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Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Chronic Migraine - the REGAIN Study.

Summary
EudraCT number	2015-001883-21
Trial protocol	NL GB CZ DE IT
Global end of trial date	14 Jul 2021

Results information
Results version number	v1(current)
This version publication date	11 May 2022
First version publication date	11 May 2022
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-CGAI

ISRCTN number

US NCT number

NCT02614261

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 15769

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

14 Jul 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Jul 2021

Was the trial ended prematurely?

Main objective of the trial

The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with chronic 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

30 Nov 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 629

Country: Number of subjects enrolled

Argentina: 82

Country: Number of subjects enrolled

Canada: 15

Country: Number of subjects enrolled

Czechia: 45

Country: Number of subjects enrolled

Germany: 54

Country: Number of subjects enrolled

Spain: 50

Country: Number of subjects enrolled

United Kingdom: 31

Country: Number of subjects enrolled

Israel: 40

Country: Number of subjects enrolled

Italy: 56

Country: Number of subjects enrolled

Mexico: 24

Country: Number of subjects enrolled

Netherlands: 43

Country: Number of subjects enrolled

Taiwan: 48

Worldwide total number of subjects

1117

EEA total number of subjects

248

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)

1104

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Main study: This randomised part of study was conducted in 3 phases: a 3-month double-blind treatment phase followed by an optional 9-month open-label extension phase and a 4-month follow-up phase. Israel addendum: Participants in Israel who completed all phases in main study, benefited from galcanezumab and (cont'd)..

Screening details

..(cont'd) did not have alternative treatment options available were provided continued-access to treatment where safety was monitored.

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

Placebo

Arm description

Double-blind treatment phase: Participants received placebo once a month by subcutaneous (SC) injection for 3 months.

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

Placebo once a month by subcutaneous (SC) injection for 3 months.

Galcanezumab 120mg

Arm description

Double-blind treatment phase: Participants received loading dose of 240 mg of galcanezumab at first dosing visit followed 120 mg galcanezumab once a month by subcutaneous injection for 2 months.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

240 milligrams (mg) of galcanezumab at first dosing visit followed 120 mg galcanezumab once a month by subcutaneous injection for 2 months.

Galcanezumab 240mg

Arm description

Double-blind treatment phase: Participants received 240 mg of galcanezumab once a month by subcutaneous injection for 3 months.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

240 mg of galcanezumab once a month by subcutaneous injection for 3 months.

Number of subjects in period 1	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Started	559	279	279
Received at least one dose of study drug	558	278	277
Completed	509	262	266
Not completed	50	17	13
Physician decision	2	1	1
Consent withdrawn by subject	20	5	7
Screen Failure	-	1	2
Adverse event, non-fatal	7	3	2
Pregnancy	2	2	-
Lost to follow-up	9	4	1
Lack of efficacy	4	-	-
Protocol deviation	6	1	-

Period 2 title

Open-Label Extension Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Open-label extension phase: After completion of double-blind phase, participants had an option to enter open-label extension phase where they receive 240 milligram (mg) galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Arm type

Placebo

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

240 mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Galcanezumab 120mg

Arm description

Open-label extension phase: After completion of double-blind phase, participants had an option to enter open-label extension phase where they received 240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Galcanezumab 240mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Number of subjects in period 2	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Started	501	259	262
Completed	413	204	208
Not completed	88	55	54
Physician decision	2	-	-
Consent withdrawn by subject	30	18	18
Adverse event, non-fatal	23	12	11
Pregnancy	1	2	1
Lost to follow-up	15	7	9
Lack of efficacy	14	12	14
Protocol deviation	3	4	1

Period 3 title

Follow-up Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Placebo

Arm description

Follow-up phase: After completion or discontinuation from double-blind or open-label extension phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 120mg

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Galcanezumab 240mg

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 3	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Started	453	228	231
Entered From Double-blind Phase	15 ^[1]	5 ^[2]	3 ^[3]
Entered From Open-label Extension Phase	438	223	228
Completed	421	217	217
Not completed	32	11	14
Physician decision	5	1	-
Consent withdrawn by subject	12	4	11
Adverse event, non-fatal	2	-	1
Pregnancy	-	1	-
Lost to follow-up	12	5	2
Protocol deviation	1	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Breakdown of participants who entered follow-up phase from Double-blind phase, Open-label Extension Phase.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Breakdown of participants who entered follow-up phase from Double-blind phase, Open-label Extension Phase.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Breakdown of participants who entered follow-up phase from Double-blind phase, Open-label Extension Phase.

Period 4 title

Israel Addendum

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Israel Addendum

Arm description

Eligible participants from main study were enrolled in Israel addendum. Participants received 120mg or 240mg galcanezumab SC once a month, at the discretion of the investigator, for up to 3 years or until Israel's Ministry of Health's conditions for continued access cease to be met, whichever occurs first.

