A Randomized, Sham-controlled Study of gammaCore ® (nVNS)... | NCT02378844

Label	Type	Description	Intervention Names
gammaCore®-R	Active Comparator	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).	Device: gammaCore®-R
gammaCore®-R Sham	Sham Comparator	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).	Device: gammaCore®-R Sham

Name	Type	Description	Arm Group Labels	Other Names
gammaCore®-R	Device	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Measure	Description	Time Frame
Change in the Number of Migraine Days	Change in number of migraine days (as reported in subject diary), comparing the 4 week run-in period to the last 4 weeks in the randomized period.	last 4 weeks of the randomized/controlled period compared to the subject's own 4-week run-in period.

Measure	Description	Time Frame
Number of Participants With 50% Responder Rate	The number of subjects with a reduction of 50% or more in number of migraine days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period.	The last four weeks in the randomization period compared to the four week run-in period.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is between the ages of 18 and 75 years.
Has been previously diagnosed with migraine (with or without aura) in accordance with the International Classification of Headache Disorders (ICHD)-3 Beta Classification criteria.
Experience between 5 and 12 migraine days per month (over the last 4 months) with at least 2 of the migraines lasting more than 4 hours.
Has age of onset of migraine less than 50 years old.
Agrees not to use any migraine prevention treatments (including Botox injections) and/or medications (exclusive of medications taken for acute relief of migraine symptoms).
Agrees to refrain from initiating or changing the type, dosage or frequency of any prophylactic medications for indications other than migraine that in the opinion of the clinician may interfere with the study objectives (e.g. antidepressant, anti convulsant, beta blockers, etc.).
Agrees to use the gammaCore®-R device as intended, follow all of the requirements of the study including follow-up visit requirements, record required study data in the subject dairy, and other self-assessment questionnaires.
Is able to provide written Informed Consent.

Exclusion Criteria:

Has a concomitant medical condition that will require oral or injectable steroids during the study.
Has a history of any intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
Has a structural abnormality at the gammaCore®-R treatment site (e.g lymphadenopathy previous surgery or abnormal anatomy).
Has pain at the gammaCore®-R treatment site (e.g.dysesthesia, neuralgia and/or cervicalgia).
Has other significant pain problem (e.g.cancer pain, fibromyalgia or other head or facial disorder) that in the opinion of the investigator may confound the study assessments
Has know or suspected severe cardiac disease(e.g. symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure (CHF)).
Has known or suspected severe cerebrovascular disease, (e.g. prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery).
Has an abnormal baseline Electrocardiogram (ECG) e.g. second and third degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction).
Has had a cervical vagotomy.
Has uncontrolled high blood pressure (systolic >160 diastolic > 100 after 3 repeated measurements within 24 hours).
Is currently implanted with an electrical and/or neurostimulator device (e.g. cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator cochlear implant, Sphenopalatine ganglion stimulator or Occipital nerve stimulator).
Has been implanted with metal cervical spine hardware or has a metallic implant near the gammaCore®-R stimulation site.
Has a known history of suspicion of secondary headache.
Has a history of syncope (within the last five years).
Has a history of seizures (within the last five years).
Has a known or suspicion of substance abuse or addiction (within the last 5 years).
Is using marijuana (including medical marijuana) for any indications, more than twice a month.
Currently takes simple analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) greater than 15 days per month or triptans, ergots or combined analgesics greater than 10 days per month for headaches or other body pain.
Currently takes prescription opioids greater than 2 days per month for headaches or body pain.
Has taken medications for migraine prophylaxis in the previous 30 days.
Has previous diagnosis of medication overuse headache (MoH) , which has reverted to episodic migraine within the last 6 months.
Meets the ICHD-3 Beta Classification criteria for chronic migraine (> 15 headache days per month).
Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for the prophylaxis of migraine .
Has had surgery for migraine prevention.
Has undergone nerve block (occipital or other) in the head or neck within the last 2 months.
Has received Botox injections within the last 6 months.
Is pregnant or thinking of becoming pregnant during the study period, or of childbearing years and is unwilling to use and accepted form of birth control.
Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self- assessments is compromised (e.g. homeless, developmentally disabled and prisoner).
Is a relative of or an employee of the investigator or the clinical study site.
Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study.
Has previously used the gammaCore® device.

Name	Affiliation	Role
Hans-Christoph Diener, Professor	Universtätsklinikum Essen	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Neurology Department, University of Liège		Liège		BE-4000	Belgium
Danish Headache Center

PubMed Identifier	Type	Citation	Retractions
31522546	Derived	Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Lainez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia. 2019 Oct;39(12):1475-1487. doi: 10.1177/0333102419876920. Epub 2019 Sep 15.

ID	Title	Description
FG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 1, 2017	Jul 16, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in the Number of Migraine Days

Change in number of migraine days (as reported in subject diary), comparing the 4 week run-in period to the last 4 weeks in the randomized period.

