Trial record 1 of 1 for: EVOLVE-2

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02614196

Recruitment Status : Completed

First Posted : November 25, 2015

Results First Posted : January 7, 2019

Last Update Posted : June 17, 2020

Sponsor:

Information provided by (Responsible Party):

Eli Lilly and Company

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Migraine
Interventions	Drug: Galcanezumab Drug: Placebo
Enrollment	986

Participant Flow

Recruitment Details
Pre-assignment Details


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 su...	Participants received loading dose ...	Participants received 240mg galcane...	Participants received placebo by su...	Participants received loading dose ...	Participants received 240mg galcane...
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
Reason Not Completed
Adverse Event	8	5	9	0	0	0
Lack of Efficacy	6	1	1	0	0	0
Lost to Follow-up	10	7	1	0	0	0
Physician Decision	4	0	2	0	0	0
Pregnancy	1	2	0	0	0	0
Protocol Violation	5	2	1	0	1	0
Terminated by sponsor	1	0	0	0	0	0
Withdrawal by Subject	39	11	14	4	0	0
Did not receive study drug	2	2	3	0	0	0
Period Title: Post Treatment Follow-up Phase
Started	410 ^[1]	213 ^[1]	207 ^[1]	25 ^[1]	15 ^[1]	19 ^[1]
Completed	390	208	199	24	13	19
Not Completed	20	5	8	1	2	0
Reason Not Completed
Lost to Follow-up	8	3	3	0	1	0
Pregnancy	2	0	0	0	0	0
Protocol Violation	0	1	0	0	1	0
Withdrawal by Subject	10	1	5	1	0	0
[1] Participants who discontinued double blind phase had an option to enter post treatment phase

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 su...	Participants received loading dose ...	Participants received 240mg galcane...	Participants received placebo by su...	Participants received loading dose ...	Participants received 240mg galcane...	Total of all reporting groups
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 Number of Baseline Participants		461	231	223	30	15	19	979
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All randomized participants who received at least one dose of study drug for non-ME2 arms & All randomized participants for ME2 arms.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
		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 Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
	Female	393	197	191	22	13	14	830
	Male	68	34	32	8	2	5	149
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
	Hispanic or Latino	118	58	61	4	2	3	246
	Not Hispanic or Latino	318	162	151	21	10	12	674
	Unknown or Not Reported	25	11	11	5	3	4	59
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
	American Indian or Alaska Native	20	8	13	0	0	0	41
	Asian	50	28	24	30	15	19	166
	Native Hawaiian or Other Pacific Islander	0	0	2	0	0	0	2
	Black or African American	36	11	16	0	0	0	63
	White	325	166	152	0	0	0	643
	More than one race	30	18	16	0	0	0	64
	Unknown or Not Reported	0	0	0	0	0	0	0
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
Argentina		22	12	10	0	0	0	44
South Korea		34	17	17	14	7	9	98
Netherlands		24	11	11	0	0	0	46
United States		224	112	110	0	0	0	446
Czechia		39	19	19	0	0	0	77
Taiwan		12	7	5	16	8	10	58
Mexico		36	18	17	0	0	0	71
United Kingdom		8	4	3	0	0	0	15
Israel		11	5	5	0	0	0	21
Germany		37	19	19	0	0	0	75
Spain		14	7	7	0	0	0	28
Migraine Headache Days (MHD) per month ^[1] Mean (Standard Deviation) Unit of measure: Days per Month
	Number Analyzed	461 participants	231 participants	223 participants	30 participants	15 participants	19 participants	979 participants
		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)
		[1] Measure Description: Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred.

Outcome Measures

1.Primary Outcome


Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days
Description	Migraine Headache Day (M...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	450	226	220
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

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 (M...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	450	226	220
Mean (Standard Error) Unit of Measure: percentage of participants
≥50%	36 (1.7)	59.3 (2.4)	56.5 (2.5)
≥75%	17.8 (1.3)	33.5 (2.3)	34.3 (2.3)
100%	5.7 (0.7)	11.5 (1.4)	13.8 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥50%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.60
	Confidence Interval	(2-Sided) 95% 2.03 to 3.32
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥50%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95% 1.81 to 2.96
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥75%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95% 1.78 to 3.06
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥75%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95% 1.84 to 3.17
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	Reduction from Baseline ≥100%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95% 1.50 to 3.12
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	Reduction from Baseline ≥100%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.67
	Confidence Interval	(2-Sided) 95% 1.87 to 3.81
	Estimation Comments	[Not Specified]

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 t...
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 subcu...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	443	226	219
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

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 (M...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	450	226	220
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

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 patien...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	443	226	219
Least Squares Mean (Standard Error) Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.002
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.012
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

