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Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Episodic Migraine – the EVOLVE-2 Study

Summary
EudraCT number	2015-001882-17
Trial protocol	NL GB CZ DE ES
Global end of trial date	05 Oct 2018

Results information
Results version number	v1(current)
This version publication date	18 Oct 2019
First version publication date	18 Oct 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

I5Q-MC-CGAH

ISRCTN number

US NCT number

NCT02614196

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 15768

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon Fri 9 AM 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon Fri 9 AM 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

05 Oct 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Oct 2018

Was the trial ended prematurely?

Main objective of the trial

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.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Dec 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 44

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 98

Country: Number of subjects enrolled

Netherlands: 46

Country: Number of subjects enrolled

United States: 446

Country: Number of subjects enrolled

Czech Republic: 77

Country: Number of subjects enrolled

Taiwan: 58

Country: Number of subjects enrolled

Mexico: 71

Country: Number of subjects enrolled

United Kingdom: 15

Country: Number of subjects enrolled

Israel: 21

Country: Number of subjects enrolled

Germany: 75

Country: Number of subjects enrolled

Spain: 28

Worldwide total number of subjects

979

EEA total number of subjects

241

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

975

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Screening consisted of a full clinical assessment, including a comprehensive medical evaluation documenting medical history, and a physical and neurological examination.

Period 1 title

Double blind Treatment Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received placebo by subcutaneous injection once a month for 6 months.

Galcanezumab 120mg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

LY2951742

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.

Galcanezumab 240mg

Arm description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

LY2951742

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.

Placebo Maximum Extended Enrollment Cohort

Arm description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received placebo by subcutaneous injection once a month for 6 months.

Galcanezumab 120mg Maximum Extended Enrollment Cohort

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

LY2951742

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received loading dose of 240mg galcanezumab at 1st dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.

Galcanezumab 240mg Maximum Extended Enrollment Cohort

Arm description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

LY2951742

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.

Number of subjects in period 1	Placebo	Galcanezumab 120mg	Galcanezumab 240mg	Placebo Maximum Extended Enrollment Cohort	Galcanezumab 120mg Maximum Extended Enrollment Cohort	Galcanezumab 240mg Maximum Extended Enrollment Cohort
Started	461	231	223	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	74	28	28	4	1	0
Physician decision	4	-	2	-	-	-
Consent withdrawn by subject	39	11	14	4	-	-
Adverse event, non-fatal	8	5	9	-	-	-
Terminated by sponsor	1	-	-	-	-	-
Pregnancy	1	2	-	-	-	-
Lost to follow-up	10	7	1	-	-	-
Lack of efficacy	6	1	1	-	-	-
Protocol deviation	5	2	1	-	1	-

Period 2 title

Post Treatment Follow-up Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 120mg

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 240mg

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo Maximum Extended Enrollment Cohort

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 120mg Maximum Extended Enrollment Cohort

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 240mg Maximum Extended Enrollment Cohort

Arm description

Participants did not receive any intervention during post-treatment follow-up phase.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2 ^[1]	Placebo	Galcanezumab 120mg	Galcanezumab 240mg	Placebo Maximum Extended Enrollment Cohort	Galcanezumab 120mg Maximum Extended Enrollment Cohort	Galcanezumab 240mg Maximum Extended Enrollment Cohort
Started	387	203	195	25	14	19
Completed	390	208	199	24	13	19
Not completed	20	5	8	1	2	0
Consent withdrawn by subject	10	1	5	1	-	-
Pregnancy	2	-	-	-	-	-
Lost to follow-up	8	3	3	-	1	-
Protocol deviation	-	1	-	-	1	-
Joined	23	10	12	0	1	0
Double blind discontinued subjects	23	10	12	-	1	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants who discontinued double blind phase had an option to enter post treatment phase.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Galcanezumab 120mg

Reporting group description

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.

Reporting group title

Galcanezumab 240mg

Reporting group description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Placebo Maximum Extended Enrollment Cohort

Reporting group description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Galcanezumab 120mg Maximum Extended Enrollment Cohort

Reporting group description

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.

