Evaluation of Efficay & Safety of Galcanezumab in the Prevention of Episodic Migraine- the EVOLVE-2 Study

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02614196
• Collaborator: (none)
• Enrollment: 986
• Locations: 113
• Arms: 6
• Actual Duration (Months): 34
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as galcanezumab in participants with episodic migraine.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 986 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Sponsor is also masked.
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Episodic Migraine - the EVOLVE-2 Study
• Actual Study Start Date: Dec 4, 2015
• Actual Primary Completion Date: Mar 29, 2017
• Actual Study Completion Date: Oct 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galcanezumab 120mg Galcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Experimental: Galcanezumab 240mg Galcanezumab 240mg given by SC injection once a month for 6 months.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Placebo Comparator: Placebo Placebo given by SC injection once a month for 6 months.	Drug: Placebo; Administered SC
Experimental: Galcanezumab 120mg Maximum Extended Enrollment Cohort Galcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Experimental: Galcanezumab 240mg Maximum Extended Enrollment Cohort Galcanezumab 240mg given by SC injection once a month for 6 months.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Placebo Comparator: Placebo Maximum Extended Enrollment Cohort Placebo given by SC injection once a month for 6 months.	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 6]

   Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. 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 one of the following: Nausea and/or vomiting; Photophobia and phonophobia; Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects.

Secondary Outcome Measures

1. Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline.

2. Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain [Baseline, Month 4 through Month 6]

   MSQ v2.1 was developed to address physical & emotional limitations of specific concern to individuals with migraine. 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. Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month & baseline MHD category as fixed factors.

3. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache [Baseline, Month 1 through Month 6]

   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 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.

4. Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating [Baseline, Month 4 through Month 6]

   The PGI-S scale is a participant-rated instrument that measures patients own global impression of their illness severity. The participant was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options were from 1 ("normal, not at all ill") to 7 ("extremely ill"). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.

5. Overall Mean Change From Baseline in Headache Hours [Baseline, Month 1 through Month 6]

   Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category.

6. Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score [Baseline, Month 6]

   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 missing 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. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.

7. Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab [Month 1 through Month 6]

   Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20.

8. Pharmacokinetics (PK): Serum Concentrations of Galcanezumab [Month 6]

   Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.

9. Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) [Month 6]

   Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta version (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, migraine onset prior to age 50 and MONTHLY frequency of 4-14 MHD.

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.

• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to galcanezumab.

