Efficacy and Safety of Fingolimod in Patients With Relaps... | NCT00289978

NCT00289978

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Intervention Names
Fingolimod 1.25 mg	Experimental	Drug: Fingolimod 1.25 mg
Fingolimod 0.5 mg	Experimental	Drug: Fingolimod 0.5 mg
Placebo	Placebo Comparator	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Fingolimod 1.25 mg	Drug	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Fingolimod 1.25 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Estimated Annualized Aggregate Relapse Rate (ARR)	The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25.	Baseline to end of study (Month 24)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)	EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
The Queen Elizabeth Hospital		Woodville South	South Australia	5011	Australia
North Gosford Private Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35698787	Derived	Nowak CP, Mutze T, Konietschke F. Group sequential methods for the Mann-Whitney parameter. Stat Methods Med Res. 2022 Oct;31(10):2004-2020. doi: 10.1177/09622802221107103. Epub 2022 Jun 13.
27733070	Derived	Fox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.

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	Patients self-administered fingolimod 1.25 mg capsules orally once daily.
FG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Fingolimod 1.25 mg	Patients self-administered fingolimod 1.25 mg capsules orally once daily.
BG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.
BG002	Placebo	Patients self-administered a fingolimod placebo capsule orally once daily.
BG003	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

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00037.4± 8.91 BG00136.6± 8.77 BG00237.2± 8.60 BG003

Age, Customized

Number

participants

Title

Denominators

Categories

<18 years

Title	Measurements
	BG0001 BG0010 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000295 BG001296 BG002

Duration of multiple sclerosis since first symptoms

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG0008.4± 6.86(0 to 37) BG0018.0± 6.60(0 to 35) BG002

Number of relapses in last 2 years

Mean

Standard Deviation

relapses

Title

Denominators

Categories

Title	Measurements
	BG0001.5± 0.81(1 to 10) BG0011.5± 0.76(1 to 11) BG002

Expanded Disability Status Scale (EDSS)

The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). Based on scores in these 8 functional systems, an overall score ranging from 0 (normal) to 10 (death due to MS) is assigned. Patients with EDSS scores of 0.0 to 4.5 are fully ambulatory; patients with EDSS scores of 5.0 to 9.5 have impaired ambulation. EDSS was assessed by an evaluating physician at each site.

Mean

Standard Deviation

Units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0002.41± 1.36(0 to 5.5) BG001

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

Estimated Annualized Aggregate Relapse Rate (ARR)

The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25.

This analysis was conducted using the Intent-to-treat (ITT) population which includes all patients who were randomized and received at least one dose of study drug.

Posted

Number

95% Confidence Interval

Relapses per year

Baseline to end of study (Month 24)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Patients self-administered fingolimod 1.25 mg capsules orally once daily.
OG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.
OG002	Placebo	Patients self-administered a fingolimod placebo capsule orally once daily.

Units	Counts
Participants	OG000429 OG001425 OG002418

Title

Denominators

Categories

Title	Measurements
	OG0000.16(0.13 to 0.19) OG0010.18(0.15 to 0.22) OG0020.40(0.34 to 0.47)

Secondary

Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method.

Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline to end of study (Month 24)

ID	Title	Description
OG000	Fingolimod 1.25 mg	Patients self-administered fingolimod 1.25 mg capsules orally once daily.
OG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.
OG002	Placebo	Patients self-administered a fingolimod placebo capsule orally once daily.

Secondary

Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline

The number of new or newly enlarged T2 lesions at Month 24 in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.

Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

Posted

Mean

Standard Deviation

T2 lesions

Baseline to end of study (Month 24)

patients with non-missing values

Participants

ID	Title	Description
OG000	Fingolimod 1.25 mg	Patients self-administered fingolimod 1.25 mg capsules orally once daily.
OG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.
OG002	Placebo	Patients self-administered a fingolimod placebo capsule orally once daily.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fingolimod 1.25 mg	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	51	429	346	429
EG001	Fingolimod 0.5 mg	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	43	425	355	425
EG002	Placebo	Patients self-administered a fingolimod placebo capsule orally once daily.	56	418	323	418