Reporting group title

Galcanezumab 240mg Maximum Extended Enrollment Cohort

Reporting group description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg	Placebo Maximum Extended Enrollment Cohort	Galcanezumab 120mg Maximum Extended Enrollment Cohort	Galcanezumab 240mg Maximum Extended Enrollment Cohort	Total
Number of subjects	461	231	223	30	15	19	979
Age categorical
Units: Subjects
In utero							0
Preterm newborn infants (gestational age < 37 wks)							0
Newborns (0-27 days)							0
Infants and toddlers (28 days-23 months)							0
Children (2-11 years)							0
Adolescents (12-17 years)							0
Adults (18-64 years)							0
From 65-84 years							0
85 years and over							0
Age Continuous
Units: years
arithmetic mean (standard deviation)	42.33 ( 11.30 )	40.91 ( 11.15 )	41.91 ( 10.77 )	45.37 ( 10.30 )	39.40 ( 11.58 )	42.58 ( 11.13 )	-
Gender categorical
Units: Subjects
Female	393	197	191	22	13	14	830
Male	68	34	32	8	2	5	149
Sex: Female, Male
Units: Subjects
Female	393	197	191	22	13	14	830
Male	68	34	32	8	2	5	149
Ethnicity (NIH/OMB)
Units: Subjects
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)
Units: Subjects
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
Units: Subjects
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
Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred.
Units: Days per Month
arithmetic mean (standard deviation)	9.19 ( 2.99 )	9.07 ( 2.87 )	9.06 ( 2.92 )	9.16 ( 2.98 )	9.06 ( 2.86 )	9.01 ( 2.90 )	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Galcanezumab 120mg

Reporting group description

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.

Reporting group title

Galcanezumab 240mg

Reporting group description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Placebo Maximum Extended Enrollment Cohort

Reporting group description

Participants received placebo by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Galcanezumab 120mg Maximum Extended Enrollment Cohort

Reporting group description

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.

Reporting group title

Galcanezumab 240mg Maximum Extended Enrollment Cohort

Reporting group description

Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months during double blind treatment phase.

Reporting group title

Placebo

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Reporting group title

Galcanezumab 120mg

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Reporting group title

Galcanezumab 240mg

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Reporting group title

Placebo Maximum Extended Enrollment Cohort

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Reporting group title

Galcanezumab 120mg Maximum Extended Enrollment Cohort

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Reporting group title

Galcanezumab 240mg Maximum Extended Enrollment Cohort

Reporting group description

Participants did not receive any intervention during post-treatment follow-up phase.

Primary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days

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End point title

Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days ^[1]

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

End point type

Primary

End point timeframe

Baseline, Month 1 through Month 6

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	450	226	220
Units: Days Per Month
least squares mean (standard error)	-2.28 ( 0.20 )	-4.29 ( 0.25 )	-4.18 ( 0.26 )

Statistical Analysis 1

Comparison groups

Galcanezumab 120mg v Placebo

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.02

Confidence interval

level

95%

sides

2-sided

lower limit

-2.55

upper limit

-1.48

Variability estimate

Standard error of the mean

Dispersion value

0.27

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.44

upper limit

-1.36

Variability estimate

Standard error of the mean

Dispersion value

0.27

Secondary: Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days

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End point title

Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days ^[2]

End point 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, and baseline as model terms. 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.

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 6

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	450	226	220
Units: percentage of participants
arithmetic mean (standard error)
≥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 description

Reduction from Baseline ≥50%

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.03

upper limit

3.32

Statistical Analysis 2

Statistical analysis description

Reduction from Baseline ≥50%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.81

upper limit

2.96

Statistical Analysis 3

Statistical analysis description

Reduction from Baseline ≥75%

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.34

Confidence interval

level

95%

sides

2-sided

lower limit

1.78

upper limit

3.06

Statistical Analysis 4

Statistical analysis description

Reduction from Baseline ≥75%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.42

Confidence interval

level

95%

sides

2-sided

lower limit

1.84

upper limit

3.17

Statistical Analysis 5

Statistical analysis description

Reduction from Baseline ≥100%

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.16

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

3.12

Statistical Analysis 6

Statistical analysis description

Reduction from Baseline ≥100%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.67

Confidence interval

level

95%

sides

2-sided

lower limit

1.87

upper limit

3.81

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain

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End point title

Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain ^[3]

End point 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 and, 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.

End point type

Secondary

End point timeframe

Baseline, Month 4 through Month 6 APD: All randomized participants who received at least one dose of study drug and had baseline & at least one post baseline value.