Arm type

Experimental

Investigational medicinal product name

Galcanezumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

120mg or 240mg galcanezumab SC once a month, at the discretion of the investigator, for up to 3 years or until Israel's Ministry of Health's conditions for continued access cease to be met, whichever occurs first.

Number of subjects in period 4	Israel Addendum
Started	29
Completed	25
Not completed	4
Consent withdrawn by subject	4

Baseline characteristics

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Reporting group title

Double-Blind Treatment Phase

Reporting group description

Reporting group values	Double-Blind Treatment Phase	Total
Number of subjects	1117	1117
Age categorical
Units: Subjects
Adolescents (12-17 years)	4	4
Adults (18-64 years)	1104	1104
From 65-84 years	9	9
Age continuous
Units: years
arithmetic mean (standard deviation)	40.98 ( 12.11 )	-
Gender categorical
Units: Subjects
Female	950	950
Male	167	167
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	256	256
Not Hispanic or Latino	792	792
Unknown or Not Reported	69	69
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	6	6
Asian	54	54
Native Hawaiian or Other Pacific Islander	1	1
Black or African American	72	72
White	882	882
More than one race	101	101
Unknown or Not Reported	1	1

End points

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Reporting group title

Placebo

Reporting group description

Double-blind treatment phase: Participants received placebo once a month by subcutaneous (SC) injection for 3 months.

Reporting group title

Galcanezumab 120mg

Reporting group description

Double-blind treatment phase: Participants received loading dose of 240 mg of galcanezumab at first dosing visit followed 120 mg galcanezumab once a month by subcutaneous injection for 2 months.

Reporting group title

Galcanezumab 240mg

Reporting group description

Double-blind treatment phase: Participants received 240 mg of galcanezumab once a month by subcutaneous injection for 3 months.

Reporting group title

Placebo

Reporting group description

Reporting group title

Galcanezumab 120mg

Reporting group description

Reporting group title

Galcanezumab 240mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Galcanezumab 120mg

Reporting group description

Reporting group title

Galcanezumab 240mg

Reporting group description

Reporting group title

Israel Addendum

Reporting group description

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

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End point title

Overall Mean Change from Baseline in the Number of Monthly Migraine Headache Days (MHD)

End point description

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

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	538	273	274
Units: Migraine Headache Days per Month
least squares mean (standard error)	-2.74 ( 0.36 )	-4.83 ( 0.44 )	-4.62 ( 0.43 )

Statistical analysis 1

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.09

Confidence interval

level

95%

sides

2-sided

lower limit

-2.92

upper limit

-1.26

Variability estimate

Standard error of the mean

Dispersion value

0.42

Statistical analysis 1

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

812

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-2.71

upper limit

-1.05

Variability estimate

Standard error of the mean

Dispersion value

0.42

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

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End point title

Number of Participants with Reduction from Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days

End point description

MHD: A calendar day on which a migraine headache or probable migraine headache occurred. APD: All randomized participants who received at least one dose of study drug and had baseline and month 3 measurement.

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	498	256	262
Units: participants
≥50%	123	90	97
≥75%	44	34	40
≥100%	8	4	8

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥50%,

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

754

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.004

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

1.623

Confidence interval

level

95%

sides

2-sided

lower limit

1.167

upper limit

2.256

Notes
[1] - Reduction from Baseline ≥50%,

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥50%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

760

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.001

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

1.788

Confidence interval

level

95%

sides

2-sided

lower limit

1.291

upper limit

2.474

Notes
[2] - Reduction from Baseline ≥50%

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥75%

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

754

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.102

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

1.498

Confidence interval

level

95%

sides

2-sided

lower limit

0.923

upper limit

2.43

Notes
[3] - Reduction from Baseline ≥75%

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥75%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

760

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.011

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

1.819

Confidence interval

level

95%

sides

2-sided

lower limit

1.146

upper limit

2.888

Notes
[4] - Reduction from Baseline ≥75%

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥100%

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

754

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.729

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

0.761

Confidence interval

level

95%

sides

2-sided

lower limit

0.163

upper limit

3.563

Notes
[5] - Reduction from Baseline ≥100%

Statistical analysis 2

Statistical analysis description

Reduction from Baseline ≥100%

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

760

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.276

Method

CPRMM

Parameter type

Odds ratio (OR)

Point estimate

1.897

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

5.998

Notes
[6] - Reduction from Baseline ≥100%

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

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End point title

Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role-function Restrictive Domain

End point description

MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. 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. APD: All randomized participants who received at least one dose of study drug and had baseline and month 3 measurement.

