Safety and Efficacy Study of Several Replagal Dosing Regi... | NCT00864851

ID	Type	Description	Link
2007-005543-22	EudraCT Number

Label	Type	Description	Intervention Names
Replagal 0.2 mg/kg, IV, every other week	Active Comparator	Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.	Biological: Replagal
Replagal 0.2 mg/kg, IV, weekly	Active Comparator	Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.	Biological: Replagal
Replagal 0.4 mg/kg, IV, weekly	Active Comparator	Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.	Biological: Replagal

Name	Type	Description	Arm Group Labels	Other Names
Replagal	Biological	Intravenous (IV) infusion for 12 months	Replagal 0.2 mg/kg, IV, every other week Replagal 0.2 mg/kg, IV, weekly Replagal 0.4 mg/kg, IV, weekly

Measure	Description	Time Frame
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)	Left ventricular mass (LVM) was measured through echocardiography.	Baseline, Month 12 (Week 53)

Measure	Description	Time Frame
Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise	Exercise tolerance as measured by VO2 max at peak exercise using the standard exponential exercise protocol (STEEP).	Baseline, Month 12 (Week 53)
Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AKDHC Tucson Access Center		Tucson	Arizona	85719	United States
University of Iowa Hospitals and Clinics

PubMed Identifier	Type	Citation	Retractions
20730727	Result	Malek LA, Chojnowska L, Spiewak M, Klopotowski M, Misko J, Petryka J, Milosz B, Ruzyllo W. Cardiac magnetic resonance imaging in patients with Fabry's disease. Kardiol Pol. 2010 Aug;68(8):929-34.

ID	Title	Description
FG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
FG001	Replagal 0.2 mg/kg, IV, Weekly

ID	Title	Description
BG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
BG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
BG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00119 BG0025 BG00344

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)

Left ventricular mass (LVM) was measured through echocardiography.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

g/m^2.7

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts
Participants	OG00015 OG00118 OG0025

Title

Denominators

Categories

Title	Measurements
	OG0003.2± 12.5 OG0010.5± 15.8 OG002-10.3± 11.8

Secondary

Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise

Exercise tolerance as measured by VO2 max at peak exercise using the standard exponential exercise protocol (STEEP).

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

mL/min/kg

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts
Participants

Secondary

Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)

Exercise tolerance using the 6MWT was measured as the total distance walked in 6 minutes.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts
Participants

Secondary

Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score

Quality of life (QoL) was evaluated using the MLHF-Q, version 2. The questionnaire is designed to assess the degree to which heart failure symptoms affect a patient's daily life. The summary score ranges from 0 to 105, with a score of 105 representing the highest adverse impact on a patient's QoL.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

scores on a scale

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Secondary

Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class

The NYHA functional classification system relates symptoms to everyday activities and the patient's quality of life. NYHA Classification - The Stages of Heart Failure: Class I (Mild): No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Class II (Mild): Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea. Class III (Moderate): Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV (Severe): Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Number

participants

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.

Secondary

Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

nmol/ml

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)

Renal function was assessed by an evaluation of change from baseline to Month 12 in eGFR as calculated using the Modification of Diet for Renal Disease (MDRD) equation.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts

Secondary

Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.

Posted

Mean

Standard Deviation

mg/g

Baseline, Month 12 (Week 53)

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Units	Counts
Participants	OG000

Secondary

Safety Evaluation

Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.

Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal. Analyses were performed on the ITT population because it was identical to the safety population.