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	443	226	219
Units: units on a scale
least squares mean (standard error)	19.65 ( 0.92 )	28.47 ( 1.15 )	27.04 ( 1.17 )

Statistical Analysis 1

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

669

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

8.82

Confidence interval

level

95%

sides

2-sided

lower limit

6.33

upper limit

11.31

Variability estimate

Standard error of the mean

Dispersion value

1.27

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

662

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

7.39

Confidence interval

level

95%

sides

2-sided

lower limit

4.88

upper limit

9.9

Variability estimate

Standard error of the mean

Dispersion value

1.28

Secondary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache

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End point title

Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache ^[4]

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

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 6

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	450	226	220
Units: Medication Used Days
least squares mean (standard error)	-1.85 ( 0.18 )	-3.67 ( 0.22 )	-3.63 ( 0.23 )

Statistical Analysis 1

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.82

Confidence interval

level

95%

sides

2-sided

lower limit

-2.29

upper limit

-1.36

Variability estimate

Standard error of the mean

Dispersion value

0.24

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.78

Confidence interval

level

95%

sides

2-sided

lower limit

-2.25

upper limit

-1.31

Variability estimate

Standard error of the mean

Dispersion value

0.24

Secondary: Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating

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End point title

Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating ^[5]

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

End point type

Secondary

End point timeframe

Baseline, Month 4 through Month 6

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	443	226	219
Units: units on a scale
least squares mean (standard error)	-0.94 ( 0.07 )	-1.22 ( 0.08 )	-1.17 ( 0.08 )

Statistical Analysis 1

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

669

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.09

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

662

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Overall Mean Change from Baseline in Headache Hours

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End point title

Overall Mean Change from Baseline in Headache Hours ^[6]

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

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 6

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	450	226	220
Units: Headache Hours per Month
least squares mean (standard error)	-10.89 ( 1.92 )	-26.07 ( 2.41 )	-24.44 ( 2.44 )

Statistical Analysis 1

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-15.19

Confidence interval

level

95%

sides

2-sided

lower limit

-20.27

upper limit

-10.11

Variability estimate

Standard error of the mean

Dispersion value

2.59

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-13.56

Confidence interval

level

95%

sides

2-sided

lower limit

-18.67

upper limit

-8.44

Variability estimate

Standard error of the mean

Dispersion value

2.6

Secondary: Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score

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End point title

Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score ^[7]

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

End point type

Secondary

End point timeframe

Baseline, Month 6

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	409	216	215
Units: units on a scale
least squares mean (standard error)	-12.02 ( 1.27 )	-21.17 ( 1.58 )	-20.24 ( 1.62 )

Statistical Analysis 1

Comparison groups

Galcanezumab 120mg v Placebo

Number of subjects included in analysis

625

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-9.15

Confidence interval

level

95%

sides

2-sided

lower limit

-12.61

upper limit

-5.69

Variability estimate

Standard error of the mean

Dispersion value

1.76

Statistical Analysis 2

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

624

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-8.22

Confidence interval

level

95%

sides

2-sided

lower limit

-11.71

upper limit

-4.72

Variability estimate

Standard error of the mean

Dispersion value

1.78

Secondary: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab

Top of page

End point title

Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab ^[8]

End point 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. APD: 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.

End point type

Secondary

End point timeframe

Month 1 through Month 6

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	443	222	214
Units: percentage of participants
number (not applicable)	0.45	8.56	5.14

Statistical Analysis 1

Statistical analysis description

TE ADA Positive.

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

665

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 2

Statistical analysis description

TE ADA Positive

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

657

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 3

Statistical analysis description

Neutralizing Antibodies

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

665

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 4

Statistical analysis description

Neutralizing Antibodies

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

657

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Secondary: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab

Top of page

End point title

Pharmacokinetics (PK): Serum Concentrations of Galcanezumab ^[9]

End point description

APD: All randomized participants who received at least one dose of study drug and had measurable serum concentrations.

End point type

Secondary

End point timeframe

Month 6

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	194	193
Units: Nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)	17400 ( 8820 )	32200 ( 12600 )

No statistical analyses for this end point

Secondary: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Top of page

End point title

Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) ^[10]

End point description

APD: All randomized participants who had received at least one dose of study drug and had measurable plasma concentration.

End point type

Secondary

End point timeframe

Month 6

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per Protocol, Statistical Analysis was not planned.