End point type

Secondary

End point timeframe

Baseline, Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	494	252	253
Units: units on a scale
least squares mean (standard error)	16.76 ( 1.18 )	21.81 ( 1.41 )	23.05 ( 1.63 )

Statistical analysis 3

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

746

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

5.06

Confidence interval

level

95%

sides

2-sided

lower limit

2.12

upper limit

7.99

Variability estimate

Standard error of the mean

Dispersion value

1.5

Statistical analysis 3

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

747

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

6.29

Confidence interval

level

95%

sides

2-sided

lower limit

3.03

upper limit

9.55

Variability estimate

Standard error of the mean

Dispersion value

1.66

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

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 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, 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 measurement.

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	538	273	274
Units: Days Per Month
least squares mean (standard error)	-2.23 ( 0.33 )	-4.74 ( 0.40 )	-4.25 ( 0.40 )

Statistical analysis 4

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.51

Confidence interval

level

95%

sides

2-sided

lower limit

-3.27

upper limit

-1.76

Variability estimate

Standard error of the mean

Dispersion value

0.38

Statistical analysis 4

Comparison groups

Galcanezumab 240mg v Placebo

Number of subjects included in analysis

812

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-2.01

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

-1.26

Variability estimate

Standard error of the mean

Dispersion value

0.38

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

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End point title

Mean Change from Baseline in the Patient Global Impression of Severity (PGI-S) Score

End point description

PGI-S scale is a participant-rated instrument that measures participants 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"). LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, 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 month 3 measurement.

End point type

Secondary

End point timeframe

Baseline, Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	494	252	253
Units: units on a scale
least squares mean (standard error)	-0.62 ( 0.08 )	-0.76 ( 0.10 )	-0.91 ( 0.10 )

Statistical analysis 5

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

746

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.181

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.1

Statistical analysis 5

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

747

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.1

Secondary: Overall Mean Change from Baseline in Headache Hours

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End point title

Overall Mean Change from Baseline in Headache Hours

End point description

Overall mean is derived from the average of months 1 to 3 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, month, 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 & at least one post baseline measurement.

End point type

Secondary

End point timeframe

Baseline, Month 1 through Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	538	273	274
Units: Headache Hours per Month
least squares mean (standard error)	-13.44 ( 3.91 )	-36.15 ( 4.74 )	-31.53 ( 4.70 )

Statistical analysis 6

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

811

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-22.71

Confidence interval

level

95%

sides

2-sided

lower limit

-31.74

upper limit

-13.69

Variability estimate

Standard error of the mean

Dispersion value

4.6

Statistical analysis 6

Comparison groups

Galcanezumab 240mg v Placebo

Number of subjects included in analysis

812

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LSMean Difference

Point estimate

-18.09

Confidence interval

level

95%

sides

2-sided

lower limit

-27.09

upper limit

-9.09

Variability estimate

Standard error of the mean

Dispersion value

4.58

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

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End point title

Mean Change from Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score

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 Analysis of covariance (ANCOVA) model with last observation carried forward (LOCF) with treatment, pooled country, baseline medication overuse, concurrent prophylaxis use, and baseline value 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 measurement.

End point type

Secondary

End point timeframe

Baseline, Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	504	254	258
Units: units on a scale
least squares mean (standard error)	-11.53 ( 3.38 )	-20.27 ( 4.07 )	-17.02 ( 4.05 )

Statistical analysis 7

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

758

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.025

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-8.74

Confidence interval

level

95%

sides

2-sided

lower limit

-16.39

upper limit

-1.08

Variability estimate

Standard error of the mean

Dispersion value

3.9

Statistical analysis 7

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

762

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.157

Method

ANCOVA

Parameter type

LSMean Difference

Point estimate

-5.49

Confidence interval

level

95%

sides

2-sided

lower limit

-13.1

upper limit

2.12

Variability estimate

Standard error of the mean

Dispersion value

3.88

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

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End point title

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

End point description

A Treatment Emergent Anti-Drug Antibodies (TE ADA) evaluable participant is considered to be TE ADA+ if the participant 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 >= 20. APD: All randomized participants who received at least one dose of study drug and had at 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 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	535	264	272
Units: participants	8	7	7

Statistical analysis 8

Comparison groups

Placebo v Galcanezumab 120mg

Number of subjects included in analysis

799

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263

Method

Cochran-Mantel-Haenszel

Confidence interval

Statistical analysis 8

Comparison groups

Placebo v Galcanezumab 240mg

Number of subjects included in analysis

807

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.29

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab

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End point title

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab ^[7]

End point description

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab. APD: Zero participants analyzed. AUC data was not collected as AUC was not pre-specified in protocol.

End point type

Secondary

End point timeframe

Baseline through Month 3

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: PK outcomes only for active drug - Galcanezumab.

End point values	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	0 ^[8]	0 ^[9]
Units: nanograms*hours per milliliter
geometric mean (geometric coefficient of variation)	( )	( )

Notes
[8] - Zero participants analyzed. AUC data was not collected as AUC was not pre-specified in protocol.
[9] - Zero participants analyzed. AUC data was not collected as AUC was not pre-specified in protocol.

