-down version of Dunnett’s 
procedure (Section 10.3.3.1). The analysis is based on the double-blind period (Study Period III) 
only.
In addition to the MMRM approach, sensitivity analysis of covariance (ANCOVA) model using 
the last observation carried forward (LOCF) to account for missing data will be conducted to 
provide additional information for the primary and continuous secondary measures, as well as 
continuous health outcome measures.
Visit-wise binary efficacy variables will be analyzed using a generalized linear mixed model 
(GLIMMIX) as pseudo-likelihood-based mixed effects repeated measures analysis (MMRM-
CAT).
Categorical safety measures (including percentages of patients with TEAEs, SAEs, and AEs 
reported as a reason for discontinuation, as well as those patients who met categorical criteria for 
changes in vital signs and weight, ECGs, and laboratory tests) will be analyzed using Fisher’s 
exact test.  
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 all treatment groups for Study Period III (double-blind treatment) and 
Study Period IV (post-treatment follow-up) both overall and by visit. In addition, the number and 
percentage ITT patients who roll over to CGAP will summarized for all treatment groups.
Patient allocation by investigator will be summarized for Study Period III and Study Period IV 
for all ITT patients.  Patient allocation by investigator will also be listed for all study periods.
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, body mass index [BMI]) 

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
Migraine headache, headache, variation of migraine/headache measures per 30-day 
baseline period. 

Alcohol, tobacco, caffeine, and nicotine consumption 

Medical history and preexisting conditions

Other baseline variables used for subgroup analysis (eg, baseline anti-drug antibodies 
[see Section 10.3.6.2])
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 ePRO) will be summarized for all ITT patients for 
Study Period III and Study Period IV, separately.
10.3.2.4. Treatment Compliance
Not applicable. 
10.3.2.5. Electronic Patient-Reported Outcome Diary Compliance
ePRO diary compliance at each period (including baseline, Month 1, 2, 3, … until Month 10) 
will be calculated.  Diary compliance at each period is calculated as: 
Actual number of diary days is calculated as the total number of days with non-missing answers.
10.3.3. Primary and Secondary Analyses
10.3.3.1. Primary Analyses
The primary efficacy objective is to assess whether at least 1 dose of galcanezumab (120 or
240 mg/month) is superior to placebo in the prevention of migraine headache in patients with
episodic migraine.
The primary efficacy measure is the overall mean change from the baseline period in the number 
of monthly migraine headache days during the 6-month, double-blind treatment phase (average 
of Months 1-6; Study Period III), and the primary analysis will evaluate the efficacy of 
galcanezumab (120 or 240 mg/month) compared with placebo. The analysis is based on ITT 
population. It will be performed using a restricted maximum likelihood-based MMRM 
technique.  The analysis will include the fixed categorical effects of treatment, month, and 
treatment-by-month interaction, as well as the continuous fixed covariates of baseline number of 
migraine headache days and baseline number of migraine headache days-by-month interaction.
The primary endpoint of this study for each galcanezumab dose arm compared with placebo will 
be estimated as the main effect of treatment from the MMRM analysis during the 6-month 

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treatment phase. This provides the average treatment effect across 6 months of double-blind 
treatment phase. The repeated-measures analysis will include data from all 3 treatment groups.
For the multiplicity adjusted p-value calculation, the pairwise treatment effect comparisons of 
each dose of galcanezumab versus placebo will be conducted using the step-down version of 
Dunnett’s procedure at the two-sided alpha level of 0.05.  
For sensitivity analysis purpose, ANCOVA will be used on ITT population.
For sensitivity analysis purpose, MMRM will be used on PPS population.
10.3.3.2. Key Secondary Analyses
The key secondary measures will be analyzed for the double-blind treatment (Study Period III).
For the continuous key secondary measures, the change from baseline during the 6-month,
double-blind treatment phase will be analyzed by repeated measures analyses similar to the one 
described in Section 10.3.3.1. For the analysis of 50%, 75%, and 100% response, the percentage 
of patients meeting response criteria during the 6-month double-blind treatment phase will be 
estimated by MMRM-CAT using the GLIMMIX procedure in SAS®.
10.3.3.3. Other Secondary and Exploratory Efficacy Analyses
The other secondary and exploratory efficacy analyses will be conducted for the double-blind 
treatment phase, and for the double-blind treatment and post-treatment follow-up phases (Study 
Period III and Study Period IV) combined. Further details regarding other secondary and 
exploratory efficacy analyses are summarized in the SAP.
10.3.4. Safety Analyses
The safety analyses will be conducted for the double-blind treatment and post-treatment follow-
up phases, as well as the 2 periods combined.  For the 2 phases combined, only repeated 
measures and time-to-event analyses will be conducted.
The safety and tolerability of treatment will be assessed by summarizing the following:

adverse events
o
TEAEs

by preferred term

by SOC

by maximum severity

by outcome

considered to be related to investigational product by investigator
o
SAEs
o
AEs leading to discontinuation
o
follow-up-emergent adverse events (FEAEs) during Study Period IV.

Suicidal ideation and behaviors assessed by solicited questioning using the C-SSRS

Vital signs and weight

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
ECGs

Laboratory measurements

Anti-galcanezumab antibody measurements
10.3.4.1. Categorical Safety Variables
Unless specified otherwise, the categorical safety analyses will include both scheduled and 
unscheduled visits.
Comparisons between treatment groups for all categorical safety measures will be made using 
the Fisher’s exact test for Study Period III (double-blind treatment) with the ITT population.  
Descriptive statistics only will be presented for the treatment groups in the post-treatment 
follow-up phase (Study Period IV) with the post-treatment population.
10.3.4.2. Adverse Events
Treatment-emergent adverse events are defined as the reported AEs that first occurred or 
worsened during the postbaseline phase compared with baseline phase.  For each TEAE, the 
severity level of the event (mild, moderate, or severe) will be determined by patient or physician 
opinion.  The Medical Dictionary for Regulatory Activities (MedDRA) Lowest Level Term will 
be used in the treatment-emergent computation.  For each Lowest Level Term, the maximum 
severity at baseline will be used as the baseline severity.  If the maximum severity during 
postbaseline is greater than the maximum baseline severity, the event is considered to be 
treatment-emergent for the specific postbaseline period.  For each patient and TEAE, the 
maximum severity for the MedDRA level being displayed (Preferred Term, High Level Term, or 
SOC) is the maximum postbaseline severity observed from all associated Lowest Level Terms 
mapping to that MedDRA level.
For events that are gender-specific, the denominator and computation of the percentage will 
include only patients from the given gender.
Similar to TEAEs, FEAEs will be analyzed. 
10.3.4.3. Suicide-Related Thoughts and Behaviors
Suicide-related events occurring during the study, based on the C-SSRS, will be summarized by 
treatment. In particular, for each of the following suicide-related events, the number and percent 
of patients with the event will be enumerated by treatment: completed suicide, nonfatal suicide 
attempt, interrupted attempt, aborted attempt, preparatory acts or behavior, active suicidal 
ideation with specific plan and intent, active suicidal ideation with some intent to act without 
specific plan, active suicidal ideation with any methods (no plan) without intent to act, non-
specific active suicidal thoughts, and wish to be dead. The number and percent of patients with 
self-injurious behavior with no suicidal intent occurring during treatment will also be enumerated 
by treatment.
In addition, the number and percent of patients who experienced at least 1 of the various 
composite measures will be presented. These include suicidal behavior (completed suicide, non-
fatal suicidal attempts, interrupted attempts, aborted attempts, and preparatory acts or behavior), 