Posted

Number

participants

56 Weeks

ID	Title	Description
OG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
OG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
OG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
OG003	Overall	Total of all reporting groups.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG00111 events6 affected19 at risk EG0020 events0 affected5 at risk EG00313 events8 affected44 at risk
Bronchitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0013 events3 affected19 at risk EG0021 events1 affected5 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0014 events4 affected19 at risk EG0020 events0 affected5 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0013 events3 affected19 at risk EG0020 events0 affected5 at risk EG003
Viral infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Sinusitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Ear infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Influenza	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Localised infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Meningitis aseptic	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Oral herpes	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Post procedural infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Rhinitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Skin infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Vaginal infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG00013 events5 affected20 at risk EG00113 events7 affected19 at risk EG00213 events1 affected5 at risk EG003
Oedema peripheral	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0015 events4 affected19 at risk EG0023 events1 affected5 at risk EG003
Pyrexia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0004 events3 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Chest pain	General disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0013 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Chest discomfort	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Chills	General disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Catheter site haematoma	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Catheter site swelling	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Feeling cold	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Feeling hot	General disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Implant site paraesthesia	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Implant site reaction	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Inflammation	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Influenza like illness	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Infusion site haematoma	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Malaise	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Pain	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Thirst	General disorders	MedDRA (12.0)	Systematic Assessment	EG0008 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events3 affected20 at risk EG0016 events4 affected19 at risk EG0020 events0 affected5 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0014 events3 affected19 at risk EG0021 events1 affected5 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0015 events5 affected19 at risk EG0020 events0 affected5 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0014 events3 affected19 at risk EG0020 events0 affected5 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0021 events1 affected5 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG00110 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0022 events1 affected5 at risk EG003
Gouty arthritis	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Palpitations	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected19 at risk EG0021 events1 affected5 at risk EG003
Bundle branch block right	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Extrasystoles	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected19 at risk EG0022 events1 affected5 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0021 events1 affected5 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0004 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Atrioventricular block first degree	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Dilatation atrial	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypertrophic cardiomyopathy	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Left ventricular hypertrophy	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events2 affected20 at risk EG0016 events4 affected19 at risk EG0022 events1 affected5 at risk EG003
Dizziness	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0006 events2 affected20 at risk EG0014 events3 affected19 at risk EG0020 events0 affected5 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0023 events2 affected5 at risk EG003
Syncope	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Tremor	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Amnesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Aphasia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Aphonia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Facial paresis	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Hyperreflexia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypoaethesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Lethargy	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0005 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Poor quality sleep	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Sensory loss	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Spastic paralysis	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0004 events2 affected20 at risk EG0019 events3 affected19 at risk EG0020 events0 affected5 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events3 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0013 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Tooth impacted	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0005 events4 affected20 at risk EG0015 events3 affected19 at risk EG0021 events1 affected5 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0021 events1 affected5 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Hyperventilation	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Cardiac murmur	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Haematocrit decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Red blood cell count decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood creatinine phosphokinase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood creatinine increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood glucose increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood iron decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood pressure decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Blood urea increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Body temperature decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Body temperature increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
C-reactive protein increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Electrocardiogram QRS complex prolonged	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Haemoglobin increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Heart rate decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Heart rate irregular	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Mean haemoglobin decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
QRS axis abnormal	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Serum ferritin decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Urinary lipids present	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0013 events3 affected19 at risk EG0020 events0 affected5 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Renal failure chronic	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Renal cyst	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Mouth injury	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Muscle injury	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Tooth injury	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Cervical polyp	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Menopausal symptoms	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0022 events1 affected5 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Rosacea	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Seborrhoea	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Skin tightness	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypotension	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0022 events1 affected5 at risk EG003
Hypertension	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0021 events1 affected5 at risk EG003
Aortic stenosis	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Haematoma	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Hot flush	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Pallor	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Peripheral coldness	Vascular disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Impaired fasting glucose	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Depression	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Alcohol abuse	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Disorientation	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected19 at risk EG0020 events0 affected5 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Vision blurred	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Blindness	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Eye pain	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003
Photophobia	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Biliary dilataton	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Liver injury	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected19 at risk EG0020 events0 affected5 at risk EG003
Myocardial bridging	Congenital, familial and genetic disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected19 at risk EG0020 events0 affected5 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected19 at risk EG0021 events1 affected5 at risk EG003

ID	Term
D013106	Sphingolipidoses
D020140	Lysosomal Storage Diseases, Nervous System
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D059345	Cerebral Small Vessel Diseases
D002561	Cerebrovascular Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008661	Metabolism, Inborn Errors
D008064	Lipidoses
D008052	Lipid Metabolism, Inborn Errors
D016464	Lysosomal Storage Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D052439	Lipid Metabolism Disorders

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Replagal 0.2 mg/kg, IV, Every Other Week	Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.	8	20	19	20
EG001	Replagal 0.2 mg/kg, IV, Weekly	Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.	5	19	17	19
EG002	Replagal 0.4 mg/kg, IV, Weekly	Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.	2	5	5	5
EG003	Overall	Total of all reporting groups.	15	44	41	44