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Clinical Trial Results:
Randomized Controlled Trial of Lasmiditan Over Four Migraine Attacks

Summary
EudraCT number	2018-001661-17
Trial protocol	GB NL DE DK CZ ES AT HU IT
Global end of trial date

Results information
Results version number	v1
This version publication date	28 Jun 2021
First version publication date	28 Jun 2021
Other versions	v2

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

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Trial information

Top of page

Sponsor protocol code

H8H-MC-LAIJ

ISRCTN number

US NCT number

NCT03670810

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 17131

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, United States, 46285

Public contact

Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-CTTLilly,

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

Interim

Date of interim/final analysis

12 Jun 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Jun 2020

Global end of trial reached?

Main objective of the trial

- To evaluate the efficacy of lasmiditan 200 mg and 100 mg on migraine headache pain freedom compared to placebo. - To evaluate the consistency of response to lasmiditan 200 mg and 100 mg compared to placebo.

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

24 Jun 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

China: 136

Country: Number of subjects enrolled

India: 39

Country: Number of subjects enrolled

Mexico: 95

Country: Number of subjects enrolled

Russian Federation: 38

Country: Number of subjects enrolled

United States: 82

Country: Number of subjects enrolled

Austria: 11

Country: Number of subjects enrolled

Belgium: 28

Country: Number of subjects enrolled

Denmark: 30

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Germany: 275

Country: Number of subjects enrolled

Hungary: 17

Country: Number of subjects enrolled

Italy: 22

Country: Number of subjects enrolled

Netherlands: 10

Country: Number of subjects enrolled

Spain: 61

Country: Number of subjects enrolled

Switzerland: 19

Country: Number of subjects enrolled

Czechia: 96

Country: Number of subjects enrolled

United Kingdom: 490

Worldwide total number of subjects

1471

EEA total number of subjects

572

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)

1431

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants were considered study completers after treating 4 migraine attacks or after completing 4 months of study duration regardless of number of treated attacks.

Screening details

An ITT evaluable attack is defined as a treated attack of least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose. Results for maximum extended enrollment will be posted after the study completion.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

100 mg Lasmiditan

Arm description

Arm type

Experimental

Investigational medicinal product name

Lamiditan

Investigational medicinal product code

LY573144

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received one 100 mg Lasmiditan tablet administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received one 50 mg Lasmiditan matching placebo tablet and one 100-mg Lasmiditan matching placebo tablet to maintain blind administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks..

200 mg Lasmiditan

Arm description

Arm type

Experimental

Investigational medicinal product name

Lasmiditan

Investigational medicinal product code

LY573144

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received two 100 mg Lasmiditan tablets administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received one 50 mg Lasmiditan matching placebo tablet to maintain blind. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Control 1 Sequence

Arm description

Arm type

Experimental

Investigational medicinal product name

Lasmiditan

Investigational medicinal product code

LY573144

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received one 50 mg Lasmiditan tablet administered orally to treat migraine attack 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received two 100 mg Lasmiditan matching placebo tablet to maintain blind for migraine attacks 1, 2 and 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Control 2 Sequence

Arm description

Arm type

Experimental

Investigational medicinal product name

Lasmiditan

Investigational medicinal product code

LY573144

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received one 50 mg Lasmiditan tablet administer orally to treat migraine attack 4. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received two 100 mg Lasmiditan matching placebo tablet to maintain blind for migraine attacks 1, 2, and 3. Tablets were administered orally within 4 hours of onset of a single migraine attack, up to 4 migraine attacks.

Number of subjects in period 1	100 mg Lasmiditan	200 mg Lasmiditan	Control 1 Sequence	Control 2 Sequence
Started	485	486	249	251
Treated at Least One Migraine Attack	485	486	249	251
Completed	381	369	208	213
Not completed	104	117	41	38
Consent withdrawn by subject	20	20	8	9
Physician decision	3	-	1	-
Adverse event, non-fatal	36	38	2	4
Pregnancy	1	1	-	-
Non-compliance with study drug	-	2	3	-
Lost to follow-up	6	6	4	6
Continuing Study	27	29	12	10
Missing	1	1	-	1
Lack of efficacy	8	8	3	4
Protocol deviation	2	12	8	4

Baseline characteristics

Top of page

Reporting group title

Overall Study

Reporting group description

Reporting group values	Overall Study	Total
Number of subjects	1471	1471
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	41.40 ( 12.40 )	-
Gender categorical
Units: Subjects
Female	1237	1237
Male	234	234
Ethnicity
Units: Subjects
Hispanic or Latino	135	135
Not Hispanic or Latino	1184	1184
Unknown or Not Reported	152	152
Race
Units: Subjects
American Indian or Alasks Native	80	80
Asian	221	221
Black or African American	27	27
Native Hawaiian or Other Pacific Islander	1	1
White	1117	1117
Multiple	3	3
Missing	22	22
Region of Enrollment
Units: Subjects
Austria	11	11
Belgium	28	28
China	136	136
Denmark	30	30
France	22	22
Germany	275	275
Hungary	17	17
India	39	39
Italy	22	22
Mexico	95	95
Netherlands	10	10
Russian Federation	38	38
Spain	61	61
Switzerland	19	19
United Kingdom	490	490
United States	82	82
Czechia	96	96

End points

Top of page

Reporting group title

100 mg Lasmiditan

Reporting group description

Reporting group title

200 mg Lasmiditan

Reporting group description

Reporting group title

Control 1 Sequence

Reporting group description

Reporting group title

Control 2 Sequence

Reporting group description

Subject analysis set title

Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants who received 50 mg Lasmiditan matching placebo to treat migraine attacks 1, 2 and 4 in Control 1 Sequence or attacks 1, 2, and 3 in Control 2 Sequence.