No statistical analyses for this end point

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

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End point title

Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

End point description

Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP). APD: All randomized participants who received at least one dose of study drug and had measurable plasma concentrations.

End point type

Secondary

End point timeframe

Month 3

End point values	Placebo	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	30	247	253
Units: Nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)	0.529 ( 0.612 )	4.02 ( 1.70 )	4.85 ( 1.76 )

No statistical analyses for this end point

Secondary: Serum concentrations of Galcanezumab

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End point title

Serum concentrations of Galcanezumab ^[10]

End point description

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

End point type

Secondary

End point timeframe

Month 3

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: PK outcomes only for active drug - Galcanezumab.

End point values	Galcanezumab 120mg	Galcanezumab 240mg
Number of subjects analysed	248	254
Units: Nanogram per milliliter (ng/mL)
arithmetic mean (standard deviation)	16900 ( 7140 )	29000 ( 11300 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline to 16 months for main study plus additional 3 years if enrolled in Israel continued-access addendum.

Adverse event reporting additional description

All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Galcanezumab 120mg - Double-Blind Treatment Phase

Reporting group description

Participants received loading dose of 240mg galcanezumab at first dosing visit followed by 120mg of galcanezumab once a month by subcutaneous injection for 2 months. 5 participants discontinued after receiving loading dose of 240mg. They were included under 240mg arm for safety analysis.

Reporting group title

Placebo - Double-Blind Treatment Phase

Reporting group description

Participants received placebo once a month by subcutaneous injection for 3 months.

Reporting group title

Galcanezumab 240mg - Double-Blind Treatment Phase

Reporting group description

Participants received placebo once a month by subcutaneous injection for 3 months.

Reporting group title

Galcanezumab 240mg/Galcanezumab - Open-Label Extension Phase

Reporting group description

After completion of Galcanezumab 240mg double-blind phase, participants had an option to enter open-label extension phase where they received 240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Reporting group title

Galcanezumab 120mg/Galcanezumab - Open-Label Extension Phase

Reporting group description

After completion of Galcanezumab 120mg double-blind phase, participants had an option to enter open-label extension phase where they received 240mg galcanezumab SC at first month, 120mg at second month followed by 120mg or 240mg once a month (at the discretion of the investigator) for the remaining 7 months.

Reporting group title

Placebo/Galcanezumab - Open-Label Extension Phase

Reporting group description

Reporting group title

Placebo - Follow-up Phase

Reporting group description

Participants entered follow-up phase from placebo double-blind treatment phase and were observed for 4 months. No treatments administered.

Reporting group title

Galcanezumab 120mg - Follow-up Phase

Reporting group description

Participants entered follow-up phase from Galcanezumab 120mg double-blind treatment phase and were observed for 4 months. No treatments administered. 1 participant discontinued from double-blind treatment phase after receiving 240mg loading dose and entered Follow-up phase. That participant was included under 240mg arm for safety analysis.

Reporting group title

Galcanezumab 240mg - Follow-up Phase

Reporting group description

Participants entered follow-up phase from from Galcanezumab 240mg double-blind treatment phase and were observed for 4 months. No treatments administered.

Reporting group title

Placebo/Galcanezumab - Follow-up Phase

Reporting group description

Participants entered follow-up phase from Placebo/Galcanezumabopen-label extension phase and were observed for 4 months. No treatments administered.

Reporting group title

Galcanezumab 120mg/Galcanezumab - Follow-up Phase

Reporting group description

Participants entered follow-up phase from Galcanezumab 120mg/Galcanezumab open-label extension phase and were observed for 4 months. No treatments administered.

Reporting group title

Galcanezumab 240mg/Galcanezumab - Follow-up Phase

Reporting group description

Participants entered follow-up phase from Galcanezumab 240mg/Galcanezumab open-label extension phase and were observed for 4 months. No treatments administered.

Reporting group title

Israel Addendum

Reporting group description

Galcanezumab 120mg - Double-Blind Treatment Phase

Placebo - Double-Blind Treatment Phase

Galcanezumab 240mg - Double-Blind Treatment Phase

Galcanezumab 240mg/Galcanezumab - Open-Label Extension Phase

Galcanezumab 120mg/Galcanezumab - Open-Label Extension Phase

Placebo/Galcanezumab - Open-Label Extension Phase

Placebo - Follow-up Phase

Galcanezumab 120mg - Follow-up Phase

Galcanezumab 240mg - Follow-up Phase

Placebo/Galcanezumab - Follow-up Phase

Galcanezumab 120mg/Galcanezumab - Follow-up Phase

Galcanezumab 240mg/Galcanezumab - Follow-up Phase

Israel Addendum

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 273 (0.73%)

5 / 558 (0.90%)

4 / 282 (1.42%)