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	29	187	185
Units: ng/mL
arithmetic mean (standard deviation)	0.541 ( 1.11 )	3.93 ( 1.83 )	4.98 ( 1.60 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Entire Study

Adverse event reporting additional description

5 participants in Gal - 120mg treatment, 1 participant in Gal - 120mg post- treatment , & 1 participant in Gal - 120 mg treatment ME2 & 1 participant in Gal - 120mg post-treatment ME2 arms who discontinued after receiving loading dose of 240mg, these participants were included in Gal - 240mg treatment and post treatment equivalent ME2 arms.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo - Treatment Phase

Reporting group description

Reporting group title

Galcanezumab 120mg - Treatment Phase

Reporting group description

Reporting group title

Galcanezumab 240mg - Treatment Phase

Reporting group description

Reporting group title

Placebo - Post-treatment Phase

Reporting group description

Reporting group title

Galcanezumab 120mg - Post-treatment Phase

Reporting group description

Reporting group title

Galcanezumab 240mg - Post-treatment Phase

Reporting group description

Reporting group title

Galcanezumab 120mg ME2 - Treatment Phase

Reporting group description

Reporting group title

Placebo ME2 - Treatment Phase

Reporting group description

Reporting group title

Galcanezumab 240mg ME2 - Treatment Phase

Reporting group description

Reporting group title

Placebo ME2 - Post-treatment Phase

Reporting group description

Reporting group title

Galcanezumab 120mg ME2 - Post-treatment Phase

Reporting group description

Reporting group title

Galcanezumab 240mg ME2 - Post-treatment Phase

Reporting group description

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

Galcanezumab 120mg ME2 - Treatment Phase

Placebo ME2 - Treatment Phase

Galcanezumab 240mg ME2 - Treatment Phase

Placebo ME2 - Post-treatment Phase

Galcanezumab 120mg ME2 - Post-treatment Phase

Galcanezumab 240mg ME2 - Post-treatment Phase

Total subjects affected by serious adverse events

subjects affected / exposed

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 / 14 (7.14%)

1 / 30 (3.33%)

0 / 20 (0.00%)

2 / 25 (8.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

adenocarcinoma of the cervix

alternative dictionary used: MedDRA 20.1

subjects affected / exposed ^[1]

0 / 393 (0.00%)

1 / 192 (0.52%)

0 / 196 (0.00%)

0 / 349 (0.00%)

0 / 179 (0.00%)

0 / 181 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 14 (0.00%)

0 / 18 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

uterine leiomyoma

alternative dictionary used: MedDRA 20.1

subjects affected / exposed ^[2]

0 / 393 (0.00%)

0 / 192 (0.00%)

0 / 196 (0.00%)

0 / 349 (0.00%)

1 / 179 (0.56%)

0 / 181 (0.00%)

0 / 13 (0.00%)

0 / 22 (0.00%)

0 / 14 (0.00%)

0 / 18 (0.00%)

0 / 13 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

pyrexia

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

nasal septum deviation

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

1 / 14 (7.14%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

disorientation

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

panic attack

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

1 / 208 (0.48%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

post-traumatic stress disorder

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

1 / 208 (0.48%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

suicide attempt

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

foot fracture

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

meniscus injury

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rib fracture

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

generalised tonic-clonic seizure

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

headache

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

1 / 226 (0.44%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

migraine

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

1 / 25 (4.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

transient ischaemic attack

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

gastritis

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

1 / 226 (0.44%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemorrhoids

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

rectal polyp

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

1 / 226 (0.44%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholecystitis acute

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

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 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

1 / 25 (4.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cholelithiasis

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gallbladder polyp

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

1 / 461 (0.22%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

bladder dysfunction

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

1 / 226 (0.44%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

goitre

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

1 / 410 (0.24%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

arthralgia

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

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 / 14 (0.00%)

1 / 30 (3.33%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

patellofemoral pain syndrome

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

0 / 410 (0.00%)

0 / 212 (0.00%)

1 / 208 (0.48%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

appendicitis

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

1 / 410 (0.24%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

influenza

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

1 / 228 (0.44%)

0 / 410 (0.00%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pyelonephritis

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

1 / 410 (0.24%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urosepsis

alternative dictionary used: MedDRA 20.1

subjects affected / exposed

0 / 461 (0.00%)

0 / 226 (0.00%)

0 / 228 (0.00%)

1 / 410 (0.24%)

0 / 212 (0.00%)

0 / 208 (0.00%)

0 / 14 (0.00%)

0 / 30 (0.00%)

0 / 20 (0.00%)

0 / 25 (0.00%)

0 / 14 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender based AE occurred only in female participants.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender based AE occurred only in female participants.