Subject analysis set title

Control

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants who received 50 mg Lasmiditan to treat migraine attack 3 in Control 1 Sequence and migraine attack 4 in Control 2 Sequence.

Primary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack

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End point title

Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack ^[1]

End point description

Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. Analysis Population Description (ADP): All randomized participants who used at least 1 dose of study drug for an Intent-to-Treat (ITT) evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Primary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)	25.8	29.3	8.4

Pain Free 2 Hours Postdose First Attack 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.83

Confidence interval

level

95%

sides

2-sided

lower limit

2.56

upper limit

8.73

Pain Free 2 Hours Postdose First Attack 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.56

Confidence interval

level

95%

sides

2-sided

lower limit

3.07

upper limit

6.77

Primary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Top of page

End point title

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks ^[2]

End point description

To evaluate the 2 out of 3 primary consistency endpoint, the results of ITT evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For participants with more than 3 ITT evaluable attacks, only the first 3 will be considered. Pain-free was defined as mild, moderate, or severe headache pain becoming none at the indicated assessment time. APD: All randomized participants who experienced at least 2 successes or 2 failures during their first 2 or 3 ITT evaluable attacks.

End point type

Primary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	340	336	373
Units: percentage of participants
number (not applicable)	14.4	24.4	4.3

Pain Free in at Least 2 Out of 3 Attacks 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

713

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.77

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

6.76

Pain Free in at Least 2 Out of 3 Attacks 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

709

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.01

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.24

Confidence interval

level

95%

sides

2-sided

lower limit

4.13

upper limit

12.67

Secondary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.

Top of page

End point title

Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders. ^[3]

End point description

Pain-free is defined as mild, moderate, or severe headache pain becoming none at 2 hours postdose during the first attack. A triptan insufficient responder is defined as: 1) Scoring ≤5 on 4 questions from the Migraine Treatment Optimization Questionnaire (mTOQ-6) that defines participants with poor or very poor response to their current regimen; 2) Indicated they obtained pain freedom at 2 hours in 0 out of 3, or 1 out of 3 attacks when treated with the most recent triptan, or 3)Are not currently taking triptan and discontinued their most recent triptan due to lack of efficacy, tolerability issue, or contradictions to a past triptan. APD: All randomized participants who were triptan insufficient responders and used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	183	203	193
Units: percentage of participants
number (not applicable)	24.0	25.6	8.8

Triptan Insufficient Responder 1st Attack 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

376

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.29

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

6.02

Triptan Insufficient Responder 1st Attack 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.97

upper limit

6.42

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders

Top of page

End point title

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders ^[4]

End point description

Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe at baseline to none at the indicated assessment time. A subject is not counted as being pain-free at a specific time point if she or he used rescue or recurrence medication at or before the specific time point. APD: All randomized participants who were triptan insufficient responders and experienced a sufficient number of successes or failures, (2 successes or 2 failures ) during their first 2 or 3 ITT-evaluable attacks.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	17	31	7
Units: percentage of participants
number (not applicable)	11.0	20.1	4.3

TIR 2 out 3 Attacks 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.31

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

6.78

TIR 2 Out of 3 Attacks 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.64

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

13.25

Secondary: Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack

Top of page

End point title

Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack ^[5]

End point description

Percentage of participants with no disability as measured by the disability item, at 2 hours postdose during the first attack. Disability was measured by determining the level of interference with normal activities with 4 response options including not at all; mild interference, marked interference; and need complete bed rest. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)	18.6	19.8	9.5

Disability Item 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.22

Confidence interval

level

95%

sides

2-sided

lower limit

1.48

upper limit

3.33

Disability Item 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.65

upper limit

3.67

Secondary: Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack

Top of page

End point title

Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack ^[6]

End point description

Sustained pain freedom defined as pain free at 2 and 24 hours with no rescue medication. APD: All randomized participants who received at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

24 Hours

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)	13.6	17.3	4.3

24 Hour Sustained Pain Freedom 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.52

Confidence interval

level

95%

sides

2-sided

lower limit

2.05

upper limit

6.02

24 Hour Sustained Pain Freedom 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.67

Confidence interval

level

95%

sides

2-sided

lower limit

2.77

upper limit

7.88

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Top of page

End point title

Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks ^[7]

End point description

Headache pain relief is defined as a reduction in pain severity from moderate to severe at baseline to mild or none at 2 hours postdose in at least 2 out of 3 attacks. To evaluate at least 2 out of 3 consistency endpoints, the results of ITT-evaluable attacks in the lasmiditan 100-mg and 200-mg groups will be assessed, and the ITT-evaluable attacks treated with placebo in the control group will be used for comparison. For patients with more than 3 ITT-evaluable attacks, only the first 3 with the same treatment will be considered. APD: All randomized participants who experienced a sufficient number of successes or failures, (2 successes or 2 failures ) during their first 2 or 3 ITT-evaluable attacks.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	332	333	320
Units: percentage of participants
number (not applicable)	62.3	66.7	36.9

Pain Relief 2 out of 3 Attacks 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

652

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

4.01

Pain Relief 2 out of 3 Attacks 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

653

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Confidence interval

level

95%

sides

2-sided

lower limit

2.53

upper limit

4.85

Secondary: Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack

Top of page

End point title

Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack ^[8]

End point description

MBS freedom is defined as the absence of the associated symptom of migraine (nausea, phonophobia, or photophobia) at the indicated assessment time that was identified at baseline as the most bothersome symptom. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	376	395	396
Units: percentage of participants
number (not applicable)	40.4	39.0	28.0

Free of MBS 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

772

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

2.35

Free of MBS 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

791

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.63

Confidence interval

level

90%

sides

2-sided

lower limit

1.21

upper limit

2.2

Secondary: Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack

Top of page

End point title

Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack ^[9]