Randomized population, Intention to Treat (ITT)

Posted

Mean

Standard Deviation

Days

last 4 weeks of the randomized/controlled period compared to the subject's own 4-week run-in period.

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Units	Counts
Participants	OG000165 OG001167

Title

Denominators

Categories

Title	Measurements
	OG000-1.98± 3.031 OG001-1.53± 3.090

Secondary

Number of Participants With 50% Responder Rate

The number of subjects with a reduction of 50% or more in number of migraine days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period.

Randomized population, Intention to Treat (ITT)

Posted

Count of Participants

Participants

The last four weeks in the randomization period compared to the four week run-in period.

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Mean Change in Number of Headache Days

The mean change in number of headache days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period.

Randomized population, Intention to Treat (ITT)

Posted

Mean

Standard Deviation

Days

The last four weeks in the randomization period compared to the four week run-in period.

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Change in Number of Acute Medication Days

The mean change in number of acute medication days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period

Randomized population, Intention to Treat (ITT)

Posted

Mean

Standard Deviation

acute medication days

The last four weeks in the randomization period compared to the four week run-in period.

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Change in Headache Disability Using Headache Impact Test-6

Change in headache disability from the 4 week run-in period to the last 4 weeks of the randomized period as measured using the Headache Impact Test-6 (HIT-6). The HIT-6 measures the impact if a subject's headaches on their ability to function at work, at home and in social situations. Subjects are presented with 6 questions about ability to function and normal daily life and for each question they rate the impact of their headaches as 'never' (6 points) or 'rarely' (9 points) or 'sometimes' (10 points) or 'very often' (11 points) or 'always' (13 points). Minimum score = 36, maximum score = 78. A higher score indicates more impact.

Randomized population, Intention to Treat (ITT) In the active group 23 subjects had missing data, in the sham group 32 subjects had missing data at the end of the randomized period

Posted

Mean

Full Range

units on a scale

From four week run-in period to last four weeks in the randomization period

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Number of Participants According to Grade on the Migraine Disability Assessment (MIDAS) Before and After Randomized Period

Migraine Disability Assessment (MIDAS) score from the end of run-in period to the end of randomized period. The MIDAS assessment measures the effect of headaches on a subject's daily functioning. It takes into account the past 3 months and is comprised of five questions. A lower score indicated less disability, a higher score indicates more disability. The scores are graded:

0-5, MIDAS Grade I, little disability 6-10, MIDAS Grade II, mild disability 11 to 20 MIDAS Grade III, moderate disability 21+ MIDAS Grade IV, severe disability

Randomized population, Intention to Treat (ITT) At randomisation (visit 2) subject numbers are 165 gammaCore-R and 167 gammaCore-R Sham.

At visit 6 the numbers are lower due to early subject discontinuation: 141 gammaCore-R and 132 gammaCore-R Sham

Posted

Number

participants

3 months - end of run-in period to end of randomized period

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Compare Changes in Quality of Life EuroQol Questionnaire 5 Dimensions and 5 Levels (EQ-5D-5L)

The descriptive system comprises five dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Each dimension has 5 levels (5L): no problems (1) , slight problems (2), moderate problems (3), severe problems (4) and extreme problems (5).

Minimum score is 5 (no problems) and maximum score is 25 (extreme problems)

An overall health question is asked using a visual analogue scale(VAS) from 0-100 where 0 is bad health and 100 good health

Randomized population, Intention to Treat (ITT) In the active group 24 subjects had missing data, in the sham group 35 subjects had missing data at the end of the randomized period

Posted

Mean

Full Range

scores on a scale

From four week run-in period to last four weeks in the randomization period

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001

Secondary

Change in Migraine Days in the Open Label Period (Adjusted ANCOVA)

Change in number of migraine days (as reported in subject diary) during the 6 month open label period compared to the baseline run-in period.

Randomized population (Intent to treat)

Posted

Mean

Full Range

Days

The 6 month open-label period compared to the four week run-in period

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Number of Participants With Adverse Events

Adverse Effects were collected for all subjects for the duration of the study.

Safety population

Posted

Count of Participants

Participants

up to Week 36

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Secondary

Change in Headache Days in the Open Label Period

The mean change in number of headache days (as reported in the subject diary) during the open label period compared to the base-line run-in period

Randomized population (Intent to treat)