9 / 262 (3.44%)

6 / 259 (2.32%)

16 / 501 (3.19%)

0 / 15 (0.00%)

0 / 4 (0.00%)

5 / 438 (1.14%)

3 / 223 (1.35%)

1 / 228 (0.44%)

6 / 29 (20.69%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

breast cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

colon cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 273 (0.37%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

lung adenocarcinoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

malignant nipple neoplasm

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

1 / 273 (0.37%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

oesophageal adenocarcinoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

squamous cell carcinoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tongue neoplasm malignant stage unspecified

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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 24.0

subjects affected / exposed ^[1]

0 / 232 (0.00%)

0 / 483 (0.00%)

0 / 231 (0.00%)

0 / 214 (0.00%)

0 / 218 (0.00%)

0 / 433 (0.00%)

0 / 14 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 376 (0.00%)

0 / 186 (0.00%)

0 / 184 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vascular disorders

deep vein thrombosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

varicose vein

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

abortion spontaneous

alternative dictionary used: MedDRA 24.0

subjects affected / exposed ^[2]

0 / 232 (0.00%)

1 / 483 (0.21%)

0 / 231 (0.00%)

0 / 214 (0.00%)

0 / 218 (0.00%)

0 / 433 (0.00%)

0 / 14 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 376 (0.00%)

0 / 186 (0.00%)

0 / 184 (0.00%)

0 / 25 (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

non-cardiac chest pain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

swelling face

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

dyspnoea

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

epistaxis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

1 / 558 (0.18%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

haemoptysis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pulmonary embolism

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

1 / 282 (0.35%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

1 / 223 (0.45%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

confusional state

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

foot fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

road traffic accident

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

skin laceration

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

congenital diaphragmatic hernia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

acute myocardial infarction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

angina unstable

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cardiac failure congestive

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

myocardial infarction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

1 / 558 (0.18%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ventricular extrasystoles

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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

migraine

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

orthostatic intolerance

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

seizure

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

iron deficiency anaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

abdominal adhesions

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abdominal pain lower

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

1 / 223 (0.45%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

abdominal pain upper

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

alcoholic pancreatitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

1 / 558 (0.18%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

gastritis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

1 / 558 (0.18%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

haematemesis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hiatus hernia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

nausea

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pancreatitis acute

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

1 / 282 (0.35%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

small intestinal obstruction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

volvulus

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

vomiting

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

cholelithiasis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

rash

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urticaria

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

1 / 228 (0.44%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

nephrolithiasis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

1 / 282 (0.35%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

renal colic

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

1 / 282 (0.35%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

tubulointerstitial nephritis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary retention

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

1 / 438 (0.23%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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

intervertebral disc protrusion

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

cellulitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

chronic tonsillitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

complicated appendicitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diverticulitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

osteomyelitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

pneumonia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

1 / 223 (0.45%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

upper respiratory tract infection

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

urinary tract infection

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

1 / 259 (0.39%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

vestibular neuronitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

1 / 29 (3.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

dehydration

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

0 / 262 (0.00%)

0 / 259 (0.00%)

1 / 501 (0.20%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

diabetic ketoacidosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

0 / 282 (0.00%)

1 / 262 (0.38%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

hypokalaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 273 (0.00%)

0 / 558 (0.00%)

1 / 282 (0.35%)

0 / 262 (0.00%)

0 / 259 (0.00%)

0 / 501 (0.00%)

0 / 15 (0.00%)

0 / 4 (0.00%)

0 / 438 (0.00%)

0 / 223 (0.00%)

0 / 228 (0.00%)

0 / 29 (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 specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
[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 specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