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 ...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	450	226	220
Least Squares Mean (Standard Error) Unit of Measure: 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, Galcanezumab120mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

7.Secondary Outcome


Title	Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score
Description	The MIDAS is a participa...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	409	216	215
Least Squares Mean (Standard Error) Unit of Measure: 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, Galcanezumab120mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

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	[Not Specified]

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 ...
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	443	222	214
Measure Type: Number Unit of Measure: percentage of participants
	0.45	8.56	5.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 120mg
	Comments	TE ADA Positive.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 240mg
	Comments	TE ADA Positive
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

9.Secondary Outcome


Title	Pharmacokinetics (PK): Serum Concentrations of Galcanezumab
Description	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 ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	194	193
Mean (Standard Deviation) Unit of Measure: 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).
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 su...	Participants received loading dose ...	Participants received 240mg galcane...
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.
Overall Number of Participants Analyzed	29	187	185
Mean (Standard Deviation) Unit of Measure: 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 subcu...		Participants received loading dose ...		Participants received 240mg galcane...		Participants didn't receive any int...		Participants didn't receive any int...		Participants didn't receive any int...		Participants received placebo subcu...		Participants received loading dose ...		Participants received 240mg galcane...		Participants didn't receive any int...		Participants didn't receive any int...		Participants didn't receive any int...
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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/461 (0.00%)		0/226 (0.00%)		0/228 (0.00%)		0/410 (0.00%)		0/212 (0.00%)		0/208 (0.00%)		0/30 (0.00%)		0/14 (0.00%)		0/20 (0.00%)		0/25 (0.00%)		0/14 (0.00%)		0/20 (0.00%)
Serious Adverse Events 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 (1.08%)		5/226 (2.21%)		7/228 (3.07%)		3/410 (0.73%)		1/212 (0.47%)		3/208 (1.44%)		1/30 (3.33%)		1/14 (7.14%)		0/20 (0.00%)		2/25 (8.00%)		0/14 (0.00%)		0/20 (0.00%)
Cardiac disorders
Acute myocardial infarction ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Endocrine disorders
Goitre ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Gastrointestinal disorders
Gastritis ^† 1	0/461 (0.00%)	0	1/226 (0.44%)	1	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Haemorrhoids ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Rectal polyp ^† 1	0/461 (0.00%)	0	1/226 (0.44%)	1	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
General disorders
Pyrexia ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Hepatobiliary disorders
Cholecystitis acute ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	1/25 (4.00%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0
Cholelithiasis ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Gallbladder polyp ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Infections and infestations
Appendicitis ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Influenza ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Pyelonephritis ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Urosepsis ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Injury, poisoning and procedural complications
Foot fracture ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Meniscus injury ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Rib fracture ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Road traffic accident ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	1/30 (3.33%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Patellofemoral pain syndrome ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix ^† 1 [1]	0/393 (0.00%)	0	1/192 (0.52%)	1	0/196 (0.00%)	0	0/349 (0.00%)	0	0/179 (0.00%)	0	0/181 (0.00%)	0	0/22 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0
Uterine leiomyoma ^† 1 [1]	0/393 (0.00%)	0	0/192 (0.00%)	0	0/196 (0.00%)	0	0/349 (0.00%)	0	1/179 (0.56%)	1	0/181 (0.00%)	0	0/22 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0
Nervous system disorders
Generalised tonic-clonic seizure ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Headache ^† 1	0/461 (0.00%)	0	1/226 (0.44%)	1	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Migraine ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	1/25 (4.00%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0
Transient ischaemic attack ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Psychiatric disorders
Disorientation ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Panic attack ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Post-traumatic stress disorder ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Suicide attempt ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Renal and urinary disorders
