A Phase II Study Comparing Low- and High-Dose Alemtuzumab... | NCT00050778

Name	Class
Bayer	INDUSTRY

Label	Type	Intervention Names
Interferon Beta-1a	Active Comparator	Biological: Interferon beta-1a
Alemtuzumab 12 mg	Experimental	Biological: Alemtuzumab 12 mg
Alemtuzumab 24 mg	Experimental	Biological: Alemtuzumab 24 mg

Name	Type	Description	Arm Group Labels	Other Names
Interferon beta-1a	Biological	Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 36 months.	Interferon Beta-1a

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Probability of Participants With Sustained Accumulation of Disability (SAD)	EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.	Up to 3 years
Annualized Relapse Rate	Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.	Up to 3 years

Secondary Outcomes

Measure	Description	Time Frame
Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment	Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent form (ICF)
Male or non-pregnant, non-lactating female participants, 18 to 50 years of age (inclusive) as of signing the ICF
Diagnosis of MS per McDonald's update of the Poser criteria, including cranial MRI consistent with those criteria (McDonald, 2001, Ann Neurol)
Onset of first MS symptoms within 3 years prior to Screening as of signing the ICF
Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at the screening and Baseline visits
At least 2 completed clinical episodes of MS in the 2 years prior to study entry (that is, the initial event if within 2 years of study entry plus at least 1 relapse, or at least 2 relapses if the initial event was between 2 and 3 years prior to study entry)
In addition to the clinical criteria, at least 1 enhancing lesion on any 1 of up to 4 screening gadolinium-enhanced MRI brain scans during a maximum 3-month run-in period (inclusive of the Month 0 Baseline scan)

Exclusion Criteria:

Previous immunotherapy for MS other than steroids, including treatment with interferons, intravenous immunoglobulin (IVIG), glatiramer acetate, and mitoxantrone
Personal history of thyroid autoimmune disease
Personal history of clinically significant autoimmune disease (for example, inflammatory bowel disease, diabetes, lupus, severe asthma)
History of thyroid carcinoma (previous thyroid adenoma was acceptable and was not considered an exclusion criterion)
History of malignancy (except for basal cell skin carcinoma if disease-free for at least 5 years)
Any disability acquired from trauma or another illness that, in the opinion of the Investigator, interfered with evaluation of disability due to MS
Previous treatment with alemtuzumab
History of anaphylaxis following exposure to humanized monoclonal antibodies
Inability to undergo MRI with gadolinium administration
Female participants of childbearing potential with a positive serum pregnancy test at screening or Baseline
Male and female participants who did not agree to use effective contraceptive method(s) during the study
Impaired renal function (that is, serum creatinine greater than or equal to 2 times the upper limit of normal [ULN])
Untreated, major depressive disorder
Epileptic seizures that were not adequately controlled by treatment
Suicidal ideation
Major systemic disease or other illness that, in the opinion of the Investigator, have compromised participant safety or interfered with the interpretation of study results
Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-thyroid stimulating hormone (TSH) receptor antibodies; known seropositivity for human immunodeficiency (HIV)
Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
Presence of a monoclonal paraprotein
Participants who had any form of MS other than relapsing-remitting
Participants currently participating in a clinical study of an experimental or unapproved/unlicensed therapy

Name	Affiliation	Role
Medical Monitor	Genzyme, a Sanofi Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale Arizona		Scottsdale	Arizona	85259	United States
Clinical Trials, Inc

PubMed Identifier	Type	Citation	Retractions
16044212	Background	Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. doi: 10.1007/s00415-005-0934-5. Epub 2005 Jul 27.
18946064	Result

ID	Title	Description
FG000	Interferon Beta-1a	Interferon beta-1a (Rebif®) 44 micrograms (mcg) subcutaneously 3-times weekly for 36 months.
FG001	Alemtuzumab 12 mg	Alemtuzumab (Lemtrada™) 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ [CD4+] T-cell count was >=100*10^6 cells per liter).

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
	BG00032.8± 8.82 BG00131.9± 8.01 BG00232.2± 8.76 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00071 BG00172 BG002

Time Since First Relapse

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG0001.4(0.2 to 6.3) BG0011.3(0.1 to 3.5) BG002

Number of Relapse Episodes in the Preceding 2 Years

Number of participants with 0, 1, 2 or greater than or equal to 3 relapses are reported.