End point description

Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time. APD: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)	65.4	65.2	41.3

Pain Relief 2 Hours Postdose 1st Attack 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.71

Confidence interval

level

95%

sides

2-sided

lower limit

2.05

upper limit

3.57

Pain Relief 2 Hours Postdose 1st Attack 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.68

Confidence interval

level

95%

sides

2-sided

lower limit

2.04

upper limit

3.53

Secondary: Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack

Top of page

End point title

Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack ^[10]

End point description

Percentage of participants requiring rescue medication for migraine within 2 to 24 hours of treatment during the first attack. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

24 Hours

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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	311	307	406
Units: percentage of participants
number (not applicable)	19.6	19.2	29.3

Rescue Medication 1st Attack 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

717

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

0.65

Rescue Medication 1st Attack 200 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

717

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.6

Secondary: Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack

Top of page

End point title

Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack ^[11]

End point description

Total migraine freedom is defined as no pain and no migraine associated symptoms (photophobia, phonophobia, nausea, and vomiting) at 2 hours postdose during the first attack. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

Notes
[11] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)	17.9	21.0	7.2

Free of Migraine Associated Symptoms 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.79

upper limit

4.28

Free of Migraine Associated Symptoms 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.37

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

5.15

Secondary: Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack

Top of page

End point title

Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack ^[12]

End point description

Percentage of participants with migraine recurrence at 24 hours during the first attack defined as return of any headache in participants who were pain free at 2 hours. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

24 hours

Notes
[12] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	108	127	37
Units: percentage of participants
number (not applicable)	30.6	22.0	37.8

No statistical analyses for this end point

Secondary: Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack

Top of page

End point title

Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack ^[13]

End point description

Percentage of participants with pain freedom, pain relief, freedom from MBS, and no disability postdose during first attack. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

30 Minutes (Min) and 1 Hour (Hr) Postdose

Notes
[13] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: Percentage of Participants
number (not applicable)
Pain Freedom (30 Min)	1.4	1.6	0.2
Pain Freedom (1 Hr)	6.0	12.7	2.0
Pain Relief (30 Min)	18.6	22.4	14.0
Pain Relief (1 Hr)	48.7	47.2	29.3
Freedom from MBS (30 Min)	12.5	14.4	11.4
Freedom from MBS (1 Hr)	23.7	28.9	22.0
No Disability Postdose During 1st Attack (30 Min)	3.1	2.3	2.3
No Disability Postdose During First Attack (1 Hr)	6.0	9.9	5.0

Pain Freedom 30 Min Postdose 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

53.37

Pain Freedom 30 Min. Postdose 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.065

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

59.08

Pain Freedom 1 Hour Postdose

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.42

upper limit

6.68

Pain Freedom 1 Hour Postdose

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.04

Confidence interval

level

95%

sides

2-sided

lower limit

3.43

upper limit

14.44

Pain Relief 30 Min Postdose 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.065

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

2.03

Pain Relief 30 Min Postdose 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

2.52

Pain Relief 1 Hour Postdose 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.74

upper limit

3.06

Pain Relief 1 Hour Postdose 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

1.64

upper limit

2.88

Freedom from MBS 30 Min 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.651

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.71

Freedom from MBS 30 Min 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.22

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.98

Freedom from MBS 1 Hour 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.593

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.54

Freedom from MBS 1 Hour 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.98

Secondary: Change from Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale

Top of page

End point title

Change from Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale ^[14]

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 5 items that reflect the number of days reported as missed, or with reduced productivity at work or home and social events. Each question is answered as the number of days during the past 3 months of assessment, ranging from 0 to 90, with the total score being the summation of the 5 numeric responses. A higher value is indicative of more disability. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

Baseline, Week 16

Notes
[14] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Control
Number of subjects analysed	447	437	451
Units: Score on a Scale
arithmetic mean (standard deviation)	-10.7 ( 24.36 )	-12.0 ( 21.38 )	-13.1 ( 21.40 )

Change from Baseline MIDAS 100 mg

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

898

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.092

Method

ANCOVA

Confidence interval

Change from Baseline MIDAS 200 mg

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

888

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.211

Method

ANCOVA

Confidence interval

Secondary: Percentage of Participants Very much Better or Much Better as Measured by Patient Global Impression of Change (PGI-C) at 2 Hours Postdose During the First Attack

Top of page

End point title

Percentage of Participants Very much Better or Much Better as Measured by Patient Global Impression of Change (PGI-C) at 2 Hours Postdose During the First Attack ^[15]

End point description

The PGI-C is a one-item questionnaire that asks participants to provide their impression of change since taking the medicine. The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Reported are participants whose combined impression of change since taking the medicine was very much better and much better at 2 hours postdose. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

Notes
[15] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: Percentage of Participants
number (not applicable)	29.8	30.0	13.3

PGI-C 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

2.01

upper limit

4.05

PGI-C 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.12

upper limit

4.26

Secondary: Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack

Top of page

End point title

Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack ^[16]

End point description

The 24-hour Migraine Quality of Life Questionnaire (24-hr MQoLQ) has been specifically developed to measure the HRQoL of patients with migraine within a 24-hour period after having taken migraine medication A domain score is calculated by summing the responses to the 3 questions and the domain score ranges from 3 to 21, with lower scores indicating less impairment. The questionnaire will be administered 24 hours after dosing with study drug during each migraine. The analysis of variance (ANOVA) model was used with region and treatment adjusted for the overall treatment effect. APD: All randomized participants who used at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

24 Hours Post First Dose

Notes
[16] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	289	303	293
Units: Score on a Scale
arithmetic mean (standard deviation)
Social Functioning	12.4 ( 4.8 )	12.1 ( 4.7 )	11.7 ( 4.7 )
Migraine Symptoms	12.4 ( 4.1 )	12.5 ( 4.2 )	11.4 ( 4.4 )
Feeling/Concern	11.2 ( 4.5 )	11.2 ( 4.5 )	10.3 ( 4.2 )