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	21st Century Neurology	Phoenix	Arizona	United States	85004
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	Axiom Research	Apple Valley	California	United States	92307
4	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
5	Catalina Research Institute, LLC	Montclair	California	United States	91763
6	Pacific Research Partners, LLC	Oakland	California	United States	94607
7	Medical Center for Clinical Research	San Diego	California	United States	92108
8	Optimus Medical Group	San Francisco	California	United States	94102
9	Schuster Medical Research Institute	Sherman Oaks	California	United States	91403
10	IMMUNOe International Research Centers	Centennial	Colorado	United States	80112
11	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
12	Sunrise Clinical Research	Hollywood	Florida	United States	33021
13	Westside Center for Clinical Research	Jacksonville	Florida	United States	32205
14	Clinical Neuroscience Solutions Inc	Jacksonville	Florida	United States	32256
15	Sensible Healthcare	Ocoee	Florida	United States	34761
16	Meridien Research	Tampa	Florida	United States	33634
17	Atlanta Center of Medical Research	Atlanta	Georgia	United States	30331
18	Christie Clinic, LLC	Champaign	Illinois	United States	61820
19	Diamond Headache Clinic	Chicago	Illinois	United States	60642
20	Josephson Wallack Munshower Neurology	Indianapolis	Indiana	United States	46256
21	Heartland Research Associates	Wichita	Kansas	United States	67205
22	Novex Clinical Research	New Bedford	Massachusetts	United States	02740
23	QUEST Research Institute	Farmington Hills	Michigan	United States	48334
24	Healthcare Research Network - Hazelwood	Hazelwood	Missouri	United States	63042
25	Nevada Headache Institute	Las Vegas	Nevada	United States	89113
26	Bio Behavioral Health	Toms River	New Jersey	United States	08755
27	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
28	Regional Clinical Research	Binghamton	New York	United States	13760
29	SPRI Clinical Trials, LLC.	Brooklyn	New York	United States	11235
30	High Point Clinical Trials Center	High Point	North Carolina	United States	27265
31	Neurology & Neuroscience Associates, Inc.	Akron	Ohio	United States	44320
32	Univ of Cincinnati College of Medicine	Cincinnati	Ohio	United States	45219
33	Urgent Care Specialists, LLC	Columbus	Ohio	United States	43214
34	Urgent Care Specialists, LLC	Dayton	Ohio	United States	45424
35	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
36	Oregon Neurology Associates	Springfield	Oregon	United States	97477
37	Clinical Research of Philadelphia	Philadelphia	Pennsylvania	United States	19114
38	Mountain View Clinical Research, Inc	Greer	South Carolina	United States	29651
39	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina	United States	29464
40	FutureSearch Trials	Dallas	Texas	United States	75231
41	Clinical Trial Network	Houston	Texas	United States	77074
42	Clinpoint Trial, LLC	Waxahachie	Texas	United States	75165
43	Foothill Family Clinic	Salt Lake City	Utah	United States	84109
44	Jordan River Family Medicine	South Jordan	Utah	United States	84095
45	Health Research of Hampton Roads Inc	Newport News	Virginia	United States	23606
46	Sentara Neurology Specialists	Virginia Beach	Virginia	United States	23456
47	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
48	Polyclinic	Seattle	Washington	United States	98104
49	Dean Foundation for Health Research and Education	Middleton	Wisconsin	United States	53562
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ciudad Autonoma de Buenos Aires		Argentina	C1046AAQ
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ciudad Autonoma de Buenos Aire		Argentina	C1012AAR
52	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ciudad Autonoma de Buenos Aire		Argentina	C1013AAB
53	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ciudad Autonoma de Buenos Aire		Argentina	C1128AAF
54	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brno		Czechia	656 91
55	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kladno		Czechia	27201
56	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Praha 10		Czechia	100 00
57	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Praha 2		Czechia	120 00
58	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Praha 6		Czechia	160 00
59	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Praha 8		Czechia	182 00
60	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	10117
61	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bielefeld		Germany	33647
62	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bochum		Germany	44787
63	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bochum		Germany	44797
64	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Essen		Germany	45147
65	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Halle		Germany	06120
66	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	20246
67	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Jena		Germany	07747
68	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kassel		Germany	34121
69	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Königstein		Germany	61462
70	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Prien		Germany	83209
71	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tübingen		Germany	72076
72	Hillel Yaffe	Hadera		Israel	38100
73	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Haifa		Israel	3525408
74	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kfar Saba		Israel	4420122
75	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ramat Gan		Israel	5266202
76	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hwaseong-si		Korea, Republic of	18450
77	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Seoul		Korea, Republic of	01830
78	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Seoul		Korea, Republic of	03080
79	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul		Korea, Republic of	03181
80	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Seoul		Korea, Republic of	06351
81	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul		Korea, Republic of	07441
82	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Seoul		Korea, Republic of	08308
83	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Aguascalientes		Mexico	20217
84	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Culiacan		Mexico	80020
85	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Merida		Mexico	97070
86	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	03740
87	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	México City		Mexico	03310
88	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Amsterdam		Netherlands	1078 VV
89	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Geleen		Netherlands	6162 BG
90	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leiden		Netherlands	2333 ZA
91	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nijmegen		Netherlands	6532 SZ
92	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tilburg		Netherlands	5042 AD
93	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zwolle		Netherlands	8025 AB
94	Cortex, PSC	Las Piedras		Puerto Rico	00771
95	SomniCare Sleep Institute	San Juan		Puerto Rico	00918
96	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08035
97	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08907
98	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Elda		Spain	03600
99	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Santander		Spain	39008
100	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Valencia		Spain	46010
101	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Valencia		Spain	46026
102	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Valladolid		Spain	47005
103	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kaohsiung		Taiwan	80756
104	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taichung		Taiwan	43761
105	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tainan		Taiwan	70142
106	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tainan		Taiwan	71004
107	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei		Taiwan	11217
108	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei		Taiwan	220
109	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Glasgow		United Kingdom	G51 4TF
110	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hull		United Kingdom	HU3 2JZ
111	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Liverpool		United Kingdom	L9 7LJ
112	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	London		United Kingdom	SE5 9RS
113	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stoke-on-Trent		United Kingdom	ST4 6QG