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suicidal ideation (active suicidal ideation with specific plan and intent, active suicidal ideation 
with some intent to act without specific plan, active suicidal ideation with any methods [no plan] 
without intent to act, non-specific active suicidal thoughts, and wish to be dead), and treatment-
emergent suicidal ideation.
The Fisher’s exact test will be used for treatment comparisons.
10.3.4.4. Vital Signs and Weight
Vital signs collected during the study include systolic and diastolic blood pressure, pulse, and 
temperature. Blood pressure and pulse measurements will be taken when the patient is in a 
sitting position. Three measurements of sitting blood pressure and pulse will be collected at 
every visit; the 3 sitting blood pressure and pulse measurements will be averaged and used as the 
value for that visit for analysis.
The incidence rates of patients with treatment-emergent vital sign and weight changes based at 
any time postbaseline and at LOCF endpoint will be assessed using the Fisher’s exact test.  
Specific criteria for treatment emergent definition will be documented in the SAP.
10.3.4.5. Electrocardiogram Intervals and Heart Rate
Analyses of corrected QT interval will be calculated using 2 correction formulas. The QTcF 
(measured in milliseconds [msec]) will be calculated with Fridericia’s formula as QT/RR⅓.  The 
Large Clinical Trial Population Based QT Correction (QTcLCTPB) (msec) will be calculated 
with the formula as QT/RR0.413. The number and percent of patients meeting criteria for 
treatment-emergent abnormalities in ECG intervals (pulse rate, QRS, QTcF, and QTcLCTPB) 
and heart rate at any time during study will be summarized.  Treatment group comparisons will 
be performed using the Fisher’s exact test.
10.3.4.6. Laboratory Tests
The incidence rates of patients with treatment-emergent abnormal, high, or low laboratory values 
at any time postbaseline and at LOCF endpoint will be assessed using the Fisher’s exact test for 
each laboratory test.
Patients will be defined as having a treatment-emergent low value if they have all normal or high 
values at baseline, followed by a value below the lower reference limit at any postbaseline visit. 
Patients with all normal or high values at baseline (no low values) will be included in the 
analysis of treatment-emergent low laboratory values. Patients will be defined as having a 
treatment-emergent high value if they have all normal or low values at baseline, followed by a 
value above the upper reference limit at any postbaseline visit.  Patients with all normal or low 
values at baseline (no high values) will be included in the analysis of treatment-emergent high 
laboratory values.
For analytes simply classified as normal or abnormal, patients will be defined as having a 
treatment-emergent abnormal value if they have all normal values at baseline, followed by an 
abnormal value at any postbaseline visit.  Patients with all normal values at baseline will be 
included in the analysis of treatment-emergent abnormal laboratory values.

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 5 1
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
 
 
 
 
 
1 0. 3. 6. Ot h er A n al y s e s
1 0. 3. 6. 1. M e di c al R e s o ur c e Utili z ati o n a n d H e alt h E c o n o mi c s
T he c ha n ge fr o m baseli ne t o eac h p ost baseli ne visit f or t he d o u ble -bli n d treat m e nt p hase a n d f or 
t he d o u ble-bli n d tre at me nt  a n d p ost-treat me nt fol l ow- u p p hases c o m bi ne d f or M S Q v 2. 1 ( R ole 
F u nct i on- Restri ct i ve, R ole F u ncti on- Pre ve nt i ve, E m oti onal F u nct i on, a n d t otal  sc ore) a n d 
MI D A S (ite m sc ores a n d t otal sc ore) will be a nal yze d. 
I n a d diti on, cate g orical a nal ysis f or t he
fre q ue nc y meas ure will be perf or me d.
T he H C R U a n d P S M Q - M will be a nal yze d wit h details d oc u me nte d i n t he S A P.
1 0. 3. 6. 2. S u b gr o u p A n al y s e s
S u b gr o u p a nal yses (Ta ble C G A N. 1 0. 2 ) will be perf or me d f or t he pri mar y efficac y meas ure 
(c ha n ge fr om baseli ne i n t he n u m ber of mi grai ne hea dac he da ys) o nl y f or t he I T T patie nts i n 
St u d y  P erio d III.
C CI

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 5 2
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
T a bl e C G A N. 1 0 . 2.
D efi niti o n of S u b gr o u p V ari a bl e s
S u b gr o u p V ari a ble
C ate g ories
Se x
Male, fe male
Baseli ne n u m ber of mi grai ne hea dac he da ys
2 le vels of baseli ne mi grai ne fre q ue nc y :
< 8 mi grai ne hea dac he da ys
≥8 mi grai ne hea dac he da ys
Treat me nt -resista nt stat us
Treat me nt -resista nt stat us a b o ut w het her a patie nt has 
faile d 2 or m ore pr o p h ylactic treat me nts ( Yes or N o)
Ha vi n g a ura or n ot ( d uri n g baseli ne peri o d)
Yes or N o
Baseli ne a nti -dr u g a nti b o d y stat us
A n y  c o nfir me d p ositi ve a nti-dr u g a nti b o d y at baseli ne 
( Yes vs N o)
Ne utralizi n g a nti -dr u g a nti b o d y stat us
A n y  p ositi ve ne utralizi n g a nti-dr u g a nti b o d y ti me p oi nt 
( Yes vs N o) – n ote t hat ne utralizi n g a nti -dr u g a nti b o d y 
assa ys ar e perf or me d o nl y o n c o nfir me d -p ositi ve a nti -
dr u g a nt i b o dies
Treat me nt -e mer ge nt a nti -dr u g a nti b o d y stat us
A n y  treat me nt-e mer ge nt a nti -dr u g a nti b o d y ( Yes vs N o)
 