Number

participants

Title

Denominators

Categories

0 Relapse

Title	Measurements
	BG0000 BG0012 BG002

Total Number of Relapses

Number

relapses

Title

Denominators

Categories

Title	Measurements
	BG000293 BG001301 BG002

Expanded Disability Status Scale (EDSS) Score

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Number of participants evaluable for this Baseline characteristic were 110, 112 and 110 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0001.9± 0.81 BG001

Time Constant 1 (T1) Cerebral Volume

Number of participants evaluable for this Baseline characteristic were 103, 107 and 107 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively. Partial brain volumes were measured using the technique of Losseff et al. (1996).

Mean

Standard Deviation

cubic centimeter

Title

Denominators

Categories

Title	Measurements
	BG000317.5± 24.70 BG001

Time Constant 2 (T2) Lesion Volume

Number of participants evaluable for this Baseline characteristic were 102, 106 and 107 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively.

Mean

Standard Deviation

cubic centimeter

Title

Denominators

Categories

Title	Measurements
	BG00015.8± 15.23 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

Probability of Participants With Sustained Accumulation of Disability (SAD)

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.

Full Analysis Set (FAS) population included all randomized participants who had correct diagnosis of MS at entry.

Posted

Number

95% Confidence Interval

probability of participants with SAD

Up to 3 years

ID	Title	Description
OG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
OG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG003	Alemtuzumab (Pooled)	Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).

Units	Counts
Participants	OG000111 OG001112 OG002110 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.27(0.193 to 0.380) OG0010.08(0.043 to 0.165) OG0020.09(0.052 to 0.169) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Cox proportional hazards (PH) regression model using treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country) as covariates was used.	Cox Proportional Hazards Regression		0.0006	An alpha-sharing approach was used to adjust for multiple treatment group comparisons, endpoints, and two pre-planned interim analyses, including a Lan-Demets error-spending function. Pre-specified threshold for statistical significance was 0.0165.	Hazard Ratio (HR)	0.24			2-Sided	95	0.110	0.545				No	Superiority or Other

Primary

Annualized Relapse Rate

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.

FAS population included all randomized participants who had correct diagnosis of MS at entry.

Posted

Number

95% Confidence Interval

relapses per participant per year

Up to 3 years

ID	Title	Description
OG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
OG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG002	Alemtuzumab 24 mg

Secondary

Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment

Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.

FAS population included all randomized participants who had correct diagnosis of MS at entry.

Posted

Number

95% Confidence Interval

probability of participants

Year 3

ID	Title	Description
OG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
OG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).

Secondary

Percent Change From Baseline in T1 Cerebral Volume at Year 3

Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100*([brain volume at Year 3] minus [brain volume at Baseline]) divided by [brain volume at Baseline]).

Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T1 brain volume at Baseline and Year 3.

Posted

Mean

Standard Deviation

percent change

Baseline, Year 3

ID	Title	Description
OG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
OG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).

Secondary

Percent Change From Baseline in MRI T2 Lesion Volume at Year 3

Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100*([lesion volume at Year 3] minus [lesion volume at Baseline]) divided by [lesion volume at Baseline]).

Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T2 lesion volume at Baseline and Year 3.