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 - Jan 22, 2016
• Statistical Analysis Plan - Apr 25, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02614196
• Other Study ID Numbers: 15768; I5Q-MC-CGAH; 2015-001882-17
• First Posted: Nov 25, 2015
• Last Update Posted: Jun 17, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Eli Lilly and Company: prevention; prophylaxis; headache
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg	Placebo Maximum Extended Enrollment Cohort	Galcanezumab 120mg Maximum Extended Enrollment Cohort	Galcanezumab 240mg Maximum Extended Enrollment Cohort
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.
Period Title: Double Blind Treatment Phase
STARTED	463	233	226	30	15	19
Received at Least One Dose of Study Drug	461	231	223	30	14	19
COMPLETED	387	203	195	26	14	19
NOT COMPLETED	76	30	31	4	1	0
Period Title: Double Blind Treatment Phase
STARTED	410	213	207	25	15	19
COMPLETED	390	208	199	24	13	19
NOT COMPLETED	20	5	8	1	2	0

Baseline Characteristics

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg	Placebo Maximum Extended Enrollment Cohort	Galcanezumab 120mg Maximum Extended Enrollment Cohort	Galcanezumab 240mg Maximum Extended Enrollment Cohort	Total
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase. Participants did not receive any intervention during post-treatment follow-up phase.	Total of all reporting groups
Overall Participants	461	231	223	30	15	19	979
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.33 (11.30)	40.91 (11.15)	41.91 (10.77)	45.37 (10.30)	39.40 (11.58)	42.58 (11.13)	41.95 (11.12)
Sex: Female, Male (Count of Participants)
Female	393 85.2%	197 85.3%	191 85.7%	22 73.3%	13 86.7%	14 73.7%	830 84.8%
Male	68 14.8%	34 14.7%	32 14.3%	8 26.7%	2 13.3%	5 26.3%	149 15.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	118 25.6%	58 25.1%	61 27.4%	4 13.3%	2 13.3%	3 15.8%	246 25.1%
Not Hispanic or Latino	318 69%	162 70.1%	151 67.7%	21 70%	10 66.7%	12 63.2%	674 68.8%
Unknown or Not Reported	25 5.4%	11 4.8%	11 4.9%	5 16.7%	3 20%	4 21.1%	59 6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	20 4.3%	8 3.5%	13 5.8%	0 0%	0 0%	0 0%	41 4.2%
Asian	50 10.8%	28 12.1%	24 10.8%	30 100%	15 100%	19 100%	166 17%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	2 0.9%	0 0%	0 0%	0 0%	2 0.2%
Black or African American	36 7.8%	11 4.8%	16 7.2%	0 0%	0 0%	0 0%	63 6.4%
White	325 70.5%	166 71.9%	152 68.2%	0 0%	0 0%	0 0%	643 65.7%
More than one race	30 6.5%	18 7.8%	16 7.2%	0 0%	0 0%	0 0%	64 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Argentina	22 4.8%	12 5.2%	10 4.5%	0 0%	0 0%	0 0%	44 4.5%
South Korea	34 7.4%	17 7.4%	17 7.6%	14 46.7%	7 46.7%	9 47.4%	98 10%
Netherlands	24 5.2%	11 4.8%	11 4.9%	0 0%	0 0%	0 0%	46 4.7%
United States	224 48.6%	112 48.5%	110 49.3%	0 0%	0 0%	0 0%	446 45.6%
Czechia	39 8.5%	19 8.2%	19 8.5%	0 0%	0 0%	0 0%	77 7.9%
Taiwan	12 2.6%	7 3%	5 2.2%	16 53.3%	8 53.3%	10 52.6%	58 5.9%
Mexico	36 7.8%	18 7.8%	17 7.6%	0 0%	0 0%	0 0%	71 7.3%
United Kingdom	8 1.7%	4 1.7%	3 1.3%	0 0%	0 0%	0 0%	15 1.5%
Israel	11 2.4%	5 2.2%	5 2.2%	0 0%	0 0%	0 0%	21 2.1%
Germany	37 8%	19 8.2%	19 8.5%	0 0%	0 0%	0 0%	75 7.7%
Spain	14 3%	7 3%	7 3.1%	0 0%	0 0%	0 0%	28 2.9%
Migraine Headache Days (MHD) per month (Days per Month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days per Month]	9.19 (2.99)	9.07 (2.87)	9.06 (2.92)	9.16 (2.98)	9.06 (2.86)	9.01 (2.90)	9.10 (2.93)