Bladder dysfunction ^† 1	0/461 (0.00%)	0	1/226 (0.44%)	1	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment [1] All randomized female participants.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (32.54%)		78/226 (34.51%)		87/228 (38.16%)		40/410 (9.76%)		16/212 (7.55%)		13/208 (6.25%)		10/30 (33.33%)		9/14 (64.29%)		9/20 (45.00%)		3/25 (12.00%)		6/14 (42.86%)		0/20 (0.00%)
Gastrointestinal disorders
Abdominal pain upper ^† 1	3/461 (0.65%)	3	4/226 (1.77%)	5	3/228 (1.32%)	3	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	2	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	1/25 (4.00%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0
Nausea ^† 1	15/461 (3.25%)	15	4/226 (1.77%)	4	3/228 (1.32%)	3	1/410 (0.24%)	1	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Vomiting ^† 1	4/461 (0.87%)	4	0/226 (0.00%)	0	2/228 (0.88%)	2	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
General disorders
Injection site pain ^† 1	39/461 (8.46%)	142	21/226 (9.29%)	100	20/228 (8.77%)	61	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Injection site reaction ^† 1	0/461 (0.00%)	0	7/226 (3.10%)	17	18/228 (7.89%)	25	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	3/20 (15.00%)	12	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Infections and infestations
Cystitis ^† 1	5/461 (1.08%)	5	2/226 (0.88%)	2	2/228 (0.88%)	2	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Hordeolum ^† 1	2/461 (0.43%)	2	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Influenza ^† 1	14/461 (3.04%)	16	3/226 (1.33%)	4	9/228 (3.95%)	9	5/410 (1.22%)	5	1/212 (0.47%)	1	1/208 (0.48%)	1	2/30 (6.67%)	2	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Nasopharyngitis ^† 1	41/461 (8.89%)	49	19/226 (8.41%)	23	16/228 (7.02%)	21	18/410 (4.39%)	19	5/212 (2.36%)	5	4/208 (1.92%)	5	1/30 (3.33%)	1	2/14 (14.29%)	2	2/20 (10.00%)	3	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Pharyngitis ^† 1	1/461 (0.22%)	1	0/226 (0.00%)	0	1/228 (0.44%)	1	2/410 (0.49%)	2	1/212 (0.47%)	1	1/208 (0.48%)	1	2/30 (6.67%)	2	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Rhinitis ^† 1	4/461 (0.87%)	4	2/226 (0.88%)	2	1/228 (0.44%)	2	0/410 (0.00%)	0	1/212 (0.47%)	1	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	1/25 (4.00%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0
Upper respiratory tract infection ^† 1	16/461 (3.47%)	19	13/226 (5.75%)	14	12/228 (5.26%)	12	3/410 (0.73%)	4	4/212 (1.89%)	5	2/208 (0.96%)	2	2/30 (6.67%)	2	3/14 (21.43%)	4	1/20 (5.00%)	1	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Vaginal infection ^† 1 [1]	0/393 (0.00%)	0	2/192 (1.04%)	2	1/196 (0.51%)	1	2/349 (0.57%)	2	0/179 (0.00%)	0	0/181 (0.00%)	0	0/22 (0.00%)	0	0/13 (0.00%)	0	1/14 (7.14%)	1	0/18 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0
Vulvovaginitis ^† 1 [1]	1/393 (0.25%)	1	0/192 (0.00%)	0	0/196 (0.00%)	0	0/349 (0.00%)	0	0/179 (0.00%)	0	0/181 (0.00%)	0	0/22 (0.00%)	0	0/13 (0.00%)	0	1/14 (7.14%)	1	0/18 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0
Injury, poisoning and procedural complications
Contusion ^† 1	3/461 (0.65%)	3	1/226 (0.44%)	1	2/228 (0.88%)	2	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	0/14 (0.00%)	0	2/20 (10.00%)	2	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Muscle strain ^† 1	1/461 (0.22%)	1	1/226 (0.44%)	1	1/228 (0.44%)	1	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	5/461 (1.08%)	5	4/226 (1.77%)	4	3/228 (1.32%)	3	1/410 (0.24%)	1	2/212 (0.94%)	2	0/208 (0.00%)	0	2/30 (6.67%)	2	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Arthritis ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	1/208 (0.48%)	1	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Back pain ^† 1	20/461 (4.34%)	24	2/226 (0.88%)	2	5/228 (2.19%)	5	4/410 (0.98%)	4	2/212 (0.94%)	2	1/208 (0.48%)	1	1/30 (3.33%)	1	2/14 (14.29%)	3	0/20 (0.00%)	0	1/25 (4.00%)	1	1/14 (7.14%)	1	0/20 (0.00%)	0
Foot deformity ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Intervertebral disc disorder ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	0/228 (0.00%)	0	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Nervous system disorders
Carpal tunnel syndrome ^† 1	0/461 (0.00%)	0	0/226 (0.00%)	0	1/228 (0.44%)	1	1/410 (0.24%)	1	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Dizziness ^† 1	10/461 (2.17%)	12	8/226 (3.54%)	10	7/228 (3.07%)	7	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	0/25 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0
Hypoaesthesia ^† 1	2/461 (0.43%)	2	0/226 (0.00%)	0	2/228 (0.88%)	2	0/410 (0.00%)	0	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	0/20 (0.00%)	0	1/25 (4.00%)	1	0/14 (0.00%)	0	0/20 (0.00%)	0
Psychiatric disorders
Insomnia ^† 1	8/461 (1.74%)	9	3/226 (1.33%)	3	0/228 (0.00%)	0	3/410 (0.73%)	3	0/212 (0.00%)	0	0/208 (0.00%)	0	0/30 (0.00%)	0	1/14 (7.14%)	1	1/20 (5.00%)	1	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
Reproductive system and breast disorders
Vaginal discharge ^† 1 [1]	0/393 (0.00%)	0	0/192 (0.00%)	0	0/196 (0.00%)	0	0/349 (0.00%)	0	1/179 (0.56%)	1	0/181 (0.00%)	0	0/22 (0.00%)	0	1/13 (7.69%)	2	0/14 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0	0/14 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	9/461 (1.95%)	9	4/226 (1.77%)	4	3/228 (1.32%)	3	2/410 (0.49%)	2	0/212 (0.00%)	0	1/208 (0.48%)	1	2/30 (6.67%)	3	0/14 (0.00%)	0	1/20 (5.00%)	1	0/25 (0.00%)	0	0/14 (0.00%)	0	0/20 (0.00%)	0
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment [1] All randomized female participants.