Posted

Mean

95% Confidence Interval

Days

The 6 month open-label period compared to the four week run-in period

ID	Title	Description
OG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
OG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG0031 events1 affected277 at risk
Angina pectoris	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0005 events4 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Tachyarrhythmia	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0021 events1 affected136 at risk EG003
External ear pain	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Vertigo positional	Ear and labyrinth disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Adrenomegaly	Endocrine disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Asthenopia	Eye disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Blepharospasm	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Conjunctival irritation	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Eczema eyelids	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Eye pain	Eye disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Hypoaesthesia eye	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Photopsia	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Vision blurred	Eye disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Visual impairment	Eye disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0012 events2 affected172 at risk EG0021 events1 affected136 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Food poisoning	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastroenteritis	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0003 events3 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site dermatitis	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site discolouration	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site discomfort	General disorders	MedDRA	Non-systematic Assessment	EG0006 events6 affected169 at risk EG0013 events3 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site eczema	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site erythema	General disorders	MedDRA	Non-systematic Assessment	EG0004 events3 affected169 at risk EG0019 events7 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site injury	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site irritation	General disorders	MedDRA	Non-systematic Assessment	EG0004 events4 affected169 at risk EG0019 events8 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site pain	General disorders	MedDRA	Non-systematic Assessment	EG0004 events4 affected169 at risk EG00112 events7 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site pruritus	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site rash	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG00114 events13 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site reaction	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site swelling	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Fatigue	General disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Inflammation	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Influenza like illness	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Malaise	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pain	General disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Peripheral swelling	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pyrexia	General disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Hypersensitivity	General disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Application site pustules	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Bacterial infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Conjunctivitis viral	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Cystitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0022 events1 affected136 at risk EG003
Diarrhoea infectious	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Ear infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0014 events4 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0021 events1 affected136 at risk EG003
Gingival abscess	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Herpes virus infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0022 events1 affected136 at risk EG003
Herpes zoster	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Hordeolum	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Infected bite	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Infectious mononucleosis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Influenza	Infections and infestations	MedDRA	Non-systematic Assessment	EG00012 events11 affected169 at risk EG0018 events8 affected172 at risk EG0020 events0 affected136 at risk EG003
Kidney infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Laryngitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0002 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG00022 events22 affected169 at risk EG00110 events10 affected172 at risk EG0023 events3 affected136 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pulpitis dental	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Q fever	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Rectal abscess	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Rhinitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0003 events3 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Scarlet fever	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Tooth abscess	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Viral infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0002 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Foreign body in eye	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0021 events1 affected136 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0013 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Limb fracture	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Muscle injury	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Nerve injury	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Post-traumatic neck syndrome	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Splinter	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Heart rate irregular	Investigations	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0016 events6 affected172 at risk EG0021 events1 affected136 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0012 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Muscle contracture	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0002 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0021 events1 affected136 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0004 events4 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0013 events3 affected172 at risk EG0020 events0 affected136 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0002 events2 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Benign neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Aphasia	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Aura	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Non-systematic Assessment	EG00010 events6 affected169 at risk EG0015 events3 affected172 at risk EG0021 events1 affected136 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0019 events8 affected172 at risk EG0020 events0 affected136 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Headache	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0014 events4 affected172 at risk EG0020 events0 affected136 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Lethargy	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Migraine	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0003 events3 affected169 at risk EG0015 events4 affected172 at risk EG0020 events0 affected136 at risk EG003
Muscle contractions involuntary	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Myoclonus	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0013 events3 affected172 at risk EG0020 events0 affected136 at risk EG003
Phantom pain	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Presyncope	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Status migrainosus	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Syncope	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Affective disorder	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Bruxism	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Depression	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dysphemia	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Insomnia	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Panic attack	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Breast cyst	Reproductive system and breast disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Endometriosis	Reproductive system and breast disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0003 events3 affected169 at risk EG0012 events2 affected172 at risk EG0020 events0 affected136 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0015 events5 affected172 at risk EG0020 events0 affected136 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0006 events6 affected169 at risk EG0016 events6 affected172 at risk EG0020 events0 affected136 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Acne cystic	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0013 events3 affected172 at risk EG0020 events0 affected136 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Skin discomfort	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0014 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Cyst removal	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dental implantation	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Dental operation	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Hernia repair	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Hysterectomy	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Oophorectomy	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Papilloma excision	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Preventive surgery	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Skin lesion excision	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Tooth extraction	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Tooth repair	Surgical and medical procedures	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Hypotension	Vascular disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Labile blood pressure	Vascular disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0021 events1 affected136 at risk EG003
Tooth injury	Injury, poisoning and procedural complications	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003

ID	Term
D051270	Headache Disorders, Primary
D020773	Headache Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Title	Description
BG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
BG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	gammaCore®-R	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).	169	2	169	74	169
EG001	gammaCore®-R Sham	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). gammaCore®-R Sham: Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).	172	1	172	91	172
EG002	Not Randomised	Subjects that were screen failures and were not randomized.	136	0	136	13	136
EG003	Open Label	Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).	277	2	277	118	277

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Admitted because of suspecion of appendicitis	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG0030 events0 affected277 at risk
Basal Cell Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0011 events1 affected172 at risk EG0020 events0 affected136 at risk EG003
Gastric Ulcer	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Migraine attack	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
Surgery for removal cyste and twisted fallopian tube left	Reproductive system and breast disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
carrier BRCA2 gene, prophylactic surgery: adnex extirpation	Congenital, familial and genetic disorders	MedDRA	Non-systematic Assessment	EG0000 events0 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003
obstructive syndrom with dyspnea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 events1 affected169 at risk EG0010 events0 affected172 at risk EG0020 events0 affected136 at risk EG003