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. 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 one of the following: Nausea and/or vomiting; Photophobia and phonophobia; Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects.
Time Frame	Baseline, Month 1 through Month 6

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. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	450	226	220
Least Squares Mean (Standard Error) [Migraine Headache Days per Month]	-2.28 (0.20)	-4.29 (0.25)	-4.18 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.02
	Confidence Interval	(2-Sided) 95%; -2.55 to -1.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.90
	Confidence Interval	(2-Sided) 95%; -2.44 to -1.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

2. Secondary Outcome

Title	Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days
Description	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline.
Time Frame	Baseline, Month 1 through Month 6

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. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	450	226	220
≥50%	36 (1.7) 7.8%	59.3 (2.4) 25.7%	56.5 (2.5) 25.3%
≥75%	17.8 (1.3) 3.9%	33.5 (2.3) 14.5%	34.3 (2.3) 15.4%
100%	5.7 (0.7) 1.2%	11.5 (1.4) 5%	13.8 (1.5) 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥50%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.60
	Confidence Interval	(2-Sided) 95%; 2.03 to 3.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥50%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95%; 1.81 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥75%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95%; 1.78 to 3.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥75%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; 1.84 to 3.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥100%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95%; 1.50 to 3.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥100%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.67
	Confidence Interval	(2-Sided) 95%; 1.87 to 3.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain
Description	MSQ v2.1 was developed to address physical & emotional limitations of specific concern to individuals with migraine. 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. Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month & baseline MHD category as fixed factors.
Time Frame	Baseline, Month 4 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline & at least one post baseline value. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo subcutaneously once a month for 6 months.	Participants received loading dose of 240mg galcanezumab followed by 120mg galcanezumab once a month for 5 months subcutaneously.	Participants received 240mg galcanezumab subcutaneously once a month for 6 months.
Measure Participants	443	226	219
Least Squares Mean (Standard Error) [units on a scale]	19.65 (0.92)	28.47 (1.15)	27.04 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	8.82
	Confidence Interval	(2-Sided) 95%; 6.33 to 11.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	7.39
	Confidence Interval	(2-Sided) 95%; 4.88 to 9.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.28
	Estimation Comments

4. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache
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 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and post baseline value. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months subcutaneously.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	450	226	220
Least Squares Mean (Standard Error) [Days per Month]	-1.85 (0.18)	-3.67 (0.22)	-3.63 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.82
	Confidence Interval	(2-Sided) 95%; -2.29 to -1.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.78
	Confidence Interval	(2-Sided) 95%; -2.25 to -1.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating
Description	The PGI-S scale is a participant-rated instrument that measures patients own global impression of their illness severity. The participant was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options were from 1 ("normal, not at all ill") to 7 ("extremely ill"). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 4 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and post baseline value. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	443	226	219
Least Squares Mean (Standard Error) [units on a scale]	-0.94 (0.07)	-1.22 (0.08)	-1.17 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.012
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.41 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

6. Secondary Outcome

Title	Overall Mean Change From Baseline in Headache Hours
Description	Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category.
Time Frame	Baseline, Month 1 through Month 6

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. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab followed by 120mg galcanezumab once a month for 5 months subcutaneously.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	450	226	220
Least Squares Mean (Standard Error) [Headache Hours per Month]	-10.89 (1.92)	-26.07 (2.41)	-24.44 (2.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-15.19
	Confidence Interval	(2-Sided) 95%; -20.27 to -10.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.59
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-13.56
	Confidence Interval	(2-Sided) 95%; -18.67 to -8.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.60
	Estimation Comments

7. 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 missing 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. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 6

