Ascending Multiple Dose Study to Evaluate the Safety, Tol... | NCT01133522

Label	Type	Description	Intervention Names
Evolocumab	Experimental	Participants received one of 5 dose levels of evolocumab administered as multiple subcutaneous doses.	Biological: Evolocumab
Placebo	Placebo Comparator	Participants received matching placebo dose regimens by subcutaneous injection.	Biological: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Evolocumab	Biological	Administered by subcutaneous injection	Evolocumab

Measure	Description	Time Frame
Number of Participants With Adverse Events	The relationship of each adverse event to the investigational product was assessed by the investigator. A serious adverse event (SAE) is defined as an adverse event that is fatal is life threatening (places the subject at immediate risk of death) requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity is a congenital anomaly/birth defect other significant medical hazard.	From the first dose of study drug until Day 85
Number of Participants With Anti-Evolocumab Antibodies	Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies	From the first dose of study drug until Day 85

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Evolocumab	Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 800 ng/mL.	Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Men and women ages 18 to 70 years (inclusive) at the time of screening with hyperlipidemia
Body mass index (BMI) ≥18 and ≤ 35 kg/m^2 at the time of screening
Low-density lipoprotein cholesterol (LDL-C) level of 70-220 mg/dL (inclusive) at screening as measured by direct assay
For Cohorts 1-5: On a stable dose of rosuvastatin (Crestor) < 40 mg/day, atorvastatin (Lipitor) < 80 mg/day, or simvastatin (Zocor) 20-80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
For Cohort 6: On a stable dose of rosuvastatin (Crestor) 40 mg/day or atorvastatin (Lipitor) 80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
For Cohort 7: Diagnosis of heterozygous familial hypercholesterolemia, based on a score of ≥ 9 points using the World health Organization (WHO) criteria

Exclusion Criteria:

Diagnosis of homozygous familial hypercholesterolemia
History of heart failure, coronary artery bypass graft, or cardiac arrhythmia
History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina) or percutaneous coronary intervention, within 12 months prior to enrollment
Planned cardiac surgery or revascularization
Known aortic, peripheral vascular or cerebrovascular disease (including history of stroke or transient ischemic attack)
Diabetes mellitus with any of the following:
1. known microvascular or macrovascular disease
2. HbA1c > 8.0% at screening
3. use of any hypoglycemic medication other than metformin
Uncontrolled hypertension (systolic blood pressure ≥ 150 or diastolic blood pressure ≥ 90 mmHg) either on or off therapy at screening or at baseline

Name	Affiliation	Role
MD	Amgen	Study Director

PubMed Identifier	Type	Citation	Retractions
23083772	Background	Dias CS, Shaywitz AJ, Wasserman SM, Smith BP, Gao B, Stolman DS, Crispino CP, Smirnakis KV, Emery MG, Colbert A, Gibbs JP, Retter MW, Cooke BP, Uy ST, Matson M, Stein EA. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012 Nov 6;60(19):1888-98. doi: 10.1016/j.jacc.2012.08.986. Epub 2012 Oct 17.

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
FG001	Evolocumab 14 mg QW × 6

Arm/Group Information

ID	Title	Description
BG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
BG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
BG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
BG003	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
BG004	Evolocumab 280 mg Q2W × 3	Cohort 4: Participants on low-to-moderate-dose statin therapy received evolocumab 280 mg subcutaneous injection every 2 weeks for 6 weeks.
BG005	Evolocumab 420 mg Q4W × 2	Cohort 5: participants on low-to-moderate-dose statin therapy received evolocumab 420 mg subcutaneous injection every 4 weeks for 8 weeks.
BG006	High Dose Statin - Placebo	Cohort 6: Participants on high-dose statin therapy received placebo subcutaneous injection every 2 weeks for 6 weeks.
BG007	High Dose Statin - Evolocumab 140 mg Q2W × 3	Cohort 6: Participants on high-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
BG008	HeFH - Placebo	Cohort 7: Participants diagnosed with HeFH received placebo subcutaneous injection every 2 weeks for 6 weeks.
BG009	HeFH - Evolocumab 140 mg Q2W × 3	Cohort 7: Participants diagnosed with HeFH received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
BG010	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG0016 BG0026 BG0036 BG0046 BG0056 BG0062 BG0079 BG0082 BG0094 BG01057

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

Number of Participants With Adverse Events

The relationship of each adverse event to the investigational product was assessed by the investigator.

A serious adverse event (SAE) is defined as an adverse event that

is fatal
is life threatening (places the subject at immediate risk of death)
requires in-patient hospitalization or prolongation of existing hospitalization
results in persistent or significant disability/incapacity
is a congenital anomaly/birth defect
other significant medical hazard.

