Efficacy and Safety of Fingolimod (FTY720) in Patients Wi... | NCT00355134

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fingolimod 1.25 mg	Experimental	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally once a day. Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.	Drug: Fingolimod
Fingolimod 0.5 mg	Experimental	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.	Drug: Fingolimod
Placebo	Experimental	Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Fingolimod	Drug	Fingolimod capsules for oral administration	Fingolimod 0.5 mg Fingolimod 1.25 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24	ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist). ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).	24 months

Secondary Outcomes

Measure	Description	Time Frame
Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study	ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist). ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama Birmingham		Birmingham	Alabama	35249	United States
North Central Neurology Associates, PC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36286605	Derived	Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, Zhou L, Lu C, Xiao Y, Lu J, Zhao C, Wang M, Wu X, Wu M, Dong Q, Ngew KY, Quan C. Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study. Eur J Neurol. 2023 Feb;30(2):443-452. doi: 10.1111/ene.15612. Epub 2022 Nov 15.
27733070

Label	URL
Fingolimod clinical trials information website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
BG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
BG002	Placebo (Core)	Participants received placebo capsules orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.
BG003	Extension: Fingolimod 1.25 mg	Participants who had received placebo in the Core phase and then received 1.25 mg fingolimod orally once a day in the Extension phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
BG004	Extension: Fingolimod 0.5 mg	Participants who had received placebo in the Core phase and then received 0.5 mg fingolimod orally once a day in the Extension phase.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Demographic data for the Core phase participant population.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00040.9± 8.90 BG00140.6± 8.39 BG00240.1± 8.42 BG003

Age Continuous

Demographic data for the Extension phase population. The number of participants in each treatment group in the Extension phase was 203, 217, 0, 105 and 107; Total participants 632.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00040.6± 8.71 BG001

Gender

Demographic data for the Core phase participant population.

Number

participants

Title

Denominators

Categories

Female

Title	Measurements
	BG000281 BG001275 BG002

Gender

Demographic data for the Extension phase population. The number of participants in each treatment group in the Extension phase was 203, 217, 0, 105 and 107; Total participants 632.

Number

participants

Title

Denominators

Categories

Female

Title	Measurements
	BG000148 BG001160

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

Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24

ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.

A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).

ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).

Full analysis set, including all patients who were randomized and took at least one dose of study drug.

Posted

Number

95% Confidence Interval

relapses per year

24 months

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002	Placebo	Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

Units	Counts
Participants	OG000370 OG001358 OG002355

Title

Denominators

Categories

Title	Measurements
	OG0000.203(0.165 to 0.249) OG0010.208(0.170 to 0.254) OG0020.403(0.342 to 0.475)

Secondary

Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.

Posted

Number

95% Confidence Interval

relapses per year

From Baseline until end of study (up to approximately 54 months).

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.

Secondary

Percent Change From Baseline in Brain Volume

Brain volume was measured using magnetic resonance imaging (MRI). Change from Baseline in brain volume is expressed as a percentage of the Baseline brain volume.

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. Patients were grouped according to the assigned treatment. "N" indicates the number of participants with data available for the specified time period.

Posted

Mean

Standard Deviation

percent change

Baseline, Month 24 and end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002	Placebo

Secondary

Number of New or Newly Enlarged T2 Lesions

Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions, by year.

Posted

Mean

Standard Deviation

lesions

From Baseline until Month 48

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002	Placebo	Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

Secondary

Number of Gadolinium-enhanced T1 Lesions

Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions.

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug. "N" indicates the number of participants with evaluable MRI data for the specified time point.

Posted

Mean

Standard Deviation

lesions

Month 24 and end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002	Placebo	Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

Secondary

Change From Baseline in Lesion Volume at Month 24 (Core Phase)

Change from Baseline in lesion volume was measured by MRI for T2 lesions and for T1 hypointense lesions.

Full analysis set for whom data were available. N=the number of patients with non-missing baseline and post-baseline values.

Posted

Mean

Standard Deviation

mm^3

Baseline and Month 24

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002	Placebo	Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

Secondary

Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study

Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression was defined as a 3-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.

Posted

Number

95% Confidence Interval

percentage of participants

24 months and end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.

Secondary

Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study

Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined as a 6-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.

Posted

Number

95% Confidence Interval

percentage of participants

24 months and end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.

Secondary

Percentage of Participants Relapse-free up to Month 24

Estimates of the percentage of participants relapse-free at 24 months were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.

Full analysis set

Posted

Number

95% Confidence Interval

percentage of participants

24 months

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
OG002

Secondary

Percentage of Participants Relapse-free up to End of Study

Estimates of the percentage of participants relapse-free at end of study were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.

Core intent-to-treat (ITT) population: All patients who were randomized in the Core phase and received at least one dose of Core phase drug.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until the end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.

Secondary

Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score

The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Month 24 and end of study (up to approximately 54 months)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.
OG001	Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Core: Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.	53	370	335	370
EG001	Core: Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase.	53	358	320	358
EG002	Core: Placebo	Participants received placebo capsules orally once a day for up to 24 months during the core phase. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.	45	355	305	355
EG003	Extension: Fingolimod 1.25 mg	Participants received 1.25 mg fingolimod orally once a day in the Extension phase. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.	27	308	216	308
EG004	Extension: Fingolimod 0.5 mg	Participants received 0.5 mg fingolimod orally once a day in the Extension phase.	21	324	223	324