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. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	409	216	215
Least Squares Mean (Standard Error) [units on a scale]	-12.02 (1.27)	-21.17 (1.58)	-20.24 (1.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-9.15
	Confidence Interval	(2-Sided) 95%; -12.61 to -5.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.76
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-8.22
	Confidence Interval	(2-Sided) 95%; -11.71 to -4.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.78
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab
Description	Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20.
Time Frame	Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug & had least one non-missing test result for ADA for each of the baseline period and the post-baseline period. As pre-specified in the analysis plan, outcome measures will not be reported for the ME2 arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	443	222	214
Number [percentage of participants]	0.45 0.1%	8.56 3.7%	5.14 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	TE ADA Positive.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	TE ADA Positive
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentrations of Galcanezumab
Description	Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had measurable serum concentrations. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months subcutaneous injection.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	194	193
Mean (Standard Deviation) [Nanogram per milliliter (ng/mL)]	17400 (8820)	32200 (12600)

10. Secondary Outcome

Title	Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Description	Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who had received at least one dose of study drug and had measurable plasma concentration. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (ME2) arms/groups but only for the main global study arms/groups.

Arm/Group Title	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Arm/Group Description	Participants received placebo by subcutaneous injection once a month for 6 months.	Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months subcutaneously.	Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Measure Participants	29	187	185
Mean (Standard Deviation) [ng/mL]	0.541 (1.11)	3.93 (1.83)	4.98 (1.60)