Posted

Mean

Standard Deviation

percent change

Baseline, Year 3

ID	Title	Description
OG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
OG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
OG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Autoimmune thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0021 affected108 at risk EG0032 affected216 at risk
Idiopathic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Cardiovascular disorder	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Autoimmune thyroiditis	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Basedow's disease	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Thyroiditis subacute	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Cataract	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Diplopia	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Exophthalmos	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Vision blurred	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Enterocutaneous fistula	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Erosive oesophagitis	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Gastroduodenitis	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Ileus paralytic	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Peritonitis	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Salivary gland calculus	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Adverse drug reaction	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Asthenia	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Chest discomfort	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Death	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Fatigue	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Gait disturbance	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Infusion related reaction	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Pyrexia	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Appendicitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Bronchitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Catheter bacteraemia	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Cellulitis of male external genital organ	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Cervicitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0021 affected108 at risk EG003
Herpes ophthalmic	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Meningitis listeria	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Meningitis viral	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Sepsis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Sinusitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Varicella	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Viral infection	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Limb traumatic amputation	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Traumatic brain injury	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Traumatic lung injury	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Transaminases increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0002 affected107 at risk EG0012 affected108 at risk EG0021 affected108 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Acoustic neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Angiomyolipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Glomus tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Ataxia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0002 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Carpal tunnel syndrome	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Cerebellar ataxia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Dizziness	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Headache	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0021 affected108 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00014 affected107 at risk EG0015 affected108 at risk EG0029 affected108 at risk EG003
Myelitis	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Paraparesis	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Paresis	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Sensory disturbance	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Sensory loss	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Syncope	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Abortion	Pregnancy, puerperium and perinatal conditions	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Abortion missed	Pregnancy, puerperium and perinatal conditions	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0021 affected108 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Abortion threatened	Pregnancy, puerperium and perinatal conditions	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Bipolar disorder	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Goodpasture's syndrome	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Ectropion of cervix	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Endometriosis	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Menometrorrhagia	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Menorrhagia	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Ovarian cyst ruptured	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Ovarian disorder	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0021 affected108 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Hypertension	Vascular disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Hypotension	Vascular disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0016 affected108 at risk EG0024 affected108 at risk EG00310 affected216 at risk
Palpitations	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG0016 affected108 at risk EG0028 affected108 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG00113 affected108 at risk EG00213 affected108 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 12.1	Non-systematic Assessment	EG00010 affected107 at risk EG00112 affected108 at risk EG00211 affected108 at risk EG003
Basedow's disease	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG00112 affected108 at risk EG0026 affected108 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG00111 affected108 at risk EG00213 affected108 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG00111 affected108 at risk EG00211 affected108 at risk EG003
Diplopia	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0007 affected107 at risk EG0013 affected108 at risk EG0026 affected108 at risk EG003
Vision blurred	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG0019 affected108 at risk EG00216 affected108 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0014 affected108 at risk EG0022 affected108 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0007 affected107 at risk EG0016 affected108 at risk EG0025 affected108 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0012 affected108 at risk EG0024 affected108 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG0019 affected108 at risk EG0026 affected108 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0007 affected107 at risk EG00117 affected108 at risk EG00217 affected108 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00116 affected108 at risk EG00213 affected108 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0016 affected108 at risk EG0027 affected108 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG00017 affected107 at risk EG00132 affected108 at risk EG00245 affected108 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0012 affected108 at risk EG0029 affected108 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0011 affected108 at risk EG0026 affected108 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00118 affected108 at risk EG00219 affected108 at risk EG003
Asthenia	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG00118 affected108 at risk EG00212 affected108 at risk EG003
Chest discomfort	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG00112 affected108 at risk EG00218 affected108 at risk EG003
Chills	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0008 affected107 at risk EG00119 affected108 at risk EG00221 affected108 at risk EG003
Fatigue	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00031 affected107 at risk EG00147 affected108 at risk EG00244 affected108 at risk EG003
Gait disturbance	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00013 affected107 at risk EG0016 affected108 at risk EG0025 affected108 at risk EG003
Hyperthermia	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0017 affected108 at risk EG0025 affected108 at risk EG003
Influenza like illness	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00032 affected107 at risk EG00121 affected108 at risk EG00215 affected108 at risk EG003
Injection site erythema	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00035 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Injection site pain	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00018 affected107 at risk EG0013 affected108 at risk EG0020 affected108 at risk EG003