Limitations and 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.

Results Point of Contact

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Name/Title:	Chief Medical Officer
Organization:	Eli Lilly and Company
Phone:	800-545-5979
EMail:	ClinicalTrials.gov@lilly.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ament M, Day K, Stauffer VL, Skljarevski V, Rettiganti M, Pearlman E, Aurora SK. Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine. J Headache Pain. 2021 Feb 6;22(1):6. doi: 10.1186/s10194-021-01215-9.

Kuruppu DK, North JM, Kovacik AJ, Dong Y, Pearlman EM, Hutchinson SL. Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials. Adv Ther. 2021 Feb 5. doi: 10.1007/s12325-021-01632-x. [Epub ahead of print]

Dodick DW, Doty EG, Aurora SK, Ruff DD, Stauffer VL, Jedynak J, Dong Y, Pearlman EM. Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine. Cephalalgia. 2020 Nov 3:333102420966658. doi: 10.1177/0333102420966658. [Epub ahead of print]

Ailani J, Andrews JS, Rettiganti M, Nicholson RA. Impact of galcanezumab on total pain burden: findings from phase 3 randomized, double-blind, placebo-controlled studies in patients with episodic or chronic migraine (EVOLVE-1, EVOLVE-2, and REGAIN trials). J Headache Pain. 2020 Oct 17;21(1):123. doi: 10.1186/s10194-020-01190-7.

Stauffer VL, Turner I, Kemmer P, Kielbasa W, Day K, Port M, Quinlan T, Camporeale A. Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials. J Headache Pain. 2020 Jun 23;21(1):79. doi: 10.1186/s10194-020-01148-9.

Bangs ME, Kudrow D, Wang S, Oakes TM, Terwindt GM, Magis D, Yunes-Medina L, Stauffer VL. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020 Jan 17;20(1):25. doi: 10.1186/s12883-020-1609-7. Erratum in: BMC Neurol. 2020 Mar 13;20(1):90.

Kielbasa W, Quinlan T. Population Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, Following Subcutaneous Dosing to Healthy Individuals and Patients With Migraine. J Clin Pharmacol. 2020 Feb;60(2):229-239. doi: 10.1002/jcph.1511. Epub 2019 Sep 4.

Silberstein SD, Stauffer VL, Day KA, Lipsius S, Wilson MC. Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2). J Headache Pain. 2019 Jun 28;20(1):75. doi: 10.1186/s10194-019-1024-x. Erratum in: J Headache Pain. 2019 Dec 27;20(1):118.

Stauffer VL, Wang S, Voulgaropoulos M, Skljarevski V, Kovacik A, Aurora SK. Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials. Headache. 2019 Jun;59(6):834-847. doi: 10.1111/head.13508. Epub 2019 Apr 3.

Förderreuther S, Zhang Q, Stauffer VL, Aurora SK, Láinez MJA. Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. J Headache Pain. 2018 Dec 29;19(1):121. doi: 10.1186/s10194-018-0951-2.

Nichols R, Doty E, Sacco S, Ruff D, Pearlman E, Aurora SK. Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies. Headache. 2019 Feb;59(2):192-204. doi: 10.1111/head.13443. Epub 2018 Nov 21.

Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018 Jul;38(8):1442-1454. doi: 10.1177/0333102418779543. Epub 2018 May 31.

Layout table for additonal information

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT02614196
Other Study ID Numbers:	15768 I5Q-MC-CGAH ( Other Identifier: Eli Lilly and Company ) 2015-001882-17 ( EudraCT Number )
First Submitted:	November 23, 2015
First Posted:	November 25, 2015
Results First Submitted:	August 23, 2018
Results First Posted:	January 7, 2019
Last Update Posted:	June 17, 2020

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