Social Functioning 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

582

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056

Method

ANOVA

Confidence interval

Social Functioning 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

596

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.267

Method

ANOVA

Confidence interval

Migraine Symptoms 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

582

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANOVA

Confidence interval

Migraine Symptoms 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

596

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

ANOVA

Confidence interval

Feeling/Concerns 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

582

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

ANOVA

Confidence interval

Feelings/Concerns 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

596

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

ANOVA

Confidence interval

Secondary: Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire

Top of page

End point title

Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire ^[17]

End point description

Treatment satisfaction was evaluated at the End of Study (EoS) visit by determining the participant's level of satisfaction (ranging from extremely dissatisfied to extremely satisfied); their willingness to take this treatment again (ranging from strongly disagree to strongly agree) and if they would they recommend this treatment to another participants (ranging from strongly disagree to strongly agree). APD: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

Week 16

Notes
[17] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Control
Number of subjects analysed	452	444	460
Units: Percentage of Participants
number (not applicable)
Recommend Treatment - Agree/Strongly Agree	57.2	58.1	52.0
Willing to Take Treatment - Agree/Strongly Agree	61.5	58.9	64.3
Extremely/Very Satisfied/Satisfied with Medication	48.9	51.6	43.5
Prefer This Treatment	31.2	32.7	29.1

Recommend Treatment - Agree/Strongly Agree 100 mg

Statistical analysis description

Agree and Strongly Agree

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

912

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.101

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.62

Recommend Treatment - Agree/Strongly Agree 200 mg

Statistical analysis description

Agree and Strongly Agree

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

904

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.063

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.67

Take Treatment Again - Agree/Strongly Agree 100 mg

Statistical analysis description

Agree and Strongly Agree

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

912

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.376

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.16

Take Treatment Again - Agree/Strongly Agree 200 mg

Statistical analysis description

Agree and Strongly Agree

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

904

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.082

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.03

Extremely/Very/ Satisfied with Medication 100 mg

Statistical analysis description

Extremely/Very Satisfied and Satisfied

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

912

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.096

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.62

Extremely/Very/ Satisfied with Medication 200 mg

Statistical analysis description

Extremely/Very Satisfied and Satisfied

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

904

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

1.8

PreferThis Treatment 100 mg

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

912

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.445

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.49

Prefer This Treatment 200 mg

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

904

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.243

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.58

Secondary: Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack

Top of page

End point title

Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack ^[18]

End point description

The EQ-5D-5L questionnaire is a participant-rated scale that assesses health status, it consists of 2 parts. The first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 5 possible levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems).The EQ-5D can be used to generate a health state index score, which is used to compute quality-adjusted life years for utilization in health economic analyses. The health state index score is calculated based on the responses to the 5 dimensions, providing a single value on a scale from less than 0 (where 0 is a health state equivalent to death) to 1 (perfect health), with higher scores indicating better health utility. ANCOVA was used to assess the effect of Lasmiditan over placebo or control. The model includes fixed categorical effect of treatment and geographic region and baseline as covariate.

End point type

Secondary

End point timeframe

Baseline, 24 hr Postdose APD: All randomized participants who use at least 1 dose of study drug for an ITT evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours pos

Notes
[18] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: Score on a Scale
arithmetic mean (standard deviation)	0.2499 ( 0.25788 )	0.2271 ( 0.29854 )	0.2122 ( 0.25729 )

EQ-5D-5L for First Attack

Comparison groups

100 mg Lasmiditan v 200 mg Lasmiditan v Placebo

Number of subjects included in analysis

1296

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.142

Method

ANCOVA

Confidence interval

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks

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End point title

Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks ^[19]

End point description

Headache pain-free is defined as a reduction in pain severity from mild, moderate, or severe to none at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all patients who experienced at least 3 successes or 2 failures during ITT-evaluable attacks. APD: All randomized participants who experienced a sufficient number of successes or failures, (3 out of 4 attacks) during ITT evaluable attacks for any of the consistency analyses.

End point type

Secondary

End point timeframe

2 Hours Postdose

Notes
[19] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Control
Number of subjects analysed	325	306	387
Units: Percentage of Participants
number (not applicable)	7.4	10.8	2.6

Pain Free 3 out of 4 Attacks 100 mg

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

712

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.01

Confidence interval

level

95%

sides

2-sided

lower limit

1.42

upper limit

6.4

Pain Free 3 out of 4 Attacks 200 mg

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

693

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.58

Confidence interval

level

95%

sides

2-sided

lower limit

2.22

upper limit

9.47

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks

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End point title

Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks ^[20]

End point description

Headache pain-relief is defined as a reduction in pain severity from moderate or severe at baseline to mild or none, or a reduction in pain severity from mild at baseline to none, at the indicated assessment time (2 hours postdose). To evaluate 3 out of 4 consistency endpoints; all ITT-evaluable attacks will be used. For the control group, the results of all ITT-evaluable attacks treated with lasmiditan 50 mg or placebo will be included. The control group is used for comparison. The population for 3 out of 4 consistency endpoints with sufficient number of successes or failures is defined as all patients who experienced at least 3 successes or 2 failures during ITT-evaluable attacks. APD: All randomized participants who experienced a sufficient number of successes or failures, (3 successes or 2 failures ) during ITT-evaluable attacks for any of the consistency analyses.