Injection site reaction	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00012 affected107 at risk EG0011 affected108 at risk EG0020 affected108 at risk EG003
Oedema peripheral	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG0016 affected108 at risk EG0023 affected108 at risk EG003
Pain	General disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG00113 affected108 at risk EG00214 affected108 at risk EG003
Pyrexia	General disorders	MedDRA 12.1	Non-systematic Assessment	EG00011 affected107 at risk EG00147 affected108 at risk EG00247 affected108 at risk EG003
Bronchitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG00111 affected108 at risk EG00214 affected108 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0014 affected108 at risk EG0028 affected108 at risk EG003
Influenza	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG00110 affected108 at risk EG0023 affected108 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG00014 affected107 at risk EG00117 affected108 at risk EG00226 affected108 at risk EG003
Oral herpes	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0017 affected108 at risk EG0028 affected108 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG0013 affected108 at risk EG0029 affected108 at risk EG003
Rhinitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG0019 affected108 at risk EG0029 affected108 at risk EG003
Sinusitis	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00113 affected108 at risk EG00218 affected108 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG00010 affected107 at risk EG00121 affected108 at risk EG00228 affected108 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG00011 affected107 at risk EG00111 affected108 at risk EG00217 affected108 at risk EG003
Viral infection	Infections and infestations	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0014 affected108 at risk EG0022 affected108 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG0016 affected108 at risk EG00215 affected108 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0010 affected108 at risk EG0020 affected108 at risk EG003
Body temperature increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0011 affected108 at risk EG0026 affected108 at risk EG003
Weight decreased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0002 affected107 at risk EG0017 affected108 at risk EG0029 affected108 at risk EG003
Weight increased	Investigations	MedDRA 12.1	Non-systematic Assessment	EG0007 affected107 at risk EG0019 affected108 at risk EG00211 affected108 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG00010 affected107 at risk EG00121 affected108 at risk EG00211 affected108 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG00011 affected107 at risk EG00117 affected108 at risk EG00227 affected108 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG00011 affected107 at risk EG00119 affected108 at risk EG00220 affected108 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0017 affected108 at risk EG0022 affected108 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG00030 affected107 at risk EG00117 affected108 at risk EG00220 affected108 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00110 affected108 at risk EG0025 affected108 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00111 affected108 at risk EG00212 affected108 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG0018 affected108 at risk EG0027 affected108 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG00016 affected107 at risk EG00125 affected108 at risk EG00232 affected108 at risk EG003
Ataxia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00013 affected107 at risk EG0015 affected108 at risk EG0023 affected108 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG0017 affected108 at risk EG0025 affected108 at risk EG003
Burning sensation	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG0012 affected108 at risk EG0028 affected108 at risk EG003
Coordination abnormal	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0016 affected108 at risk EG0024 affected108 at risk EG003
Dizziness	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00011 affected107 at risk EG00113 affected108 at risk EG00229 affected108 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00022 affected107 at risk EG00118 affected108 at risk EG00219 affected108 at risk EG003
Headache	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00026 affected107 at risk EG00172 affected108 at risk EG00285 affected108 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00024 affected107 at risk EG00129 affected108 at risk EG00226 affected108 at risk EG003
Migraine	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG0019 affected108 at risk EG0026 affected108 at risk EG003
Multiple sclerosis	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG0018 affected108 at risk EG0026 affected108 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00040 affected107 at risk EG00127 affected108 at risk EG00221 affected108 at risk EG003
Muscle spasticity	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0008 affected107 at risk EG0014 affected108 at risk EG0020 affected108 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG00018 affected107 at risk EG00136 affected108 at risk EG00222 affected108 at risk EG003
Sensory disturbance	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0008 affected107 at risk EG0017 affected108 at risk EG0027 affected108 at risk EG003
Tremor	Nervous system disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG0017 affected108 at risk EG0026 affected108 at risk EG003
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 12.1	Non-systematic Assessment	EG0009 affected107 at risk EG00111 affected108 at risk EG0026 affected108 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG00010 affected107 at risk EG00112 affected108 at risk EG00220 affected108 at risk EG003
Depression	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG00020 affected107 at risk EG00119 affected108 at risk EG00218 affected108 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 12.1	Non-systematic Assessment	EG00017 affected107 at risk EG00136 affected108 at risk EG00229 affected108 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0011 affected108 at risk EG0026 affected108 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0014 affected108 at risk EG0026 affected108 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0016 affected108 at risk EG0023 affected108 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG0010 affected108 at risk EG0022 affected108 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG00112 affected108 at risk EG00212 affected108 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG00117 affected108 at risk EG00218 affected108 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0017 affected108 at risk EG0026 affected108 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG00116 affected108 at risk EG00214 affected108 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0001 affected107 at risk EG0016 affected108 at risk EG0027 affected108 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0005 affected107 at risk EG00110 affected108 at risk EG0028 affected108 at risk EG003
Hypoaesthesia facial	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0002 affected107 at risk EG0016 affected108 at risk EG0025 affected108 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0004 affected107 at risk EG00136 affected108 at risk EG00228 affected108 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0008 affected107 at risk EG00178 affected108 at risk EG00282 affected108 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG00113 affected108 at risk EG0027 affected108 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0000 affected107 at risk EG0016 affected108 at risk EG0024 affected108 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12.1	Non-systematic Assessment	EG0003 affected107 at risk EG00131 affected108 at risk EG00238 affected108 at risk EG003
Flushing	Vascular disorders	MedDRA 12.1	Non-systematic Assessment	EG0006 affected107 at risk EG00112 affected108 at risk EG0028 affected108 at risk EG003
Hypertension	Vascular disorders	MedDRA 12.1	Non-systematic Assessment	EG0008 affected107 at risk EG0016 affected108 at risk EG0023 affected108 at risk EG003

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
D016899	Interferon-beta
D007370	Interferon Type I
D007372	Interferons
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Interferon Beta-1a	Interferon beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
BG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
BG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Interferon Beta-1a	Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	29	107	106	107
EG001	Alemtuzumab 12 mg	Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).	30	108	108	108
EG002	Alemtuzumab 24 mg	Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).	33	108	108	108
EG003	Alemtuzumab (Pooled)	Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).	63	216	216	216