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Idiopathic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG0030 affected308 at risk EG004
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0022 affected355 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Atrioventricular block first degree	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0006 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Cardiac flutter	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Mitral valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Pericarditis	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Diabetes insipidus	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Macular oedema	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Retinal detachment	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Abdominal mass	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0012 affected358 at risk EG0022 affected355 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Caecitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Gastric disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Chest discomfort	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0012 affected358 at risk EG0020 affected355 at risk EG003
Pelvic mass	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0022 affected355 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Acute sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0012 affected358 at risk EG0021 affected355 at risk EG003
Bartholin's abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Encephalitis herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Gastritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Hepatitis C	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Herpes zoster disseminated	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Kidney infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Labyrinthitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Lower respiratory tract infection fungal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Lyme disease	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Mastoiditis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Post procedural infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0012 affected358 at risk EG0020 affected355 at risk EG003
Staphylococcal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Vulvitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Drug exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Morphoea	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Astrocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0006 affected370 at risk EG0019 affected358 at risk EG0022 affected355 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Dysplastic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Ependymoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Hair follicle tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Sarcoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0003 affected370 at risk EG0011 affected358 at risk EG0022 affected355 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
T-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Thyroid adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0022 affected355 at risk EG003
Akathisia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0013 affected358 at risk EG0021 affected355 at risk EG003
Encephalitis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0021 affected355 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Grand mal convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Intracranial aneurysm	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0011 affected358 at risk EG0022 affected355 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0011 affected358 at risk EG0023 affected355 at risk EG003
Optic neuritis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Sciatica	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Simple partial seizures	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Status epilepticus	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected370 at risk EG0012 affected358 at risk EG0021 affected355 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Abortion	Pregnancy, puerperium and perinatal conditions	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Acute psychosis	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Aggression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0022 affected355 at risk EG003
Drug dependence	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Frustration	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Hallucination	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Major depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0023 affected355 at risk EG003
Mania	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Mental disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0022 affected355 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Paranoia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Suicidal behaviour	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0013 affected358 at risk EG0020 affected355 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Adenomyosis	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Cervical cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Cervical dysplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Cystocele	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Haemorrhagic ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Menorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Rectocele	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0022 affected355 at risk EG003
Uterovaginal prolapse	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0011 affected358 at risk EG0020 affected355 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Abortion induced	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Aortic dissection	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0021 affected355 at risk EG003
Embolism	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Haemorrhage	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected370 at risk EG0010 affected358 at risk EG0020 affected355 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00036 affected370 at risk EG00126 affected358 at risk EG0020 affected355 at risk EG00325 affected308 at risk EG00419 affected324 at risk
Vision blurred	Eye disorders	MedDRA	Systematic Assessment	EG0008 affected370 at risk EG00118 affected358 at risk EG00212 affected355 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected370 at risk EG00118 affected358 at risk EG0027 affected355 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00052 affected370 at risk EG00148 affected358 at risk EG00243 affected355 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00018 affected370 at risk EG00112 affected358 at risk EG00218 affected355 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00057 affected370 at risk EG00163 affected358 at risk EG00254 affected355 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00029 affected370 at risk EG00121 affected358 at risk EG00227 affected355 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00029 affected370 at risk EG00122 affected358 at risk EG00225 affected355 at risk EG003
Pain	General disorders	MedDRA	Systematic Assessment	EG00021 affected370 at risk EG00110 affected358 at risk EG00215 affected355 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG00016 affected370 at risk EG00114 affected358 at risk EG00220 affected355 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG00034 affected370 at risk EG00129 affected358 at risk EG00220 affected355 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG00026 affected370 at risk EG00134 affected358 at risk EG00224 affected355 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00088 affected370 at risk EG00184 affected358 at risk EG00285 affected355 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG00045 affected370 at risk EG00155 affected358 at risk EG00245 affected355 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00092 affected370 at risk EG00187 affected358 at risk EG00286 affected355 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00045 affected370 at risk EG00147 affected358 at risk EG00254 affected355 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG00016 affected370 at risk EG00122 affected358 at risk EG00216 affected355 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG00035 affected370 at risk EG00129 affected358 at risk EG0026 affected355 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment	EG00021 affected370 at risk EG00123 affected358 at risk EG0022 affected355 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA	Systematic Assessment	EG00020 affected370 at risk EG00113 affected358 at risk EG0020 affected355 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00036 affected370 at risk EG00130 affected358 at risk EG00238 affected355 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00034 affected370 at risk EG00129 affected358 at risk EG00239 affected355 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00021 affected370 at risk EG00114 affected358 at risk EG00216 affected355 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00036 affected370 at risk EG00144 affected358 at risk EG00227 affected355 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG00033 affected370 at risk EG00138 affected358 at risk EG00244 affected355 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG00053 affected370 at risk EG00138 affected358 at risk EG00243 affected355 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00081 affected370 at risk EG00183 affected358 at risk EG00276 affected355 at risk EG003
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG00015 affected370 at risk EG00124 affected358 at risk EG00219 affected355 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG00014 affected370 at risk EG00119 affected358 at risk EG00218 affected355 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG00018 affected370 at risk EG00118 affected358 at risk EG00217 affected355 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG00034 affected370 at risk EG00129 affected358 at risk EG00232 affected355 at risk EG003
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG00024 affected370 at risk EG00131 affected358 at risk EG00224 affected355 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00051 affected370 at risk EG00152 affected358 at risk EG00253 affected355 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00046 affected370 at risk EG00134 affected358 at risk EG00233 affected355 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00023 affected370 at risk EG00117 affected358 at risk EG00221 affected355 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00025 affected370 at risk EG00129 affected358 at risk EG00232 affected355 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00021 affected370 at risk EG00122 affected358 at risk EG00224 affected355 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG00046 affected370 at risk EG00132 affected358 at risk EG00211 affected355 at risk EG003

Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D013110	Sphingosine
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D011409	Propylene Glycols
D006018	Glycols
D000588	Amines

ID	Term
D009103	Multiple Sclerosis
D020529	Multiple Sclerosis, Relapsing-Remitting