End point type

Secondary

End point timeframe

2 Hours Postdose

Notes
[20] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Control
Number of subjects analysed	260	235	317
Units: Percentage of Participants
number (not applicable)	40.8	49.8	21.8

Pain Relief 3 Out of 4 Attacks 100 mg

Comparison groups

100 mg Lasmiditan v Control

Number of subjects included in analysis

577

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.74

upper limit

3.62

Pain Relief 3 Out of 4 Attacks 200 mg

Comparison groups

200 mg Lasmiditan v Control

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.61

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

5.2

Secondary: Percentage of Participants with Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack

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End point title

Percentage of Participants with Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack ^[21]

End point description

Presence of associated migraine symptoms at 2 hours postdose at first migraine attack, including each of the following: phonophobia, photophobia, nausea, and vomiting. APD: All randomized participants who used at least 1 dose of study drug for an Intent-to-Treat (ITT) evaluable attack, defined as a treated attack of at least mild pain severity with any postdose pain severity assessments at or before 2 hours postdose.

End point type

Secondary

End point timeframe

2 Hours Postdose

Notes
[21] - 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: Subject analysis sets titled Placebo and Control were created to report results for participants who were randomized to the Control 1 and Control 2 arms.

End point values	100 mg Lasmiditan	200 mg Lasmiditan	Placebo
Number of subjects analysed	419	434	443
Units: percentage of participants
number (not applicable)
Nausea	29.1	29.0	29.1
Phonophobia	26.7	23.5	40.6
Photophobia	38.2	39.9	55.3
Vomiting	1.2	3.0	2.7

Nausea 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.953

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.36

Nausea 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.768

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.41

Phonophobia 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.71

Phonophobia 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.62

Photophobia 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

0.63

Photophobia 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.71

Vomiting 100 mg

Comparison groups

100 mg Lasmiditan v Placebo

Number of subjects included in analysis

862

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.129

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

1.25

Vomiting 200 mg

Comparison groups

200 mg Lasmiditan v Placebo

Number of subjects included in analysis

877

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.769

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

2.43

Adverse events

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Timeframe for reporting adverse events

Double Blind Phase

Adverse event reporting additional description

H8H-MC-LAIJ

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

100 mg Lasmiditan

Reporting group description

Participants received one 100 mg Lasmiditan tablet with one 50 mg Lasmiditan matching placebo tablet and one 100-mg Lasmiditan matching placebo tablet to maintain blind.

Reporting group title

200 mg Lasmiditan

Reporting group description

Participants received two 100 mg Lasmiditan tablets with one 50 mg Lasmiditan matching placebo tablet to maintain blind.

Reporting group title

Control

Reporting group description

Control 1: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 4 and one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind, for migraine attack 3. Control 2: Participants received one 50 mg Lasmiditan matching placebo tablet and two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attacks 1, 2, and 3, and one 50 mg Lasmiditan tablet with two 100 mg Lasmiditan matching placebo tablets to maintain blind for migraine attack 4.