 
 
 
 
 
C CI

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 5 3
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
 
 
 
 
1 0. 3. 7. I nt eri m A n al y s e s
A data m o nit ori n g c o m mittee ( D M C) is n ot pla n ne d f or t his st u d y .
A n i nteri m a nal ysis ma y be c o n d ucte d after all ra n d o mize d pat ient s c o mplete t he d o u bl e- bli n d 
treat me nt perio d ( St u d y Perio d III) of  t he st u d y. T h us , it will be t he fi nal a nal ysis of t he pri mar y 
efficac y e nd p oi nt. It will be c o n d ucte d usi n g i nter nal, u n bli n de d st u d y tea m me m bers w h o d o 
n ot ha ve direct i nteracti o n wit h sites.
U n bli n di n g details are s pecifie d i n t he u n bli n di n g pla n sect i on of t he S A P or a se parate 
u n bli n di n g pla n d oc u me nt .
C CI

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11.
References
Buzzi MG, Bonamini M, Moskowitz MA. Neurogenic model of migraine. Cephalalgia.
1995;15(4):277-280. 
Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS. Safety and 
efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the 
prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet 
Neurol. 2014;13(9):885-892.
Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. 
J Am Stat Assoc. 1955;50(272):1096–1121.
Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S. Increase in plasma calcitonin 
gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster 
headache attack. Pain. 1995;60(2):119-123.
Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing
cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol.
1993;33(1):48-56.
Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation
of humans during migraine headache. Ann Neurol. 1990;28(2):183-187.
Guy W. ECDEU assessment manual for psychopharmacology, revised.. Rockville, MD: National 
Institute of Mental Health, Psychopharmacology Research Branch. 1976:217-222. Available 
at: https://archive.org/details/ecdeuassessmentm1933guyw. Accessed 27 July 2015.
[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.
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.
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.
Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, 
Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Effects of 
fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology. 2012;78(16):1207-
1214. 
Nagai K, Hayashi K, Yasui T, Katanoda K, Iso H, Kiyohara Y, Wakatsuki A, Kubota T, 
Mizunuma H. Disease history and risk of comorbidity in women's life course: a 
comprehensive analysis of the Japan Nurses’ Health Study baseline survey. BMJ Open.
2015;5(3):e006360.
Peroutka SJ. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and 
challenges in treating headache. BioDrugs. 2014;28(3):237-244.

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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].
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
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
ANCOVA
analysis of covariance
ARP
All Randomized Patients
AST
aspartate aminotransferase
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the [patient/subject] nor any of the 
investigator or sponsor staff who are involved in the treatment or clinical evaluation of 
the subjects are aware of the treatment received.
BMI
body mass index
BUN
blood urea nitrogen
CGRP
calcitonin gene-related peptide
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
COA
Clinical Outcome Assessment
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.
CPK
creatinine phosphokinase
CRP/CRS
Clinical Research Physician/Clinical Research Scientist: Individual responsible for the 
medical conduct of the study.  Responsibilities of the CRP may be performed by a 
physician, clinical research scientist, global safety physician or other medical officer.

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CSE
clinically significant event
C-SSRS
Columbia–Suicide Severity Rating Scale
CSR
clinical study report
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCOA
electronic clinical outcome assessment
eCRF
electronic case report form
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.
enter
Patients entered into a trial are those who sign the ICF directly or through their legally 
acceptable representatives.
EM
episodic migraine
ePRO
electronic patient-reported outcomes
ERB
Ethical Review Board
ET
early termination
FEAE
follow-up emergent adverse event: an event that first occurred or worsened during the 
follow-up period (Study Period IV) when compared to the double-blind treatment 
period (Study Period III)
FSH
follicle-stimulating hormone
GCP
good clinical practice
GGT
gamma glutamyltransferase
GLIMMIX
generalized linear mixed model
HbA1c
glycated hemoglobin
HCRU
healthcare resource utilization
HDL
high-density lipoprotein
IB
Investigator’s Brochure
ICF
informed consent form
ICHD
International Classification of Headache Disorders

