Efficacy and Safety Study of ISIS 301012 (Mipomersen) as... | NCT00706849

Name	Class
Ionis Pharmaceuticals, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Mipomersen	Experimental	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.	Drug: mipomersen sodium
Placebo	Placebo Comparator	Participants received a placebo subcutaneous injection once a week for 26 weeks.	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
mipomersen sodium	Drug	200 mg /mL	Mipomersen	ISIS 301012

Measure	Description	Time Frame
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point	LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
LDL Cholesterol at Baseline and at the Primary Efficacy Time Point	The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

Measure	Description	Time Frame
Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point	Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

Measure	Description	Time Frame
Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point	Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

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

Facility	Status	City	State	ZIP	Country	Contacts
		La Jolla	California	92093	United States

PubMed Identifier	Type	Citation	Retractions
23060426	Result	Stein EA, Dufour R, Gagne C, Gaudet D, East C, Donovan JM, Chin W, Tribble DL, McGowan M. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation. 2012 Nov 6;126(19):2283-92. doi: 10.1161/CIRCULATIONAHA.112.104125. Epub 2012 Oct 11.
27578134

ID	Title	Description
FG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
FG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

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

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point

LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.

Posted

Mean

Standard Deviation

percentage of Baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG00041 OG00182

Title

Denominators

Categories

Title	Measurements
	OG0005.17± 18.02 OG001-28.02± 26.99

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	Based upon prior clinical study experience with mipomersen, it was estimated that the standard deviation of the percent change in LDL-C is approximately 22%. With 20 patients in the control group and 40 patients in the mipomersen-treated group, this study would have at least 90% power to detect a 20% difference between the 2 treatment groups.	t-test, 2 sided		<0.001	Statistical significance was concluded if p ≤ 0.05.												No	Superiority or Other

Primary

LDL Cholesterol at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point

Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Apolipoprotein B at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point

Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Total Cholesterol at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point

Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Secondary

Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point

Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Triglycerides at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point

Lipoprotein (a) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point

Very low density lipoprotein (VLDL) cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Very Low Density Lipoprotein at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point

The ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol was measured at Baseline and the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

ratio

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point

Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Percent Change From Baseline in High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point

High-density lipoprotein cholesterol (HDL-C) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