Serious adverse events	100 mg Lasmiditan	200 mg Lasmiditan	Control
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 485 (1.44%)	8 / 486 (1.65%)	7 / 500 (1.40%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
lung adenocarcinoma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
nasopharyngeal cancer stage iii
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
hand fracture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ligament rupture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
lower limb fracture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
hemiplegic migraine
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
medication overuse headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
migraine
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
sensory loss
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
serotonin syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
vestibular migraine
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
endometriosis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[1]	0 / 403 (0.00%)	0 / 418 (0.00%)	1 / 416 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
heavy menstrual bleeding
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[2]	0 / 403 (0.00%)	1 / 418 (0.24%)	0 / 416 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
intermenstrual bleeding
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[3]	1 / 403 (0.25%)	0 / 418 (0.00%)	0 / 416 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
haemorrhoids thrombosed
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
tracheal mass
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
liver disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
suicidal ideation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
abscess oral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
appendicitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
bronchitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
otitis media
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[3] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	100 mg Lasmiditan	200 mg Lasmiditan	Control
Total subjects affected by non serious adverse events
subjects affected / exposed	328 / 485 (67.63%)	352 / 486 (72.43%)	184 / 500 (36.80%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
basal cell carcinoma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
uterine leiomyoma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[4]	0 / 403 (0.00%)	0 / 418 (0.00%)	1 / 416 (0.24%)
occurrences all number	0	0	1
Vascular disorders
flushing
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	4	0	0
hot flush
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	2 / 486 (0.41%)	4 / 500 (0.80%)
occurrences all number	5	2	4
hypertension
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	0	1	1
peripheral coldness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
poor peripheral circulation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
raynaud's phenomenon
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
Surgical and medical procedures
antibiotic prophylaxis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
tooth repair
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	22 / 485 (4.54%)	30 / 486 (6.17%)	3 / 500 (0.60%)
occurrences all number	30	51	4
chest discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	4 / 486 (0.82%)	3 / 500 (0.60%)
occurrences all number	5	7	3
chills
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	5 / 486 (1.03%)	3 / 500 (0.60%)
occurrences all number	6	5	4
discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	7 / 486 (1.44%)	1 / 500 (0.20%)
occurrences all number	5	11	1
fatigue
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	53 / 485 (10.93%)	72 / 486 (14.81%)	19 / 500 (3.80%)
occurrences all number	75	106	21
feeling abnormal
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	9 / 485 (1.86%)	19 / 486 (3.91%)	2 / 500 (0.40%)
occurrences all number	9	25	2
feeling drunk
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	6	2	0
feeling cold
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	1 / 486 (0.21%)	2 / 500 (0.40%)
occurrences all number	9	1	2
feeling hot
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	6 / 486 (1.23%)	2 / 500 (0.40%)
occurrences all number	4	8	2
feeling of body temperature change
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
feeling of relaxation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	2	0
gait disturbance
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	4 / 486 (0.82%)	0 / 500 (0.00%)
occurrences all number	5	4	0
general physical health deterioration
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
hunger
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
illness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	0	2	1
influenza like illness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	1	2	0
malaise
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 485 (1.24%)	7 / 486 (1.44%)	2 / 500 (0.40%)
occurrences all number	9	9	2
non-cardiac chest pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	2	1	1
oedema peripheral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	3	2	1
peripheral swelling
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	2 / 500 (0.40%)
occurrences all number	0	0	2
pyrexia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	2 / 500 (0.40%)
occurrences all number	0	3	2
sensation of blood flow
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
sensation of foreign body
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
sense of oppression
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
swelling face
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
thirst
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	3 / 486 (0.62%)	1 / 500 (0.20%)
occurrences all number	2	3	1
Immune system disorders
anaphylactic reaction
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
seasonal allergy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
Reproductive system and breast disorders
dysmenorrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[5]	1 / 403 (0.25%)	0 / 418 (0.00%)	0 / 416 (0.00%)
occurrences all number	1	0	0
erection increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[6]	0 / 82 (0.00%)	1 / 68 (1.47%)	0 / 84 (0.00%)
occurrences all number	0	1	0
intermenstrual bleeding
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[7]	0 / 403 (0.00%)	0 / 418 (0.00%)	1 / 416 (0.24%)
occurrences all number	0	0	1
menstrual disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[8]	1 / 403 (0.25%)	0 / 418 (0.00%)	0 / 416 (0.00%)
occurrences all number	1	0	0
menstruation irregular
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[9]	0 / 403 (0.00%)	1 / 418 (0.24%)	0 / 416 (0.00%)
occurrences all number	0	1	0
polymenorrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[10]	0 / 403 (0.00%)	0 / 418 (0.00%)	1 / 416 (0.24%)
occurrences all number	0	0	1
vaginal haemorrhage
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[11]	0 / 403 (0.00%)	1 / 418 (0.24%)	0 / 416 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	2 / 500 (0.40%)
occurrences all number	0	2	4
dry throat
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
dyspnoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	4	2	1
dysphonia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
epistaxis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	2	0	0
nasal congestion
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
oropharyngeal pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	3	0	1
rhinorrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
sinonasal obstruction
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
sinus pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
Psychiatric disorders
abnormal dreams
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	6 / 486 (1.23%)	1 / 500 (0.20%)
occurrences all number	5	9	1
agitation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	4 / 486 (0.82%)	1 / 500 (0.20%)
occurrences all number	2	4	1
aggression
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	2	0	0
apathy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
anxiety
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 485 (1.24%)	10 / 486 (2.06%)	4 / 500 (0.80%)
occurrences all number	8	10	4
attention deficit hyperactivity disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
confusional state
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	6 / 486 (1.23%)	0 / 500 (0.00%)
occurrences all number	2	6	0
depressed mood
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	7 / 486 (1.44%)	3 / 500 (0.60%)
occurrences all number	4	8	3
depression
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	0	1	1
depressive symptom
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
derealisation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
disorientation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	3	3	0
dyssomnia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
emotional disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
emotional distress
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
euphoric mood
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	3 / 486 (0.62%)	1 / 500 (0.20%)
occurrences all number	2	4	2
fear
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
hallucination
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
hallucination, auditory
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	2	0
hallucination, visual
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	6 / 486 (1.23%)	0 / 500 (0.00%)
occurrences all number	7	6	0
insomnia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 485 (1.24%)	11 / 486 (2.26%)	3 / 500 (0.60%)
occurrences all number	8	20	3
irritability
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	1	2	0
mood altered
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
nervousness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	0	2	1
nightmare
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	4 / 486 (0.82%)	1 / 500 (0.20%)
occurrences all number	4	5	1
poor quality sleep
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
restlessness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	6 / 486 (1.23%)	3 / 500 (0.60%)
occurrences all number	3	9	3
sleep disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	5 / 486 (1.03%)	0 / 500 (0.00%)
occurrences all number	1	7	0
somatic symptom disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	3	0	0
suicidal ideation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
Investigations
blood cholesterol increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
blood creatinine increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
electrocardiogram t wave abnormal
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
gamma-glutamyltransferase increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
heart rate increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	5	1	1
heart rate decreased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
intraocular pressure increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
muscle strength abnormal
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
pulse abnormal
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
total bile acids increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
Injury, poisoning and procedural complications
epicondylitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
fall
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
joint dislocation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
ligament sprain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
limb injury
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	1	0	1
muscle rupture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
rib fracture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
Cardiac disorders
bradycardia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	0	1	1
cardiovascular disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
palpitations
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	12 / 485 (2.47%)	7 / 486 (1.44%)	3 / 500 (0.60%)
occurrences all number	19	9	3
supraventricular extrasystoles
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
supraventricular tachycardia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
tachycardia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	5	1	0
Nervous system disorders
allodynia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
altered state of consciousness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	3	0
amnesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
anosmia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
aphasia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	1	3	0
ataxia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	1	3	0
autonomic nervous system imbalance
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
balance disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	10 / 485 (2.06%)	14 / 486 (2.88%)	2 / 500 (0.40%)
occurrences all number	16	16	2
bradykinesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
burning sensation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
cervical cord compression
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
cognitive disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	1	2	0
