CONQUER: A Study of Galcanezumab (LY2951742) in Adults With Treatment-Resistant Migraine

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03559257
• Collaborator: (none)
• Enrollment: 463
• Locations: 69
• Arms: 2
• Actual Duration (Months): 13.6
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of galcanezumab in people with treatment-resistant episodic or chronic migraine.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Galcanezumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 463 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Adults With Treatment-Resistant Migraine - the CONQUER Study
• Actual Study Start Date: Jul 31, 2018
• Actual Primary Completion Date: Jun 19, 2019
• Actual Study Completion Date: Sep 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galcanezumab Galcanezumab administered subcutaneously (SC).	Drug: Galcanezumab; Administered SC.; Other Names: LY2951742
Placebo Comparator: Placebo Placebo administered SC.	Drug: Placebo; Administered SC.

Outcome Measures

Primary Outcome Measures

1. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 3 from mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

Secondary Outcome Measures

1. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days in Participants With Episodic Migraine [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

2. Percentage of Participants With ≥50% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

3. Percentage of Participants With Episodic Migraine With ≥50% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

4. Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) [Baseline, Month 3]

   MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.

5. Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) in Participants With Episodic Migraine [Baseline, Month 3]

   MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.

6. Percentage of Participants With Episodic Migraine With ≥75% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

7. Percentage of Participants With Episodic Migraine With 100% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

8. Percentage of Participants With ≥75% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

9. Percentage of Participants With 100% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 3]

   MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.

10. Overall Mean Change From Baseline in the Number of Monthly Days With Acute Headache Medication Use [Baseline, Month 1 through Month 3]

    Overall mean is derived from the average of months 1 to 3 from Mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

11. Overall Mean Change From Baseline in the Number of Monthly Headache Days [Baseline, Month 1 through Month 3]

    Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache). Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

12. Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score [Baseline, Month 3]

    The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missed or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LS mean was calculated using analysis of covariance (ANCOVA) with last observation carried forward (LOCF), with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

13. Mean Change From Baseline in the 4-item Migraine Interictal Burden Scale (MIBS-4) [Baseline, Month 3]

    MIBS-4 is a self-administered scale that measures the burden related to headache in the time between attacks. The instrument consists of 4 items that address disruption at work and school, diminished family and social life, difficulty planning, and emotional difficulty. The questionnaire specifically asks about the effect of the disease over the past 4 weeks on days without a headache attack. Response options include: don't know/not applicable (0), never (0), rarely (1), some of the time (2), much of the time (3), or most or all of the time (3). Each responses associated numerical score are summed across all 4 items resulting in a total score ranging from 0 to 12, and the level of interictal burden being categorized into the following: 0 for none, 1-2 mild, 3-4 moderate, and >5 severe. LS mean was calculated using MMRM model with fixed effects of treatment, pooled country, baseline migraine frequency category, month, treatment by month as fixed effects.

14. Mean Change From Baseline in the Work Productivity and Activity Impairment Questionnaire (WPAI) [Baseline, Month 3]

    The WPAI Questionnaire is a patient-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores are calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores are calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, i.e, worse outcomes. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

15. Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) [Baseline, Month 3]

    The PGI-S is a patient-rated instrument that measures illness severity. For this study, the patient was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" The PGI-S includes a range of possible responses, from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

16. Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (US) [Baseline, Month 3]

    EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

17. Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (UK) [Baseline, Month 3]

    EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the UK algorithm (-0.594 to 1). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

18. Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - VAS Score [Baseline, Month 3]

    EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. . The second part is assessed using a visual analog scale (VAS) on which the patient rates their perceived health state, ranging from 0 (the worst health you can imagine) to 100 (the best health you can imagine). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of migraine or chronic migraine.

• History of migraine headaches at least 1 year prior to screening, with onset prior to age 50.

• History of at least 4 migraine headache days and at, with at least 1 headache-free day per month on average within the past 3 months.

• Have documentation of 2 to 4 migraine preventive medication category failures due to inadequate efficacy or tolerability, in the past 10 years.

Exclusion Criteria:

• Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product.

• Current use or prior exposure to galcanezumab or another calcitonin gene-related peptide (CGRP) antibody.

• 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).