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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.
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IgM
immunoglobulin M
INR
International Normalized Ratio
IRB
institutional review board
ITT
intention 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 (that is, 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
IWRS
interactive web-response system
LOCF
last observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
MHD
migraine headache day
MIDAS
Migraine Disability Assessment test
MSQ v2.1
Migraine Specific Quality of Life Questionnaire version 2.1
MMRM
mixed models repeated measures
MMRM-CAT
categorical mixed models repeated measures
PD
pharmacodynamics
PGI-I
Patient Global Impression of Improvement
PGI-S
Patient Global Impression of Severity
PK
pharmacokinetics

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PPS
Per-Protocol Set
PSMQ-M
Patient Satisfaction with Medication questionnaire-modified
Q4W
administration once every 4 weeks
QTc
corrected QT interval
QTcF
Fridericia’s corrected QT interval
QTcLCTPB
Large Clinical Trial Population Based QT Correction
RBC
red blood cell
RNA
ribonucleic acid
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. 
SHFU
Self-Harm Follow-Up form
SHSF
Self-Harm Supplement form
SOC
system organ class
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.
TPO
third-party organization
ULN
upper limit of normal
US
United States
WBC
white blood cell

I 5 Q-J E -C G A N ( a) Cli ni c al Pr ot o c ol
P a g e 6 1
L Y 2 9 5 1 7 4 2 (g al c a n e z u m a b )
A p p e n di x 2.
Cli ni c al L a b or at or y  T e st s
Cli nic al L a b or at or y Tests
He m at ol o g y
Cli nic al C he mistr y
He m o gl o bi n
Ser u m C o nce ntr ati o ns of:
He mat ocrit
S o di u m
Er y t hr oc yte c o u nt ( R B C)
P otassi u m
Mea n cell v ol u me
T otal bilir u bi n
Mea n cell he m o gl o bi n c o nce ntrati o n
Direct bilir u bi n
Le u k oc ytes ( W B C)
Al kali ne p h os p hatase
Ne utr o p hils, se g me nte d
Ala ni ne a mi n otra nsferase ( A L T)
L y m p h oc y t es
As partate a mi n otra nsferase ( A S T)
M o n oc ytes
Bl o o d urea nitr o ge n ( B U N)
E osi n o p hils
Creati ni ne
Bas o p hils
Ur ic aci d
Pl atelets
Calci u m
Gl uc ose
Al b u mi n
Uri n al ysis
Creati ne ki nase ( C K)
S pecific gra vit y
Tri gl yceri des
p H
T otal c h olester ol
Pr otei n
Hi g h -de nsit y li p o pr otei n ( H D L )
Gl uc ose
Ket o nes
Bl o o d
H b A 1c
Ur i ne le u k oc yte esterasea
Micr osc o pic a nal ysis
a
Ot her
Ur i ne c ult urea
P K sa m ple ( L Y 2 9 5 1 7 4 2 ser u m c o nce ntrati o n 
deter mi nati o n)
I m m u n o ge nicit y
Ur i ne Dr u g Scree n b
Pre g n a nc y Test (fe males o nl y)b
Ser u m pre g na nc y or F S H
Ur i ne pre g na nc y test ( perf or me d b y site)
St ore d S a m ples
Bi o mar ker st ora ge
R N A / E pi ge netic
A b bre viati o ns:  C G R P = calcit o ni n ge ne -relate d pe pti de; D N A = de o x yri b o n ucleic aci d; F S H = f ollicle -sti m ulati n g 
h or m o ne; H b A 1c = gl ycate d he m o gl o bi n ; P K = p har mac o ki netic; R B C = re d bl o o d cell; R N A = ri b o n ucleic aci d; 
W B C = w hite bl o o d cell .
a
A p ositi ve uri ne le u k oc yte esterase res ult will re q uire a f oll o w -u p sa m ple wit h micr osc o pic a nal ysis a n d p ossi bl y 
a uri ne c ult ure
b
Ma y  be re peate d d uri n g t he st u d y at t he discreti o n of t he i n vesti gat or.
C CI
C CI

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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/her participation in the trial.
Appendix 3.1.2.
Ethical Review
The investigator must give assurance that the ERB was properly constituted and convened as 
required by International Conference on Harmonisation (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 IB and updates during the course of the study

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.