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

Non-serious adverse events	Galcanezumab 120mg - Double-Blind Treatment Phase	Placebo - Double-Blind Treatment Phase	Galcanezumab 240mg - Double-Blind Treatment Phase	Galcanezumab 240mg/Galcanezumab - Open-Label Extension Phase	Galcanezumab 120mg/Galcanezumab - Open-Label Extension Phase	Placebo/Galcanezumab - Open-Label Extension Phase	Placebo - Follow-up Phase	Galcanezumab 120mg - Follow-up Phase	Galcanezumab 240mg - Follow-up Phase	Placebo/Galcanezumab - Follow-up Phase	Galcanezumab 120mg/Galcanezumab - Follow-up Phase	Galcanezumab 240mg/Galcanezumab - Follow-up Phase	Israel Addendum
Total subjects affected by non serious adverse events
subjects affected / exposed	98 / 273 (35.90%)	170 / 558 (30.47%)	105 / 282 (37.23%)	120 / 262 (45.80%)	117 / 259 (45.17%)	223 / 501 (44.51%)	0 / 15 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	57 / 438 (13.01%)	19 / 223 (8.52%)	27 / 228 (11.84%)	26 / 29 (89.66%)
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 273 (0.73%)	0 / 558 (0.00%)	1 / 282 (0.35%)	2 / 262 (0.76%)	0 / 259 (0.00%)	1 / 501 (0.20%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	2	0	2	2	0	1	0	0	0	0	0	0	2
fatigue
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 273 (2.20%)	6 / 558 (1.08%)	7 / 282 (2.48%)	8 / 262 (3.05%)	1 / 259 (0.39%)	7 / 501 (1.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	3 / 438 (0.68%)	0 / 223 (0.00%)	1 / 228 (0.44%)	4 / 29 (13.79%)
occurrences all number	6	6	8	9	1	7	0	0	0	3	0	1	4
influenza like illness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 273 (1.47%)	3 / 558 (0.54%)	4 / 282 (1.42%)	2 / 262 (0.76%)	2 / 259 (0.77%)	5 / 501 (1.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	1 / 228 (0.44%)	4 / 29 (13.79%)
occurrences all number	4	3	4	3	2	5	0	0	0	0	0	1	7
injection site erythema
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 273 (1.47%)	5 / 558 (0.90%)	13 / 282 (4.61%)	10 / 262 (3.82%)	6 / 259 (2.32%)	12 / 501 (2.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	3 / 29 (10.34%)
occurrences all number	5	5	16	19	6	18	0	0	0	0	0	0	4
injection site pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	18 / 273 (6.59%)	24 / 558 (4.30%)	21 / 282 (7.45%)	5 / 262 (1.91%)	5 / 259 (1.93%)	8 / 501 (1.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	3 / 29 (10.34%)
occurrences all number	31	32	33	6	6	10	0	0	0	0	0	0	3
injection site reaction
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 273 (2.93%)	10 / 558 (1.79%)	15 / 282 (5.32%)	17 / 262 (6.49%)	21 / 259 (8.11%)	19 / 501 (3.79%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	3 / 29 (10.34%)
occurrences all number	13	16	19	33	56	51	0	0	0	0	0	0	4
peripheral swelling
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 273 (0.37%)	1 / 558 (0.18%)	1 / 282 (0.35%)	0 / 262 (0.00%)	0 / 259 (0.00%)	4 / 501 (0.80%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	1	1	1	0	0	6	0	0	0	0	0	0	2
pyrexia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 273 (1.83%)	1 / 558 (0.18%)	1 / 282 (0.35%)	3 / 262 (1.15%)	3 / 259 (1.16%)	5 / 501 (1.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	5	1	1	4	3	5	0	0	0	0	0	0	2
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 273 (1.47%)	3 / 558 (0.54%)	4 / 282 (1.42%)	9 / 262 (3.44%)	3 / 259 (1.16%)	8 / 501 (1.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	3 / 438 (0.68%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	4	3	4	9	3	9	0	0	0	3	0	0	2
oropharyngeal pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 273 (0.73%)	3 / 558 (0.54%)	4 / 282 (1.42%)	4 / 262 (1.53%)	5 / 259 (1.93%)	8 / 501 (1.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	1 / 223 (0.45%)	1 / 228 (0.44%)	6 / 29 (20.69%)
occurrences all number	2	3	4	4	5	10	0	0	0	0	1	1	7
pleural effusion
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Psychiatric disorders
sleep disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 273 (0.37%)	1 / 558 (0.18%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	1 / 228 (0.44%)	4 / 29 (13.79%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	1	4
Cardiac disorders
pericardial effusion
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 273 (2.20%)	19 / 558 (3.41%)	9 / 282 (3.19%)	7 / 262 (2.67%)	4 / 259 (1.54%)	10 / 501 (2.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 438 (0.23%)	0 / 223 (0.00%)	2 / 228 (0.88%)	3 / 29 (10.34%)
occurrences all number	7	20	10	11	5	10	0	0	0	2	0	3	4
headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 273 (1.47%)	8 / 558 (1.43%)	1 / 282 (0.35%)	2 / 262 (0.76%)	5 / 259 (1.93%)	7 / 501 (1.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 438 (0.23%)	0 / 223 (0.00%)	0 / 228 (0.00%)	3 / 29 (10.34%)
occurrences all number	4	9	1	3	5	7	0	0	0	1	0	0	4
hypoaesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	2 / 558 (0.36%)	1 / 282 (0.35%)	0 / 262 (0.00%)	1 / 259 (0.39%)	4 / 501 (0.80%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	1 / 228 (0.44%)	0 / 29 (0.00%)
occurrences all number	0	2	1	0	1	4	0	0	1	0	0	1	0
tremor
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	1 / 259 (0.39%)	2 / 501 (0.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	1	2	0	0	0	0	0	0	2
Ear and labyrinth disorders
vertigo
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 273 (0.37%)	0 / 558 (0.00%)	2 / 282 (0.71%)	2 / 262 (0.76%)	1 / 259 (0.39%)	5 / 501 (1.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	2 / 228 (0.88%)	2 / 29 (6.90%)
occurrences all number	1	0	2	2	1	5	0	0	0	0	0	2	2
Gastrointestinal disorders
ascites
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	1 / 282 (0.35%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	0
flatulence
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	1 / 259 (0.39%)	2 / 501 (0.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0	1	0	0	0	0