• Pregnant or nursing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	21st Century Neurology	Phoenix	Arizona	United States	85004
2	Medical Center for Clinical Research	San Diego	California	United States	92108
3	Sensible Healthcare	Ocoee	Florida	United States	34761
4	University of South Florida	Tampa	Florida	United States	33612
5	Renstar Medical Research	Wesley Chapel	Florida	United States	33544
6	Boston Clinical Trials	Boston	Massachusetts	United States	02131
7	Michigan Head, Pain and Neurological Institute	Ann Arbor	Michigan	United States	48104
8	Clinical Research Institute	Minneapolis	Minnesota	United States	55402
9	Healthy Perspectives Innovative Mental Health Services, PL	Nashua	New Hampshire	United States	03060
10	Bio Behavioral Health	Toms River	New Jersey	United States	08755
11	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
12	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
13	PharmQuest	Greensboro	North Carolina	United States	27408
14	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
15	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina	United States	29464
16	Foothill Family Clinic	Salt Lake City	Utah	United States	84109
17	Health Research of Hampton Roads Inc	Newport News	Virginia	United States	23606
18	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
19	Algemeen Ziekenhuis St Jan Brugge	Brugge		Belgium	8000
20	Universitair Ziekenhuis Brussel	Brussel		Belgium	1090
21	Universitair Ziekenhuis Gent	Gent		Belgium	B-9000
22	Okanagan Clinical Trials	Kelowna	British Columbia	Canada	V1Y 1Z9
23	Aggarwal and Associates Ltd	Brampton	Ontario	Canada	L6T 0G1
24	DIEX Recherche Sherbrooke, Inc	Sherbrooke	Quebec	Canada	J1H 1Z1
25	Clintrial, s.r.o.	Praha 10	Hl. M. Praha	Czechia	100 00
26	Neurologicka ambulance, Neurologie Brno s.r.o.	Brno		Czechia	616 00
27	Brain-Soultherapy s.r.o	Kladno		Czechia	27201
28	DADO MEDICAL, s.r.o.	Praha 2		Czechia	120 00
29	Neurologicka ordinace	Praha 6		Czechia	160 00
30	Institut Neuropsychiatricke Pece	Praha 8		Czechia	18600
31	CHRU de Lille- Hôpital Roger Salengro	Lille	Cedex	France	59037
32	Hôpital de Cimiez	Nice		France	06000
33	CHU St Etienne Hopital Nord	Saint Etienne Cedex 2		France	42000
34	DRK-Kliniken Nordhessen	Kassel	Hessen	Germany	34121
35	Praxis Dr. Philipp Stude	Bochum	Nordrhein-Westfalen	Germany	44787
36	Universitätsklinikum Jena	Jena	Thüringen	Germany	07747
37	Charité Universitätsmedizin Berlin	Berlin		Germany	10117
38	Universitätsklinikum Essen	Essen		Germany	45147
39	Valeomed Kft.	Esztergom	Komarom-Esztergom	Hungary	2500
40	SE Neurologiai Klinika	Budapest		Hungary	1083
41	Orszagos Idegtudomanyi Intezet	Budapest		Hungary	1145
42	Higashi Sapporo Neurology and Neurosurgery Clinic	Sapporo	Hokkaido	Japan	003-0003
43	Medical corporation Shinmatsudakai Atago Hospital	Kochi-Shi	Kochi	Japan	780-0051
44	Sendai Headache and Neurology Clinic	Sendai	Miyagi	Japan	982-0014
45	Takase internal medicine clinic	Toyonaka-shi	Osaka	Japan	560-0012
46	Dokkyo Medical University Hospital	Shimotsuga-Gun	Tochigi	Japan	321 0293
47	Fukuuchi Pain Clinic	Shinjuku-ku	Tokyo	Japan	160-0017
48	Shimoda Neurology Clinic	Tottori-shi	Tottori	Japan	680-0045
49	Doi Clinic Internal Medicine Neurology	Hiroshima		Japan	730-0031
50	Tanaka neurosurgical clinic	Kagoshima		Japan	892-0844
51	Tatsuoka Neurology Clinic	Kyoto		Japan	600-8811
52	Ooba Clinic for Neurosurgery & Headache	Oita		Japan	870-0831
53	Tominaga Hospital	Osaka		Japan	5560017
54	Nowon Eulji Medical Center, Eulji University	Seoul		Korea, Republic of	01830
55	Seoul National University Hospital	Seoul		Korea, Republic of	03080
56	Kangbuk Samsung Hosp	Seoul		Korea, Republic of	03181
57	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	120-792
58	Canisius-Wilhelmina Ziekenhuis	Nijmegen	Gelderland	Netherlands	6532 SZ
59	Isala Klinieken	Zwolle		Netherlands	8025 AB
60	Instituto de Neurologia Dra. Ivonne Fraga	San Juan		Puerto Rico	00918
61	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona	Spain	08907
62	Hospital Universitario Marques De Valdecilla	Santander	Cantabria	Spain	39008
63	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
64	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
65	Hospital Universitario La Fe de Valencia	Valencia		Spain	46026
66	Hospital Clinico Universitario de Valladolid	Valladolid		Spain	47010
67	Hull Royal Infirmary	Hull	East Yorkshire	United Kingdom	HU3 2JZ
68	Kings College Hospital	London	Greater London	United Kingdom	SE5 9RS
69	St Thomas's Hospital	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Mar 22, 2018
• Statistical Analysis Plan - Jul 8, 2019