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Angina pectoris	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Bradycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0003 affected429 at risk EG0014 affected425 at risk EG0021 affected418 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0022 affected418 at risk
Palpitations	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Pericarditis	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Tachycardia paroxysmal	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Eye pain	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Iridocyclitis	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Keratitis	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Macular oedema	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0003 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Papilloedema	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Photopsia	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Retinal detachment	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Retinal disorder	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Retinitis	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Gastritis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Chest pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0012 affected425 at risk EG0020 affected418 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Haemorrhagic cyst	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Inflammation	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Non-cardiac chest pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0012 affected425 at risk EG0022 affected418 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Cytolytic hepatitis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Abscess jaw	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Acute sinusitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Anal abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Appendicitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Clostridial infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Cystitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Dermo-hypodermitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Gastroenteritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Genital herpes	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Herpes virus infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Mastoiditis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Otitis media acute	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Peritoneal abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Peritonsillitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Pharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Pyelonephritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Pyelonephritis chronic	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Sinusitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Streptococcal abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Tonsillitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Tooth abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0012 affected425 at risk EG0020 affected418 at risk
Urosepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Burns second degree	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Fractured coccyx	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Splenic injury	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Splenic rupture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Electrocardiogram PR prolongation	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Electrocardiogram change	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Hepatic enzyme increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Liver function test abnormal	Investigations	MedDRA 12.0	Systematic Assessment	EG0002 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Precancerous cells present	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Red blood cell sedimentation rate increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0012 affected425 at risk EG0021 affected418 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0022 affected418 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0014 affected425 at risk EG0022 affected418 at risk
Benign ovarian tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Brain neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0023 affected418 at risk
Cervix carcinoma stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Ovarian adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Amnesia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Central nervous system lesion	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Epilepsy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Grand mal convulsion	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Migraine with aura	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Monoplegia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Multiple sclerosis	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0012 affected425 at risk EG0020 affected418 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 affected429 at risk EG0012 affected425 at risk EG0021 affected418 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Presyncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Sciatica	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Somnolence	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Syncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0021 affected418 at risk
Abortion	Pregnancy, puerperium and perinatal conditions	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0023 affected418 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Acute psychosis	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Anxiety	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Depression	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Homicidal ideation	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Renal colic	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Renal cyst	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Ovarian disorder	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected429 at risk EG0010 affected425 at risk EG0020 affected418 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Circulatory collapse	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0010 affected425 at risk EG0021 affected418 at risk
Varicose vein	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected429 at risk EG0011 affected425 at risk EG0020 affected418 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 12.0	Systematic Assessment	EG00018 affected429 at risk EG00118 affected425 at risk EG00221 affected418 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00040 affected429 at risk EG00150 affected425 at risk EG00230 affected418 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00038 affected429 at risk EG00138 affected425 at risk EG00236 affected418 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG00046 affected429 at risk EG00148 affected425 at risk EG00245 affected418 at risk
Bronchitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00039 affected429 at risk EG00134 affected425 at risk EG00215 affected418 at risk
Influenza	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00040 affected429 at risk EG00155 affected425 at risk EG00241 affected418 at risk
Nasopharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG000112 affected429 at risk EG001115 affected425 at risk EG002115 affected418 at risk
Pharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00025 affected429 at risk EG00126 affected425 at risk EG00223 affected418 at risk
Rhinitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00018 affected429 at risk EG00125 affected425 at risk EG00225 affected418 at risk
Sinusitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00027 affected429 at risk EG00127 affected425 at risk EG00219 affected418 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00062 affected429 at risk EG00173 affected425 at risk EG00272 affected418 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00021 affected429 at risk EG00134 affected425 at risk EG00247 affected418 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG00049 affected429 at risk EG00142 affected425 at risk EG00216 affected418 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG00031 affected429 at risk EG00122 affected425 at risk EG0024 affected418 at risk
Weight increased	Investigations	MedDRA 12.0	Systematic Assessment	EG00014 affected429 at risk EG00114 affected425 at risk EG00222 affected418 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00026 affected429 at risk EG00124 affected425 at risk EG00226 affected418 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00026 affected429 at risk EG00130 affected425 at risk EG00233 affected418 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00045 affected429 at risk EG00149 affected425 at risk EG00228 affected418 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00024 affected429 at risk EG00128 affected425 at risk EG00227 affected418 at risk
Dizziness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00031 affected429 at risk EG00131 affected425 at risk EG00223 affected418 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG000113 affected429 at risk EG001107 affected425 at risk EG00296 affected418 at risk
Paraesthesia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00017 affected429 at risk EG00123 affected425 at risk EG00218 affected418 at risk
Depression	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG00025 affected429 at risk EG00133 affected425 at risk EG00228 affected418 at risk
Insomnia	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG00016 affected429 at risk EG00121 affected425 at risk EG00225 affected418 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00037 affected429 at risk EG00143 affected425 at risk EG00234 affected418 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00025 affected429 at risk EG00130 affected425 at risk EG00219 affected418 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00017 affected429 at risk EG00129 affected425 at risk EG00229 affected418 at risk
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG00027 affected429 at risk EG00126 affected425 at risk EG00215 affected418 at risk

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

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