Frequency threshold for reporting non-serious adverse events: 5%

Non-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	Galcanezumab 120mg ME2 - Treatment Phase	Placebo ME2 - Treatment Phase	Galcanezumab 240mg ME2 - Treatment Phase	Placebo ME2 - Post-treatment Phase	Galcanezumab 120mg ME2 - Post-treatment Phase	Galcanezumab 240mg ME2 - Post-treatment Phase
Total subjects affected by non serious adverse events
subjects affected / exposed	150 / 461 (32.54%)	78 / 226 (34.51%)	87 / 228 (38.16%)	40 / 410 (9.76%)	16 / 212 (7.55%)	13 / 208 (6.25%)	9 / 14 (64.29%)	10 / 30 (33.33%)	9 / 20 (45.00%)	3 / 25 (12.00%)	6 / 14 (42.86%)	0 / 20 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
skin papilloma
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 461 (0.00%)	0 / 226 (0.00%)	0 / 228 (0.00%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
Injury, poisoning and procedural complications
contusion
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 461 (0.65%)	1 / 226 (0.44%)	2 / 228 (0.88%)	0 / 410 (0.00%)	0 / 212 (0.00%)	1 / 208 (0.48%)	0 / 14 (0.00%)	0 / 30 (0.00%)	2 / 20 (10.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	1	2	0	0	1	0	0	2	0	0	0
muscle strain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 461 (0.22%)	1 / 226 (0.44%)	1 / 228 (0.44%)	1 / 410 (0.24%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	1	1	0	0	1	0	0	0	0	0
Nervous system disorders
carpal tunnel syndrome
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 461 (0.00%)	0 / 226 (0.00%)	1 / 228 (0.44%)	1 / 410 (0.24%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	1	0	0	1	0	0	0	0	0
dizziness
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	10 / 461 (2.17%)	8 / 226 (3.54%)	7 / 228 (3.07%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	12	10	7	0	0	0	1	0	0	0	1	0
hypoaesthesia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 461 (0.43%)	0 / 226 (0.00%)	2 / 228 (0.88%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	2	0	0	0	1	0	0	1	0	0
General disorders and administration site conditions
injection site pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	39 / 461 (8.46%)	21 / 226 (9.29%)	20 / 228 (8.77%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	142	100	61	0	0	0	0	0	0	0	0	0
injection site reaction
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 461 (0.00%)	7 / 226 (3.10%)	18 / 228 (7.89%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	3 / 20 (15.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	17	25	0	0	0	1	0	12	0	0	0
Gastrointestinal disorders
abdominal pain upper
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 461 (0.65%)	4 / 226 (1.77%)	3 / 228 (1.32%)	0 / 410 (0.00%)	0 / 212 (0.00%)	1 / 208 (0.48%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	5	3	0	0	2	1	0	0	1	0	0
nausea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	15 / 461 (3.25%)	4 / 226 (1.77%)	3 / 228 (1.32%)	1 / 410 (0.24%)	0 / 212 (0.00%)	1 / 208 (0.48%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	15	4	3	1	0	1	1	0	0	0	1	0
vomiting
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	4 / 461 (0.87%)	0 / 226 (0.00%)	2 / 228 (0.88%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	4	0	2	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	9 / 461 (1.95%)	4 / 226 (1.77%)	3 / 228 (1.32%)	2 / 410 (0.49%)	0 / 212 (0.00%)	1 / 208 (0.48%)	0 / 14 (0.00%)	2 / 30 (6.67%)	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	9	4	3	2	0	1	0	3	1	0	0	0
vaginal discharge
alternative dictionary used: MedDRA 20.1
subjects affected / exposed ^[3]	0 / 393 (0.00%)	0 / 192 (0.00%)	0 / 196 (0.00%)	0 / 349 (0.00%)	1 / 179 (0.56%)	0 / 181 (0.00%)	1 / 13 (7.69%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0	0	0	0
Psychiatric disorders
insomnia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	8 / 461 (1.74%)	3 / 226 (1.33%)	0 / 228 (0.00%)	3 / 410 (0.73%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	9	3	0	3	0	0	1	0	1	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	5 / 461 (1.08%)	4 / 226 (1.77%)	3 / 228 (1.32%)	1 / 410 (0.24%)	2 / 212 (0.94%)	0 / 208 (0.00%)	1 / 14 (7.14%)	2 / 30 (6.67%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	5	4	3	1	2	0	1	2	0	0	1	0
arthritis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 461 (0.00%)	0 / 226 (0.00%)	0 / 228 (0.00%)	0 / 410 (0.00%)	0 / 212 (0.00%)	1 / 208 (0.48%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0
back pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	20 / 461 (4.34%)	2 / 226 (0.88%)	5 / 228 (2.19%)	4 / 410 (0.98%)	2 / 212 (0.94%)	1 / 208 (0.48%)	2 / 14 (14.29%)	1 / 30 (3.33%)	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	24	2	5	4	2	1	3	1	0	1	1	0
foot deformity
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	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 / 14 (0.00%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
intervertebral disc disorder
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	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 / 14 (0.00%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Infections and infestations
cystitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	5 / 461 (1.08%)	2 / 226 (0.88%)	2 / 228 (0.88%)	1 / 410 (0.24%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	5	2	2	1	0	0	1	0	0	0	0	0
hordeolum
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 461 (0.43%)	0 / 226 (0.00%)	0 / 228 (0.00%)	0 / 410 (0.00%)	0 / 212 (0.00%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0	0	1	0	0	0	0	0
influenza
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	14 / 461 (3.04%)	3 / 226 (1.33%)	9 / 228 (3.95%)	5 / 410 (1.22%)	1 / 212 (0.47%)	1 / 208 (0.48%)	0 / 14 (0.00%)	2 / 30 (6.67%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	16	4	9	5	1	1	0	2	0	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	41 / 461 (8.89%)	19 / 226 (8.41%)	16 / 228 (7.02%)	18 / 410 (4.39%)	5 / 212 (2.36%)	4 / 208 (1.92%)	2 / 14 (14.29%)	1 / 30 (3.33%)	2 / 20 (10.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	49	23	21	19	5	5	2	1	3	0	1	0
pharyngitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 461 (0.22%)	0 / 226 (0.00%)	1 / 228 (0.44%)	2 / 410 (0.49%)	1 / 212 (0.47%)	1 / 208 (0.48%)	0 / 14 (0.00%)	2 / 30 (6.67%)	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	0	1	2	1	1	0	2	0	0	0	0
rhinitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	4 / 461 (0.87%)	2 / 226 (0.88%)	1 / 228 (0.44%)	0 / 410 (0.00%)	1 / 212 (0.47%)	0 / 208 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 14 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	2	2	0	1	0	1	0	0	1	0	0
upper respiratory tract infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	16 / 461 (3.47%)	13 / 226 (5.75%)	12 / 228 (5.26%)	3 / 410 (0.73%)	4 / 212 (1.89%)	2 / 208 (0.96%)	3 / 14 (21.43%)	2 / 30 (6.67%)	1 / 20 (5.00%)	0 / 25 (0.00%)	1 / 14 (7.14%)	0 / 20 (0.00%)
occurrences all number	19	14	12	4	5	2	4	2	1	0	1	0
vaginal infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed ^[4]	0 / 393 (0.00%)	2 / 192 (1.04%)	1 / 196 (0.51%)	2 / 349 (0.57%)	0 / 179 (0.00%)	0 / 181 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	2	1	2	0	0	0	0	1	0	0	0
vulvovaginitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed ^[5]	1 / 393 (0.25%)	0 / 192 (0.00%)	0 / 196 (0.00%)	0 / 349 (0.00%)	0 / 179 (0.00%)	0 / 181 (0.00%)	0 / 13 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 18 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0	0