More Information

Additional Information:

• A Study of Galcanezumab (LY2951742) in Adults With Treatment-Resistant Migraine

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03559257
• Other Study ID Numbers: 16670; I5Q-MC-CGAW; 2018-000600-42
• First Posted: Jun 18, 2018
• Last Update Posted: Jul 8, 2020
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: prevention; prophylaxis; headache; treatment-resistant; treatment resistant
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Arm/Group Title	Placebo/Galcanezumab 120mg	Galcanezumab 120mg
Arm/Group Description	Participants received matching placebo every month for three months by subcutaneous injection (SC) during double blind treatment phase. Participants received initial loading dose of 240mg galcanezumab followed by 120mg every month for two months by SC injection during open label treatment period.	Participants received initial loading dose of 240mg of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection during double blind treatment period. Participants received 120mg of galcanezumab every month for three months by SC injection during open label treatment period.
Period Title: Double Blind Treatment Period
STARTED	230	233
Received at Least One Dose of Study Drug	230	232
COMPLETED	226	225
NOT COMPLETED	4	8
Period Title: Double Blind Treatment Period
STARTED	225	224
COMPLETED	215	217
NOT COMPLETED	10	7

Baseline Characteristics

Arm/Group Title	Placebo/Galcanezumab 120mg	Galcanezumab 120mg	Total
Arm/Group Description	Participants received matching placebo every month for three months by subcutaneous injection (SC) during double blind treatment phase. Participants received initial loading dose of 240mg galcanezumab followed by 120mg every month for two months by SC injection during open label treatment period.	Participants received initial loading dose of 240mg of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection during double blind treatment period. Participants received 120mg of galcanezumab every month for three months by SC injection during open label treatment period.	Total of all reporting groups
Overall Participants	230	232	462
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.67 (12.33)	45.87 (11.34)	45.77 (11.83)
Sex: Female, Male (Count of Participants)
Female	202 87.8%	195 84.1%	397 85.9%
Male	28 12.2%	37 15.9%	65 14.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 7%	15 6.5%	31 6.7%
Not Hispanic or Latino	174 75.7%	172 74.1%	346 74.9%
Unknown or Not Reported	40 17.4%	45 19.4%	85 18.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Asian	35 15.2%	37 15.9%	72 15.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	1 0.2%
Black or African American	2 0.9%	3 1.3%	5 1.1%
White	182 79.1%	183 78.9%	365 79%
More than one race	3 1.3%	0 0%	3 0.6%
Unknown or Not Reported	7 3%	8 3.4%	15 3.2%
Monthly Migraine Headache Days (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	13.01 (5.73)	13.44 (6.08)	13.23 (5.91)

Outcome Measures

1. Primary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days
Description	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 3 from mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg Galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Least Squares Mean (Standard Error) [Days]	-1.02 (0.32)	-4.14 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95%; -3.92 to -2.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.41
	Estimation Comments

2. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days in Participants With Episodic Migraine
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized episodic migraine participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	132	137
Least Squares Mean (Standard Error) [Days]	-0.31 (0.34)	-2.88 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.57
	Confidence Interval	(2-Sided) 95%; -3.41 to -1.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.43
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With ≥50% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Number (95% Confidence Interval) [Percentage of Participants]	13.3 5.8%	37.7 16.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.935
	Confidence Interval	(2-Sided) 95%; 2.719 to 5.693
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Episodic Migraine With ≥50% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized episodic migraine participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	132	137
Number (95% Confidence Interval) [Percentage of Participants]	17.1 7.4%	41.8 18%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.481
	Confidence Interval	(2-Sided) 95%; 2.252 to 5.381
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1)
Description	MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3. LS Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	222	223
Least Squares Mean (Standard Error) [score on a scale]	10.68 (1.34)	23.21 (1.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	12.53
	Confidence Interval	(2-Sided) 95%; 9.19 to 15.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.70
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) in Participants With Episodic Migraine
Description	MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized episodic migraine participants who received at least one dose of study drug and had a post baseline value at Month 3. LS Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	127	135
Least Squares Mean (Standard Error) [score on a scale]	11.88 (1.80)	23.39 (1.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	11.51
	Confidence Interval	(2-Sided) 95%; 7.14 to 15.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.22
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Episodic Migraine With ≥75% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized episodic migraine participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	132	137
Number (95% Confidence Interval) [Percentage of Participants]	3.7 1.6%	18.4 7.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.878
	Confidence Interval	(2-Sided) 95%; 2.374 to 14.554
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Episodic Migraine With 100% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized episodic migraine participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	132	137
Number (95% Confidence Interval) [Percentage of Participants]	0.00 0%	7.7 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	999.999
	Confidence Interval	(2-Sided) 95%; 548.706 to 999.999
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value and upper bound are >999.999

9. Secondary Outcome

Title	Percentage of Participants With ≥75% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Number (95% Confidence Interval) [Percentage of Participants]	3.3 1.4%	14.5 6.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.012
	Confidence Interval	(2-Sided) 95%; 2.352 to 10.679
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With 100% Reduction From Baseline in Monthly Migraine Headache Days
Description	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Number (95% Confidence Interval) [Percentage of Participants]	0.000 0%	4.9 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Pseudo likelihood-based repeated measure
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	999.99
	Confidence Interval	(2-Sided) 95%; 999.99 to 999.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate, upper limit and lower limit are >999.99

11. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Days With Acute Headache Medication Use
Description	Overall mean is derived from the average of months 1 to 3 from Mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Least Squares Mean (Standard Error) [Days]	-0.80 (0.31)	-4.19 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.40
	Confidence Interval	(2-Sided) 95%; -4.14 to -2.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.38
	Estimation Comments

12. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Headache Days
Description	Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache). Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.
Time Frame	Baseline, Month 1 through Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	228	230
Least Squares Mean (Standard Error) [Days]	-1.05 (0.36)	-4.18 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.13
	Confidence Interval	(2-Sided) 95%; -3.96 to -2.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments

13. Secondary Outcome

Title	Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score
Description	The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missed or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LS mean was calculated using analysis of covariance (ANCOVA) with last observation carried forward (LOCF), with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	228
Least Squares Mean (Standard Error) [score on a scale]	-3.295 (3.2834)	-21.097 (3.3164)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

14. Secondary Outcome

Title	Mean Change From Baseline in the 4-item Migraine Interictal Burden Scale (MIBS-4)
Description	MIBS-4 is a self-administered scale that measures the burden related to headache in the time between attacks. The instrument consists of 4 items that address disruption at work and school, diminished family and social life, difficulty planning, and emotional difficulty. The questionnaire specifically asks about the effect of the disease over the past 4 weeks on days without a headache attack. Response options include: don't know/not applicable (0), never (0), rarely (1), some of the time (2), much of the time (3), or most or all of the time (3). Each responses associated numerical score are summed across all 4 items resulting in a total score ranging from 0 to 12, and the level of interictal burden being categorized into the following: 0 for none, 1-2 mild, 3-4 moderate, and >5 severe. LS mean was calculated using MMRM model with fixed effects of treatment, pooled country, baseline migraine frequency category, month, treatment by month as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	222	223
Least Squares Mean (Standard Error) [score on a scale]	-0.78 (0.21)	-1.83 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -1.58 to -0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

15. Secondary Outcome

Title	Mean Change From Baseline in the Work Productivity and Activity Impairment Questionnaire (WPAI)
Description	The WPAI Questionnaire is a patient-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores are calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores are calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, i.e, worse outcomes. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	227
Activity Impairment	-8.644 (1.9195)	-20.713 (1.9537)
Absenteeism	-2.900 (1.2436)	-4.224 (1.2929)
Presenteeism	-2.564 (2.3222)	-12.504 (2.3705)
Work Impairment	-3.457 (2.4098)	-14.307 (2.5148)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	Activity Impairment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	Absenteeism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3880
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	Presenteeism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	Work impairment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments

16. Secondary Outcome

Title	Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S)
Description	The PGI-S is a patient-rated instrument that measures illness severity. For this study, the patient was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" The PGI-S includes a range of possible responses, from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	228
Least Squares Mean (Standard Error) [score on a scale]	-0.283 (0.0863)	-0.664 (0.0873)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments

17. Secondary Outcome

Title	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (US)
Description	EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	227
Least Squares Mean (Standard Error) [score on a scale]	-0.002 (0.0079)	0.013 (0.0080)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1267
	Comments
	Method	ANCOVA
	Comments

18. Secondary Outcome

Title	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (UK)
Description	EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the UK algorithm (-0.594 to 1). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	227
Least Squares Mean (Standard Error) [score on a scale]	-0.001 (0.0109)	0.017 (0.0110)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1630
	Comments
	Method	ANCOVA
	Comments

19. Secondary Outcome

Title	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - VAS Score
Description	EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. . The second part is assessed using a visual analog scale (VAS) on which the patient rates their perceived health state, ranging from 0 (the worst health you can imagine) to 100 (the best health you can imagine). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had a post baseline value at Month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.	Participants received initial loading dose of 240 milligrams (mg) of galcanezumab followed by 120mg galcanezumab every month for two months by SC injection.
Measure Participants	225	227
Least Squares Mean (Standard Error) [mm]	-0.086 (1.2916)	3.376 (1.3080)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0277
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Up to 6 months
Adverse Event Reporting Description	Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Arm/Group Title	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase		Placebo/Galcanezumab 120mg - Open-Label Treatment Phase		Galcanezumab 120mg/Galcanezumab 120mg - Open-Label Treatment
Arm/Group Description	Participants received matching placebo every month for three months by SC injection.		Participants received initial loading dose of 240 milligrams (mg) of Galcanezumab followed by 120mg Galcanezumab every month for two months by SC injection.		Participants received initial loading dose of 240mg Galcanezumab followed by 120mg every month for two months by SC injection.		Participants received 120mg of Galcanezumab every month for three months by SC injection.
All Cause Mortality
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase		Placebo/Galcanezumab 120mg - Open-Label Treatment Phase		Galcanezumab 120mg/Galcanezumab 120mg - Open-Label Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/230 (0%)		0/232 (0%)		0/225 (0%)		0/224 (0%)
Serious Adverse Events
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase		Placebo/Galcanezumab 120mg - Open-Label Treatment Phase		Galcanezumab 120mg/Galcanezumab 120mg - Open-Label Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/230 (0.9%)		2/232 (0.9%)		6/225 (2.7%)		3/224 (1.3%)
Gastrointestinal disorders
Haemorrhoids	0/230 (0%)	0	1/232 (0.4%)	1	0/225 (0%)	0	0/224 (0%)	0
Inguinal hernia	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
General disorders
Asthenia	0/230 (0%)	0	0/232 (0%)	0	0/225 (0%)	0	1/224 (0.4%)	1
Pain	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
Infections and infestations
Pneumonia	0/230 (0%)	0	0/232 (0%)	0	0/225 (0%)	0	1/224 (0.4%)	1
Tonsillitis	0/230 (0%)	0	1/232 (0.4%)	1	0/225 (0%)	0	0/224 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
Injury	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
Lower limb fracture	1/230 (0.4%)	1	0/232 (0%)	0	0/225 (0%)	0	0/224 (0%)	0
Nervous system disorders
Hemiplegia	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
Reproductive system and breast disorders
Ovarian cyst ruptured	0/202 (0%)	0	0/195 (0%)	0	0/197 (0%)	0	1/187 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/230 (0%)	0	0/232 (0%)	0	1/225 (0.4%)	1	0/224 (0%)	0
Vascular disorders
Behcet's syndrome	1/230 (0.4%)	1	0/232 (0%)	0	0/225 (0%)	0	0/224 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase		Placebo/Galcanezumab 120mg - Open-Label Treatment Phase		Galcanezumab 120mg/Galcanezumab 120mg - Open-Label Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/230 (13.5%)		21/232 (9.1%)		19/225 (8.4%)		13/224 (5.8%)
General disorders
Injection site pain	13/230 (5.7%)	30	5/232 (2.2%)	7	11/225 (4.9%)	19	5/224 (2.2%)	7
Infections and infestations
Nasopharyngitis	21/230 (9.1%)	24	16/232 (6.9%)	17	11/225 (4.9%)	11	8/224 (3.6%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.