clumsiness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
coordination abnormal
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	2	4	0
depressed level of consciousness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	2	0	0
disturbance in attention
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	7 / 485 (1.44%)	11 / 486 (2.26%)	1 / 500 (0.20%)
occurrences all number	9	11	1
dizziness postural
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	0 / 486 (0.00%)	2 / 500 (0.40%)
occurrences all number	4	0	2
dizziness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	154 / 485 (31.75%)	182 / 486 (37.45%)	44 / 500 (8.80%)
occurrences all number	227	320	59
dysaesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
dyskinesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	0	2	0
dysgeusia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	1	1	1
dysarthria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	7 / 486 (1.44%)	0 / 500 (0.00%)
occurrences all number	1	7	0
fine motor skill dysfunction
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	0	3	0
formication
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	4	2	0
head discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	2 / 486 (0.41%)	2 / 500 (0.40%)
occurrences all number	4	3	2
headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	9 / 485 (1.86%)	9 / 486 (1.85%)	7 / 500 (1.40%)
occurrences all number	9	10	8
hemiparesis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
hypersomnia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	3	4	0
hypoaesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	24 / 485 (4.95%)	16 / 486 (3.29%)	7 / 500 (1.40%)
occurrences all number	33	24	9
hypotonia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	1	3	0
lethargy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	7 / 486 (1.44%)	0 / 500 (0.00%)
occurrences all number	6	11	0
memory impairment
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	2	0	2
mental impairment
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
migraine
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	1 / 486 (0.21%)	2 / 500 (0.40%)
occurrences all number	4	1	2
migraine with aura
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
muscle contractions involuntary
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
muscle spasticity
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
myoclonus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
paraesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	70 / 485 (14.43%)	93 / 486 (19.14%)	21 / 500 (4.20%)
occurrences all number	102	170	25
presyncope
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	4	2	1
psychomotor hyperactivity
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
restless legs syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	4 / 486 (0.82%)	1 / 500 (0.20%)
occurrences all number	6	6	1
sciatica
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	0	1	1
sedation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	3	0	0
sensory disturbance
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
serotonin syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
slow speech
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	0	2	0
somnolence
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	32 / 485 (6.60%)	54 / 486 (11.11%)	12 / 500 (2.40%)
occurrences all number	47	82	12
speech disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	0	3	0
taste disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
tension headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	2	1	2
tremor
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	9 / 485 (1.86%)	12 / 486 (2.47%)	3 / 500 (0.60%)
occurrences all number	9	19	3
Ear and labyrinth disorders
acute vestibular syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	2	0
deafness transitory
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
ear discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	2	0	0
ear pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
hyperacusis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	1	0	1
tinnitus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	9 / 486 (1.85%)	1 / 500 (0.20%)
occurrences all number	5	10	1
vertigo
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	44 / 485 (9.07%)	47 / 486 (9.67%)	7 / 500 (1.40%)
occurrences all number	66	79	7
vertigo positional
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	3	0	0
Eye disorders
abnormal sensation in eye
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
blepharospasm
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
diplopia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	0	4	0
eye pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
eye movement disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
eye pruritus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
eyelid ptosis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
metamorphopsia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
mydriasis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
ocular discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
ocular hyperaemia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
photophobia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	4 / 486 (0.82%)	1 / 500 (0.20%)
occurrences all number	3	5	1
photopsia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	5 / 486 (1.03%)	0 / 500 (0.00%)
occurrences all number	3	6	0
pupillary reflex impaired
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
vision blurred
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	5 / 485 (1.03%)	9 / 486 (1.85%)	0 / 500 (0.00%)
occurrences all number	5	12	0
visual impairment
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	7 / 486 (1.44%)	0 / 500 (0.00%)
occurrences all number	2	11	0
Gastrointestinal disorders
abdominal distension
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
abdominal discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	3 / 486 (0.62%)	1 / 500 (0.20%)
occurrences all number	0	4	1
abdominal pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	3 / 486 (0.62%)	1 / 500 (0.20%)
occurrences all number	4	3	1
abdominal pain upper
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	4 / 486 (0.82%)	11 / 500 (2.20%)
occurrences all number	1	6	14
diarrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 485 (1.24%)	6 / 486 (1.23%)	8 / 500 (1.60%)
occurrences all number	8	9	9
dry mouth
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	6 / 485 (1.24%)	11 / 486 (2.26%)	1 / 500 (0.20%)
occurrences all number	9	15	3
dyspepsia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	3 / 486 (0.62%)	2 / 500 (0.40%)
occurrences all number	3	3	2
epigastric discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
flatulence
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	1	2	1
gastritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	2 / 500 (0.40%)
occurrences all number	2	0	3
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	1 / 500 (0.20%)
occurrences all number	0	5	1
glossodynia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
hypoaesthesia oral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	6 / 486 (1.23%)	2 / 500 (0.40%)
occurrences all number	3	6	4
irritable bowel syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
mouth ulceration
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
nausea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	54 / 485 (11.13%)	70 / 486 (14.40%)	29 / 500 (5.80%)
occurrences all number	65	103	34
paraesthesia oral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	3 / 486 (0.62%)	2 / 500 (0.40%)
occurrences all number	4	3	3
toothache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	0 / 500 (0.00%)
occurrences all number	0	2	0
vomiting
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	12 / 485 (2.47%)	18 / 486 (3.70%)	11 / 500 (2.20%)
occurrences all number	13	22	13
Skin and subcutaneous tissue disorders
cold sweat
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	1	3	0
erythema
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	2
hyperhidrosis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	3 / 486 (0.62%)	4 / 500 (0.80%)
occurrences all number	4	4	5
night sweats
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
photosensitivity reaction
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
pruritus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	3	0	1
rash
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
skin burning sensation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
skin lesion
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
Renal and urinary disorders
chromaturia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
nephrolithiasis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
pollakiuria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
renal pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	2 / 486 (0.41%)	3 / 500 (0.60%)
occurrences all number	0	2	3
back pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	3 / 486 (0.62%)	3 / 500 (0.60%)
occurrences all number	2	3	3
bone pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
bursitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
costochondritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
joint stiffness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
limb discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 485 (1.65%)	8 / 486 (1.65%)	2 / 500 (0.40%)
occurrences all number	12	11	2
mobility decreased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
muscle fatigue
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
muscle spasms
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	7 / 486 (1.44%)	4 / 500 (0.80%)
occurrences all number	5	7	4
muscle tightness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
muscle twitching
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	6 / 486 (1.23%)	1 / 500 (0.20%)
occurrences all number	5	9	1
muscular weakness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	22 / 485 (4.54%)	29 / 486 (5.97%)	2 / 500 (0.40%)
occurrences all number	32	45	3
musculoskeletal pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
musculoskeletal chest pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
musculoskeletal stiffness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	1	0	1
myalgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	2	1	0
neck pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 485 (0.41%)	3 / 486 (0.62%)	4 / 500 (0.80%)
occurrences all number	2	3	4
osteoarthritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
pain in extremity
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	1	4	0
synovial cyst
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
Infections and infestations
bacterial vaginosis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed ^[12]	1 / 403 (0.25%)	1 / 418 (0.24%)	0 / 416 (0.00%)
occurrences all number	1	1	0
bronchitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
conjunctivitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
cystitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
diverticulitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
febrile infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
gastroenteritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	1 / 500 (0.20%)
occurrences all number	0	1	1
gastroenteritis viral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
influenza
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	3 / 486 (0.62%)	2 / 500 (0.40%)
occurrences all number	0	3	2
laryngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	2 / 500 (0.40%)
occurrences all number	0	0	2
lower respiratory tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
nasopharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 485 (1.65%)	8 / 486 (1.65%)	9 / 500 (1.80%)
occurrences all number	8	8	9
oral herpes
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	3 / 500 (0.60%)
occurrences all number	0	0	3
otitis externa
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
periodontitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
pharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
pulpitis dental
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
rhinitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	3 / 485 (0.62%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	3	0	0
skin infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0
upper respiratory tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	8 / 485 (1.65%)	2 / 486 (0.41%)	4 / 500 (0.80%)
occurrences all number	8	2	4
urinary tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	1	1	0
viral upper respiratory tract infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 485 (0.21%)	0 / 486 (0.00%)	0 / 500 (0.00%)
occurrences all number	1	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	4 / 485 (0.82%)	3 / 486 (0.62%)	0 / 500 (0.00%)
occurrences all number	4	4	0
food craving
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
hyperuricaemia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
hypoglycaemia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	0 / 486 (0.00%)	1 / 500 (0.20%)
occurrences all number	0	0	1
increased appetite
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 485 (0.00%)	1 / 486 (0.21%)	0 / 500 (0.00%)
occurrences all number	0	1	0