Adverse Events

Time Frame	Up to 10 Months
Adverse Event Reporting Description	There were 5 participants in Galcanezumab 120mg treatment phase, 1 participant in Galcanezumab 120mg post- treatment , 1 participant in Galcanezumab 120 mg treatment phase ME2 & 1 participant in Galcanezumab 120mg post-treatment ME2 arms who discontinued after receiving loading dose of 240mg, these participants were included in Galcanezumab 240mg Treatment, Post Treatment & equivalent ME2 arms for adverse event reporting. Per protocol, AE analysis was planned per treatment regimen received.
Arm/Group Title	Placebo - Treatment Phase		Galcanezumab 120mg - Treatment Phase		Galcanezumab 240mg - Treatment Phase		Placebo - Post-treatment Phase		Galcanezumab 120mg - Post-treatment Phase		Galcanezumab 240mg - Post-treatment Phase		Placebo - Treatment Phase ME2		Galcanezumab 120mg - Treatment Phase ME2		Galcanezumab 240mg - Treatment Phase ME2		Placebo - Post-treatment Phase ME2		Galcanezumab 120mg - Post-treatment Phase ME2		Galcanezumab 240mg - Post-treatment Phase ME2
Arm/Group Description	Participants received placebo subcutaneously once a month for 6 months.		Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months subcutaneously.		Participants received 240mg galcanezumab subcutaneously once a month for 6 months.		Participants didn't receive any intervention.		Participants didn't receive any intervention.		Participants didn't receive any intervention.		Participants received placebo subcutaneously once a month for 6 months.		Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months subcutaneously.		Participants received 240mg galcanezumab subcutaneously once a month for 6 months.		Participants didn't receive any intervention.		Participants didn't receive any intervention.		Participants didn't receive any intervention.
All Cause Mortality
	Placebo - Treatment Phase		Galcanezumab 120mg - Treatment Phase		Galcanezumab 240mg - Treatment Phase		Placebo - Post-treatment Phase		Galcanezumab 120mg - Post-treatment Phase		Galcanezumab 240mg - Post-treatment Phase		Placebo - Treatment Phase ME2		Galcanezumab 120mg - Treatment Phase ME2		Galcanezumab 240mg - Treatment Phase ME2		Placebo - Post-treatment Phase ME2		Galcanezumab 120mg - Post-treatment Phase ME2		Galcanezumab 240mg - Post-treatment Phase ME2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/461 (0%)		0/226 (0%)		0/228 (0%)		0/410 (0%)		0/212 (0%)		0/208 (0%)		0/30 (0%)		0/14 (0%)		0/20 (0%)		0/25 (0%)		0/14 (0%)		0/20 (0%)
Serious Adverse Events
	Placebo - Treatment Phase		Galcanezumab 120mg - Treatment Phase		Galcanezumab 240mg - Treatment Phase		Placebo - Post-treatment Phase		Galcanezumab 120mg - Post-treatment Phase		Galcanezumab 240mg - Post-treatment Phase		Placebo - Treatment Phase ME2		Galcanezumab 120mg - Treatment Phase ME2		Galcanezumab 240mg - Treatment Phase ME2		Placebo - Post-treatment Phase ME2		Galcanezumab 120mg - Post-treatment Phase ME2		Galcanezumab 240mg - Post-treatment Phase ME2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/461 (1.1%)		5/226 (2.2%)		7/228 (3.1%)		3/410 (0.7%)		1/212 (0.5%)		3/208 (1.4%)		1/30 (3.3%)		1/14 (7.1%)		0/20 (0%)		2/25 (8%)		0/14 (0%)		0/20 (0%)
Cardiac disorders
Acute myocardial infarction	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Endocrine disorders
Goitre	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders
Gastritis	0/461 (0%)	0	1/226 (0.4%)	1	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Haemorrhoids	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Rectal polyp	0/461 (0%)	0	1/226 (0.4%)	1	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
General disorders
Pyrexia	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/25 (4%)	1	0/14 (0%)	0	0/20 (0%)	0
Cholelithiasis	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Gallbladder polyp	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Infections and infestations
Appendicitis	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Influenza	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Pyelonephritis	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Urosepsis	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Injury, poisoning and procedural complications
Foot fracture	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Meniscus injury	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Rib fracture	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Road traffic accident	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	1/30 (3.3%)	1	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Patellofemoral pain syndrome	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix	0/393 (0%)	0	1/192 (0.5%)	1	0/196 (0%)	0	0/349 (0%)	0	0/179 (0%)	0	0/181 (0%)	0	0/22 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/18 (0%)	0	0/13 (0%)	0	0/14 (0%)	0
Uterine leiomyoma	0/393 (0%)	0	0/192 (0%)	0	0/196 (0%)	0	0/349 (0%)	0	1/179 (0.6%)	1	0/181 (0%)	0	0/22 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/18 (0%)	0	0/13 (0%)	0	0/14 (0%)	0
Nervous system disorders
Generalised tonic-clonic seizure	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Headache	0/461 (0%)	0	1/226 (0.4%)	1	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Migraine	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/25 (4%)	1	0/14 (0%)	0	0/20 (0%)	0
Transient ischaemic attack	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Psychiatric disorders