nausea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	9 / 273 (3.30%)	22 / 558 (3.94%)	8 / 282 (2.84%)	11 / 262 (4.20%)	4 / 259 (1.54%)	7 / 501 (1.40%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	1 / 223 (0.45%)	2 / 228 (0.88%)	4 / 29 (13.79%)
occurrences all number	12	26	8	12	5	8	0	0	0	2	1	2	4
Hepatobiliary disorders
cholelithiasis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	1 / 558 (0.18%)	1 / 282 (0.35%)	0 / 262 (0.00%)	0 / 259 (0.00%)	1 / 501 (0.20%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 438 (0.46%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0	1	2	0	0	0
Skin and subcutaneous tissue disorders
pruritus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	2 / 558 (0.36%)	1 / 282 (0.35%)	2 / 262 (0.76%)	4 / 259 (1.54%)	5 / 501 (1.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 438 (0.23%)	0 / 223 (0.00%)	0 / 228 (0.00%)	4 / 29 (13.79%)
occurrences all number	0	2	1	4	4	6	0	0	0	1	0	0	4
urticaria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 273 (0.73%)	3 / 558 (0.54%)	0 / 282 (0.00%)	1 / 262 (0.38%)	2 / 259 (0.77%)	8 / 501 (1.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	0 / 223 (0.00%)	1 / 228 (0.44%)	3 / 29 (10.34%)
occurrences all number	3	3	0	1	2	11	0	0	0	2	0	2	3
Renal and urinary disorders
renal cyst
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 273 (0.73%)	8 / 558 (1.43%)	5 / 282 (1.77%)	7 / 262 (2.67%)	5 / 259 (1.93%)	25 / 501 (4.99%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	7 / 438 (1.60%)	1 / 223 (0.45%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	2	8	5	9	6	28	0	0	0	7	1	0	4
back pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 273 (2.93%)	14 / 558 (2.51%)	2 / 282 (0.71%)	13 / 262 (4.96%)	13 / 259 (5.02%)	11 / 501 (2.20%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	4 / 223 (1.79%)	0 / 228 (0.00%)	3 / 29 (10.34%)
occurrences all number	9	15	2	13	13	12	0	0	0	2	4	0	4
neck pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	7 / 273 (2.56%)	7 / 558 (1.25%)	0 / 282 (0.00%)	12 / 262 (4.58%)	6 / 259 (2.32%)	3 / 501 (0.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	5 / 438 (1.14%)	1 / 223 (0.45%)	1 / 228 (0.44%)	3 / 29 (10.34%)
occurrences all number	8	7	0	13	6	3	0	0	0	5	1	1	3
pain in extremity
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 273 (1.10%)	5 / 558 (0.90%)	2 / 282 (0.71%)	4 / 262 (1.53%)	2 / 259 (0.77%)	10 / 501 (2.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	0 / 223 (0.00%)	3 / 228 (1.32%)	3 / 29 (10.34%)
occurrences all number	3	5	2	4	2	10	0	0	0	2	0	3	3
spinal osteoarthritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	1 / 558 (0.18%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	1 / 501 (0.20%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	1	0	0	0	0
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 273 (1.83%)	3 / 558 (0.54%)	1 / 282 (0.35%)	7 / 262 (2.67%)	7 / 259 (2.70%)	14 / 501 (2.79%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	2 / 223 (0.90%)	3 / 228 (1.32%)	3 / 29 (10.34%)
occurrences all number	5	3	1	8	7	14	0	0	0	2	2	3	3
covid-19
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2
gastroenteritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 273 (0.73%)	1 / 558 (0.18%)	2 / 282 (0.71%)	2 / 262 (0.76%)	7 / 259 (2.70%)	8 / 501 (1.60%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 438 (0.46%)	1 / 223 (0.45%)	1 / 228 (0.44%)	2 / 29 (6.90%)
occurrences all number	2	1	2	2	7	9	0	0	0	2	1	1	2
infectious mononucleosis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	1 / 29 (3.45%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1
influenza
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	15 / 558 (2.69%)	6 / 282 (2.13%)	12 / 262 (4.58%)	17 / 259 (6.56%)	14 / 501 (2.79%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	5 / 438 (1.14%)	2 / 223 (0.90%)	4 / 228 (1.75%)	0 / 29 (0.00%)
occurrences all number	0	16	6	13	21	15	0	0	0	5	2	4	0
nasopharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	18 / 273 (6.59%)	24 / 558 (4.30%)	9 / 282 (3.19%)	27 / 262 (10.31%)	24 / 259 (9.27%)	45 / 501 (8.98%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	11 / 438 (2.51%)	2 / 223 (0.90%)	1 / 228 (0.44%)	5 / 29 (17.24%)
occurrences all number	20	26	9	32	31	55	0	0	0	11	2	3	6
pancreas infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
pneumonia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 273 (0.37%)	1 / 558 (0.18%)	2 / 282 (0.71%)	1 / 262 (0.38%)	0 / 259 (0.00%)	1 / 501 (0.20%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	2 / 29 (6.90%)
occurrences all number	1	1	2	1	0	1	0	0	0	0	0	0	3
sinusitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 273 (1.47%)	5 / 558 (0.90%)	7 / 282 (2.48%)	10 / 262 (3.82%)	5 / 259 (1.93%)	16 / 501 (3.19%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	7 / 438 (1.60%)	1 / 223 (0.45%)	1 / 228 (0.44%)	2 / 29 (6.90%)
occurrences all number	4	5	7	11	7	17	0	0	0	7	2	1	2
upper respiratory tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 273 (2.93%)	14 / 558 (2.51%)	9 / 282 (3.19%)	18 / 262 (6.87%)	17 / 259 (6.56%)	27 / 501 (5.39%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	4 / 438 (0.91%)	2 / 223 (0.90%)	3 / 228 (1.32%)	2 / 29 (6.90%)
occurrences all number	10	14	9	23	21	31	0	0	0	4	2	3	2
urinary tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 273 (2.20%)	6 / 558 (1.08%)	5 / 282 (1.77%)	5 / 262 (1.91%)	6 / 259 (2.32%)	29 / 501 (5.79%)	0 / 15 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	9 / 438 (2.05%)	3 / 223 (1.35%)	3 / 228 (1.32%)	4 / 29 (13.79%)
occurrences all number	6	6	5	6	7	33	0	0	0	10	3	3	4
Metabolism and nutrition disorders
hypercalcaemia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 273 (0.00%)	0 / 558 (0.00%)	0 / 282 (0.00%)	0 / 262 (0.00%)	0 / 259 (0.00%)	0 / 501 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 438 (0.00%)	0 / 223 (0.00%)	0 / 228 (0.00%)	0 / 29 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