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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.
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 
electronic case report forms (eCRFs), 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 eCRF 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.
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, 

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applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
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 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 third party organization (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 directly via an electronic patient 
reported outcome (ePRO) diary as part of an ePRO/Clinical Outcome Assessment (COA) 
system. Patient-rated scales/questionnaires will be collected directly via an ePRO tablet device 
at each visit. Data entered into the ePRO/COA system will serve as the source data. 
If ePRO/COA 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 ePRO/COA 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 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 the Lilly, or its designee (clinical 
research physician/clinical research scientist [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 = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; IgM = immunoglobulin M; 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.

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Appendix 5.
Protocol Amendment I5Q-JE-CGAN(a) 
Summary:  A Randomized, Double-Blind, Placebo-
Controlled Study of LY2951742 (Galcanezumab) in 
Japanese Patients with Episodic Migraine
Overview
Protocol I5Q-JE-CGAN [A Randomized, Double-Blind, Placebo-Controlled Study of 
LY2951742 (Galcanezumab) in Japanese Patients with Episodic Migraine] has been amended.  
The new protocol is indicated by amendment (a) and will be used to conduct the study in place of 
any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are as follows:

Added description about observation of patients after second dosing for post-injection 
safety monitoring.

Deleted “signed assent from the patients” from inclusion criterion [6] because patients 
aged 18 and 19 years old are considered old enough to understand the informed consent 
document without any additional assent document.

Changed the description of inclusion criteria [8] and [9] and exclusion criteria [13], [14],
and [15] in order to clarify patient eligibility for the investigators.

Revised description regarding the prefilled syringes since they are not currently certified
in Japan.

Updated abbreviation list: “IUD” and “IUS” added.

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
2.
Schedule of Activities
Serum Pregnancy (for women 
of childbearing potential)i or 
FSH at Visit 1 (all other female
patients for women who have 
evidence of cessation of menses 
for at least 12 months)i
k Patients will receive injections of placebo or galcanezumab after all other visit procedures are completed.  
Following the first dose at Visit 3, patients will be observed for at least 30 minutes in the office 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.
5.1. Overall Design
Study Period III:
At Visit 3 (first dose), patients will be required to remain at the site in the office 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. Patients will continue to log in and complete the ePRO diary each day.
6.1. Inclusion Criteria
[6]
Are able and willing to give signed informed consent, and signed assent from 
the patients and in the case of patients under 20 years old, informed consent 
signed by a parent or guardian. in the case of patients under 20 years old
[8]
Women of child-bearing 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 
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),

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LY2951742 (galcanezumab)
Or
3) Confirmed that all partners have had a vasectomy or tubal ligation AND 
have no fertile sperm base on multiple semen examinations, as shown by
their medical record.
[9]
All patients, male and female, 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 
include 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 [8], or for male patients 
who meet the criterion defined in definition 3) of inclusion criterion [8].
implantable contraceptives; injectable contraceptives; a contraceptive patch; 
barrier methods, such as diaphragms with contraceptive jelly, cervical caps 
with contraceptive jelly, condoms with contraceptive foam, or intrauterine 
devices; a partner with vasectomy.  Birth control is not required if the female 
is infertile due to surgical sterilization (at least 6 weeks after surgical bilateral 
oophorectomy, hysterectomy, or at least 6 weeks after tubal ligation) 
confirmed by medical history or menopause.  Menopause is defined as 
spontaneous amenorrhea for at least 12 months, not induced by a medical 
condition, or spontaneous amenorrhea of 6-12 months and a follicle 
stimulating hormone (FSH) level >40 mIU/mL.
6.2. Exclusion Criteria
[13] Current use or prior exposure to galcanezumab, or another other antibodies to
CGRP antibody or its receptor, including those who have previously 
completed or withdrawn from this study or any other study investigating a 
antibodies to CGRP or its receptor antibody.
[14] Patients who are taking, or are expected to take, therapeutic antibodies 
(including chimeric antibodies) during the course of the study (for example, 
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
[15] Known hypersensitivity to multiple drugs, monoclonal antibodies or other 
therapeutic proteins, or to galcanezumab and the excipients in the 
investigational product.
7.1.2. Medical Devices
The manufactured medical devices provided for use in the study are prefilled syringes, which are 
not certified devices in Japan.

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Appendix 1
Abbreviations and Definitions
IUD
intrauterine device
IUS
intrauterine system