percentage of baseline

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Pre-specified

High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point

The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

Full Analysis Set

Posted

Median

Inter-Quartile Range

mg/dL

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

ID	Title	Description
OG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
OG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Palpitations	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Cataract	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Conjunctivitis	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dry eye	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Eye irritation	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Eyelid cyst	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Presbyopia	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0012 affected83 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0016 affected83 at risk
Bezoar	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0014 affected83 at risk
Dental caries	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0010 affected83 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0005 affected41 at risk EG0019 affected83 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Gastritis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Lip pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0006 affected41 at risk EG00114 affected83 at risk
Oesophageal dilatation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Retching	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Tooth disorder	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Toothache	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0015 affected83 at risk
Adverse drug reaction	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Asthenia	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0011 affected83 at risk
Chills	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0016 affected83 at risk
Cyst	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Discomfort	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Facial pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG00122 affected83 at risk
Feeling jittery	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Influenza like illness	General disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG00115 affected83 at risk
Injection site discolouration	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG00113 affected83 at risk
Injection site discomfort	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00110 affected83 at risk
Injection site eczema	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Injection site erythema	General disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG00156 affected83 at risk
Injection site haematoma	General disorders	MedDRA 13.0	Systematic Assessment	EG0009 affected41 at risk EG00145 affected83 at risk
Injection site haemorrhage	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0019 affected83 at risk
Injection site induration	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00111 affected83 at risk
Injection site inflammation	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Injection site lymphadenopathy	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Injection site macule	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Injection site nodule	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0018 affected83 at risk
Injection site oedema	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0016 affected83 at risk
Injection site pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0008 affected41 at risk EG00154 affected83 at risk
Injection site papule	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0015 affected83 at risk
Injection site paraesthesia	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Injection site pruritus	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG00123 affected83 at risk
Injection site rash	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00111 affected83 at risk
Injection site reaction	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0015 affected83 at risk
Injection site recall reaction	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00115 affected83 at risk
Injection site swelling	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00113 affected83 at risk
Injection site urticaria	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Injection site vesicles	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Injection site warmth	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00112 affected83 at risk
Injury associated with device	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Irritability	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Local swelling	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Localised oedema	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Malaise	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Non-cardiac chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Oedema peripheral	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0017 affected83 at risk
Pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0015 affected83 at risk
Pyrexia	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG00110 affected83 at risk
Tenderness	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Vessel puncture site haematoma	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Hepatic cyst	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Hepatic lesion	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0015 affected83 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Abscess oral	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Asymptomatic bacteriuria	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Ear infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Eye infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Eye infection viral	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Furuncle	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
H1N1 influenza	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Influenza	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0015 affected83 at risk
Kidney infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Laryngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Localised infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Lyme disease	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0019 affected83 at risk
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Rhinitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Sinusitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0011 affected83 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0014 affected83 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0016 affected83 at risk
Vaginal infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0015 affected83 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Injury	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Muscle injury	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Sunburn	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Alanine aminotransferase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0016 affected83 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0013 affected83 at risk
Bacterial test positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0010 affected83 at risk
Blood pressure increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Body temperature increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Carotid bruit	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Computerised tomogram abdomen abnormal	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Epstein-Barr virus antibody positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Haematocrit decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Haemoglobin decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Hepatic enzyme increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0014 affected83 at risk
Herpes simplex serology positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
International normalised ratio increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Liver function test abnormal	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0015 affected83 at risk
Multiple gated acquisition scan abnormal	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Nitrite urine present	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Nuclear magnetic resonance imaging abnormal	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Platelet count decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Protein urine present	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Pulse abnormal	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Red blood cells urine positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Transaminases increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Urine leukocyte esterase positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Weight decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Weight increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
White blood cells urine positive	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0012 affected83 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Vitamin B12 deficiency	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0016 affected83 at risk
Axillary mass	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0017 affected83 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Joint warmth	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Muscle fatigue	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0013 affected83 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0018 affected83 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected41 at risk EG0014 affected83 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Sensation of heaviness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Spondylitis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Morton's neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Amnesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Burning sensation	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Disturbance in attention	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0014 affected83 at risk
Dizziness postural	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0007 affected41 at risk EG00115 affected83 at risk
Hyperaesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Lethargy	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Migraine with aura	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0014 affected83 at risk
Sciatica	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Sinus headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Anxiety	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0013 affected83 at risk
Claustrophobia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0012 affected83 at risk
Libido decreased	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Panic attack	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Stress	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Albuminuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Chromaturia	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dysuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Haematuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Proteinuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Urge incontinence	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Menstruation delayed	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0019 affected83 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0012 affected83 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0017 affected83 at risk
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Postnasal drip	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0012 affected83 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0013 affected83 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Hypoaesthesia facial	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected41 at risk EG0012 affected83 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0012 affected83 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected41 at risk EG0012 affected83 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Scab	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Skin induration	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Skin plaque	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Aortic aneurysm	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Flushing	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0011 affected83 at risk
Hot flush	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0013 affected83 at risk
Hypertension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0012 affected83 at risk
Hypotension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Infarction	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk

ID	Term
D003324	Coronary Artery Disease
D006938	Hyperlipoproteinemia Type II

ID	Term
D003327	Coronary Disease
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D014652	Vascular Diseases
D008052	Lipid Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D006951	Hyperlipoproteinemias
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Title	Description
BG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.
BG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received a placebo subcutaneous injection once a week for 26 weeks.			2	41	38	41
EG001	Mipomersen	Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.			6	83	83	83

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Coronary artery disease	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected41 at risk EG0010 affected83 at risk
Chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Non-cardiac chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected41 at risk EG0011 affected83 at risk