Notes
[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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[6] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[7] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[8] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[9] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[10] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[11] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
[12] - 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: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

More information

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Were there any global substantial amendments to the protocol? Yes

07 May 2018

Amendment (a): Changes in design of the trial (options for second dose and related secondary objectives were removed), Change of an exclusion criterion (removal of exclusion criteria #17: exclusion of patients with hepatitis/HIV), Change to duration (optional open label extension for up to one year)

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: Randomized Controlled Trial of Lasmiditan Over Four Migraine Attacks

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack

Primary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack

Primary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Primary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Secondary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.

Secondary: Percentage of Participants That Are Pain Free 2 Hours Postdose During the First Attack in Triptan Insufficient Responders.

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 2 Out of 3 Attacks in Triptan Insufficient Responders

Secondary: Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants With no Disability as Measured by the Disability Item, at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack

Secondary: Percentage of Participants With 24-Hour Sustained Pain Freedom During the First Attack

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 2 Out of 3 Attacks

Secondary: Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants Free of Most Bothersome Symptom (MBS) Associated With Migraine at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack

Secondary: Percentage of Participants With Pain Relief at 2 Hours Post Dose During the First Attack

Secondary: Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack

Secondary: Percentage of Participants Requiring Rescue Medication for Migraine Within 24 Hours of Treatment During the First Attack

Secondary: Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants That Are Free of Symptoms Associated With Migraine at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack

Secondary: Percentage of Participants With Migraine Recurrence at 24 Hours During the First Attack

Secondary: Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack

Secondary: Percentage of Participants With Pain Freedom, Pain Relief, Freedom From MBS, and No Disability Postdose During First Attack

Secondary: Change from Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale

Secondary: Change from Baseline in Total Score as Measured by the Migraine Disability Assessment Test (MIDAS) Scale

Secondary: Percentage of Participants Very much Better or Much Better as Measured by Patient Global Impression of Change (PGI-C) at 2 Hours Postdose During the First Attack

Secondary: Percentage of Participants Very much Better or Much Better as Measured by Patient Global Impression of Change (PGI-C) at 2 Hours Postdose During the First Attack

Secondary: Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack

Secondary: Migraine Quality of Life Questionnaire (MQoLQ) Score at 24 Hours Post First Dose of Study During First Attack

Secondary: Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire

Secondary: Percentage of Participants Satisfied With Their Treatment Measured by a 4-Item Questionnaire

Secondary: Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack

Secondary: Change From Baseline in Utility at 24 Hours Postdose as Measured by the EuroQol 5-Dimension 5-Level Scale (EQ-5D-5L) at 24 Hours Postdose During First Attack

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks

Secondary: Percentage of Participants That Are Pain Free at 2 Hours Postdose in at Least 3 Out of 4 Attacks

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks

Secondary: Percentage of Participants With Pain Relief at 2 Hours Postdose in at Least 3 Out of 4 Attacks

Secondary: Percentage of Participants with Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack

Secondary: Percentage of Participants with Associated Migraines Symptoms of Nausea, Vomiting, Photophobia, and Phonophobia Present at 2 Hours Postdose for First Attack

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Randomized Controlled Trial of Lasmiditan Over Four Migraine Attacks