Disorientation	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Panic attack	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Post-traumatic stress disorder	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Suicide attempt	1/461 (0.2%)	1	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Renal and urinary disorders
Bladder dysfunction	0/461 (0%)	0	1/226 (0.4%)	1	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo - Treatment Phase		Galcanezumab 120mg - Treatment Phase		Galcanezumab 240mg - Treatment Phase		Placebo - Post-treatment Phase		Galcanezumab 120mg - Post-treatment Phase		Galcanezumab 240mg - Post-treatment Phase		Placebo - Treatment Phase ME2		Galcanezumab 120mg - Treatment Phase ME2		Galcanezumab 240mg - Treatment Phase ME2		Placebo - Post-treatment Phase ME2		Galcanezumab 120mg - Post-treatment Phase ME2		Galcanezumab 240mg - Post-treatment Phase ME2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	150/461 (32.5%)		78/226 (34.5%)		87/228 (38.2%)		40/410 (9.8%)		16/212 (7.5%)		13/208 (6.3%)		10/30 (33.3%)		9/14 (64.3%)		9/20 (45%)		3/25 (12%)		6/14 (42.9%)		0/20 (0%)
Gastrointestinal disorders
Abdominal pain upper	3/461 (0.7%)	3	4/226 (1.8%)	5	3/228 (1.3%)	3	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	2	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	1/25 (4%)	1	0/14 (0%)	0	0/20 (0%)	0
Nausea	15/461 (3.3%)	15	4/226 (1.8%)	4	3/228 (1.3%)	3	1/410 (0.2%)	1	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Vomiting	4/461 (0.9%)	4	0/226 (0%)	0	2/228 (0.9%)	2	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
General disorders
Injection site pain	39/461 (8.5%)	142	21/226 (9.3%)	100	20/228 (8.8%)	61	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Injection site reaction	0/461 (0%)	0	7/226 (3.1%)	17	18/228 (7.9%)	25	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	3/20 (15%)	12	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Infections and infestations
Cystitis	5/461 (1.1%)	5	2/226 (0.9%)	2	2/228 (0.9%)	2	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Hordeolum	2/461 (0.4%)	2	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Influenza	14/461 (3%)	16	3/226 (1.3%)	4	9/228 (3.9%)	9	5/410 (1.2%)	5	1/212 (0.5%)	1	1/208 (0.5%)	1	2/30 (6.7%)	2	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Nasopharyngitis	41/461 (8.9%)	49	19/226 (8.4%)	23	16/228 (7%)	21	18/410 (4.4%)	19	5/212 (2.4%)	5	4/208 (1.9%)	5	1/30 (3.3%)	1	2/14 (14.3%)	2	2/20 (10%)	3	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Pharyngitis	1/461 (0.2%)	1	0/226 (0%)	0	1/228 (0.4%)	1	2/410 (0.5%)	2	1/212 (0.5%)	1	1/208 (0.5%)	1	2/30 (6.7%)	2	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Rhinitis	4/461 (0.9%)	4	2/226 (0.9%)	2	1/228 (0.4%)	2	0/410 (0%)	0	1/212 (0.5%)	1	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	1/25 (4%)	1	0/14 (0%)	0	0/20 (0%)	0
Upper respiratory tract infection	16/461 (3.5%)	19	13/226 (5.8%)	14	12/228 (5.3%)	12	3/410 (0.7%)	4	4/212 (1.9%)	5	2/208 (1%)	2	2/30 (6.7%)	2	3/14 (21.4%)	4	1/20 (5%)	1	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Vaginal infection	0/393 (0%)	0	2/192 (1%)	2	1/196 (0.5%)	1	2/349 (0.6%)	2	0/179 (0%)	0	0/181 (0%)	0	0/22 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/18 (0%)	0	0/13 (0%)	0	0/14 (0%)	0
Vulvovaginitis	1/393 (0.3%)	1	0/192 (0%)	0	0/196 (0%)	0	0/349 (0%)	0	0/179 (0%)	0	0/181 (0%)	0	0/22 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/18 (0%)	0	0/13 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Contusion	3/461 (0.7%)	3	1/226 (0.4%)	1	2/228 (0.9%)	2	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	0/14 (0%)	0	2/20 (10%)	2	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Muscle strain	1/461 (0.2%)	1	1/226 (0.4%)	1	1/228 (0.4%)	1	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	5/461 (1.1%)	5	4/226 (1.8%)	4	3/228 (1.3%)	3	1/410 (0.2%)	1	2/212 (0.9%)	2	0/208 (0%)	0	2/30 (6.7%)	2	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Arthritis	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	1/208 (0.5%)	1	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Back pain	20/461 (4.3%)	24	2/226 (0.9%)	2	5/228 (2.2%)	5	4/410 (1%)	4	2/212 (0.9%)	2	1/208 (0.5%)	1	1/30 (3.3%)	1	2/14 (14.3%)	3	0/20 (0%)	0	1/25 (4%)	1	1/14 (7.1%)	1	0/20 (0%)	0
Foot deformity	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Intervertebral disc disorder	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/461 (0%)	0	0/226 (0%)	0	0/228 (0%)	0	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Nervous system disorders
Carpal tunnel syndrome	0/461 (0%)	0	0/226 (0%)	0	1/228 (0.4%)	1	1/410 (0.2%)	1	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Dizziness	10/461 (2.2%)	12	8/226 (3.5%)	10	7/228 (3.1%)	7	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/25 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0
Hypoaesthesia	2/461 (0.4%)	2	0/226 (0%)	0	2/228 (0.9%)	2	0/410 (0%)	0	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	1/25 (4%)	1	0/14 (0%)	0	0/20 (0%)	0
Psychiatric disorders
Insomnia	8/461 (1.7%)	9	3/226 (1.3%)	3	0/228 (0%)	0	3/410 (0.7%)	3	0/212 (0%)	0	0/208 (0%)	0	0/30 (0%)	0	1/14 (7.1%)	1	1/20 (5%)	1	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0
Reproductive system and breast disorders
Vaginal discharge	0/393 (0%)	0	0/192 (0%)	0	0/196 (0%)	0	0/349 (0%)	0	1/179 (0.6%)	1	0/181 (0%)	0	0/22 (0%)	0	1/13 (7.7%)	2	0/14 (0%)	0	0/18 (0%)	0	0/13 (0%)	0	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	9/461 (2%)	9	4/226 (1.8%)	4	3/228 (1.3%)	3	2/410 (0.5%)	2	0/212 (0%)	0	1/208 (0.5%)	1	2/30 (6.7%)	3	0/14 (0%)	0	1/20 (5%)	1	0/25 (0%)	0	0/14 (0%)	0	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.