Notes
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender based AE occurred only in female participants.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender based AE occurred only in female participants.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Gender based AE occurred only in female participants.

More information

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Were there any global substantial amendments to the protocol? Yes

22 Jan 2016

Exclusion criteria updated to excluded patients with a prior lifetime history of stroke to provide additional safeguards for patients who may be at risk for stroke. Added text to indicate that neurological examinations will be conducted to assess for possible cerebrovascular events, along with instructions for appropriate follow-up. Reworded the procedures associated with emergency unblinding. Modified treatment discontinuation criteria. Added clarification on the statistical model to be used for subgroup analyses. Updated the Schedule of Activities and footnotes to reflect added neurological examinations.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Episodic Migraine – the EVOLVE-2 Study

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days

Primary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days

Secondary: Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days

Secondary: Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain

Secondary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache

Secondary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache

Secondary: Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating

Secondary: Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score

Secondary: Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score

Secondary: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab

Secondary: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab

Secondary: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab

Secondary: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab

Secondary: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Secondary: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Episodic Migraine – the EVOLVE-2 Study

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days

Primary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days

Secondary: Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days

Secondary: Mean Percentage of Participants with Reduction from Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain

Secondary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache

Secondary: Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache

Secondary: Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating

Secondary: Mean Change from Baseline in Patient Global Impression of Severity (PGI-S) Rating

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score

Secondary: Mean Change from Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score

Secondary: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab

Secondary: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab

Secondary: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab

Secondary: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab

Secondary: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Secondary: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Episodic Migraine – the EVOLVE-2 Study