22 Jan 2016

-Study Design: Added language regarding the contents of each injection for the different treatment assignments in order to clarify how treatment is blinded. -Exclusion criteria: Excluded patients with a prior lifetime history of stroke to provide additional safeguards for patients who may be at risk for stroke. -Safety Monitoring: Added text to indicate that additional neurological examinations will be conducted to assess for possible cerebrovascular events, along with instructions for appropriate follow-up. - Blinding: Revised wording regarding procedures associated with emergency unblinding such that investigators no longer need to contact Lilly prior to emergency unblinding of a patient’s treatment assignment. - Concomitant therapy: Added the list of allowed and disallowed concomitant treatments. - Permanent Discontinuation from Study Treatment: Modified treatment discontinuation criteria to require (rather than recommend) discontinuation of treatment in the event of specific liver function test abnormalities, and added language to indicate the additional events requiring discontinuation from LY2951742 or placebo. - Determination of Sample size: Added assumptions of minimal sample size calculation; Added information regarding the approximate number of countries, investigative sites, and patients planned for inclusion in the study. - Key secondary analysis: Provided additional details regarding statistical control of the familywise type 1 error rate for the primary and key secondary endpoints. - Immunogenicity Analysis: Added clarification on the statistical model to be used for subgroup analyses.

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 Chronic Migraine - the REGAIN 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 (MHD)

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

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

Secondary: Number 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) Role-function Restrictive Domain

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) 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 the Patient Global Impression of Severity (PGI-S) Score

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

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Overall Mean Change from Baseline in Headache Hours

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

Secondary: Mean Change from Baseline on 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): Area Under the Concentration Time Curve (AUC) of Galcanezumab

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab

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

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

Secondary: Serum concentrations of Galcanezumab

Secondary: Serum concentrations of Galcanezumab

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Chronic Migraine - the REGAIN 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 (MHD)

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

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

Secondary: Number 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) Role-function Restrictive Domain

Secondary: Mean Change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) 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 the Patient Global Impression of Severity (PGI-S) Score

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

Secondary: Overall Mean Change from Baseline in Headache Hours

Secondary: Overall Mean Change from Baseline in Headache Hours

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

Secondary: Mean Change from Baseline on 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): Area Under the Concentration Time Curve (AUC) of Galcanezumab

Secondary: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab

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

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

Secondary: Serum concentrations of Galcanezumab

Secondary: Serum concentrations of Galcanezumab

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Chronic Migraine - the REGAIN Study.