Safety analysis set

Posted

Number

participants

From the first dose of study drug until Day 85

ID	Title	Description
OG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
OG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG003	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
OG004	Evolocumab 280 mg Q2W × 3	Cohort 4: Participants on low-to-moderate-dose statin therapy received evolocumab 280 mg subcutaneous injection every 2 weeks for 6 weeks.
OG005	Evolocumab 420 mg Q4W × 2	Cohort 5: participants on low-to-moderate-dose statin therapy received evolocumab 420 mg subcutaneous injection every 4 weeks for 8 weeks.
OG006	High Dose Statin - Placebo	Cohort 6: Participants on high-dose statin therapy received placebo subcutaneous injection every 2 weeks for 6 weeks.
OG007	High Dose Statin - Evolocumab 140 mg Q2W × 3	Cohort 6: Participants on high-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
OG008	HeFH - Placebo	Cohort 7: Participants diagnosed with HeFH received placebo subcutaneous injection every 2 weeks for 6 weeks.
OG009	HeFH - Evolocumab 140 mg Q2W × 3	Cohort 7: Participants diagnosed with HeFH received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.

Units	Counts
Participants	OG00010 OG0016 OG0026 OG003

Title

Denominators

Categories

Any adverse event

Title	Measurements
	OG0007 OG0012 OG0025 OG003

Secondary

Maximum Observed Plasma Concentration (Cmax) of Evolocumab

Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 800 ng/mL.

The Pharmacokinetic analysis set consisted of all participants for whom at least 1 pharmacokinetic parameter or endpoint could be adequately estimated. Serum evolocumab concentrations were not detectable in Cohorts 1 and 2.

Posted

Mean

Standard Deviation

μg/mL

Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85

ID	Title	Description
OG000	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG001	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.

Primary

Number of Participants With Anti-Evolocumab Antibodies

Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies

Safety analysis set

Posted

Number

participants

From the first dose of study drug until Day 85

ID	Title	Description
OG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
OG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG003	Evolocumab 140 mg Q2W × 3

Secondary

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab

Area under the unbound evolocumab serum concentration-time curve from time of last dose to time of last quantifiable concentration following the last dose of evolocumab.

Pharmacokinetic analysis set with available data

Posted

Mean

Standard Deviation

day*μg/mL

Day 29 predose (last dose for Cohorts 3-7) and Days 36 (predose for Cohorts 1 and 2), 40, 43, 50, 57, 64, 71, 78, and 85

ID	Title	Description
OG000	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG001	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.
OG003

Secondary

Percent Change From Baseline to End of the Dosing Interval in LDL-C

Participants with non-missing data

Posted

Mean

Standard Deviation

percent change

Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group

ID	Title	Description
OG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
OG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG003	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.

Secondary

Percent Change From Baseline to End of the Dosing Interval in PCSK9

Serum PCSK9 concentrations were determined by using a qualified enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 15 ng/mL.

Participants with non-missing data

Posted

Mean

Standard Deviation

percent change

Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group

ID	Title	Description
OG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.
OG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.
OG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.
OG003	Evolocumab 140 mg Q2W × 3

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Cohorts 1-5 Combined: Participants on low-to-moderate dose statin therapy received placebo subcutaneous injections matching active investigational product in volume and frequency.	10	7	10
EG001	Evolocumab 14 mg QW × 6	Cohort 1: Participants on low-to-moderate-dose stain therapy received evolocumab 14 mg subcutaneous injection once weekly for 6 weeks.	6	2	6
EG002	Evolocumab 35 mg QW × 6	Cohort 2: Participants on low-to-moderate-dose statin therapy received evolocumab 35 mg subcutaneous injection once weekly for 6 weeks.	6	5	6
EG003	Evolocumab 140 mg Q2W × 3	Cohort 3: Participants on low-to-moderate-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.	6	4	6
EG004	Evolocumab 280 mg Q2W × 3	Cohort 4: Participants on low-to-moderate-dose statin therapy received evolocumab 280 mg subcutaneous injection every 2 weeks for 6 weeks.	6	6	6
EG005	Evolocumab 420 mg Q4W × 2	Cohort 5: participants on low-to-moderate-dose statin therapy received evolocumab 420 mg subcutaneous injection every 4 weeks for 8 weeks.	6	3	6
EG006	High Dose Statin - Placebo	Cohort 6: Participants on high-dose statin therapy received placebo subcutaneous injection every 2 weeks for 6 weeks.	2	1	2
EG007	High Dose Statin - Evolocumab 140 mg Q2W × 3	Cohort 6: Participants on high-dose statin therapy received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.	9	7	9
EG008	HeFH - Placebo	Cohort 7: Participants diagnosed with HeFH received placebo subcutaneous injection every 2 weeks for 6 weeks.	2	1	2
EG009	HeFH - Evolocumab 140 mg Q2W × 3	Cohort 7: Participants diagnosed with HeFH received evolocumab 140 mg subcutaneous injection every 2 weeks for 6 weeks.	4	1	4

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain lower	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG0030 affected6 at risk EG0040 affected6 at risk EG0050 affected6 at risk EG0061 affected2 at risk EG0070 affected9 at risk EG0080 affected2 at risk EG0090 affected4 at risk
Dental caries	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Injection site haematoma	General disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Injection site haemorrhage	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected6 at risk EG0020 affected6 at risk EG003
Injection site pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Bronchitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Sinusitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Eosinophil count increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected6 at risk EG0020 affected6 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Presyncope	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Lipoma excision	Surgical and medical procedures	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Varicose vein	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Asthenia	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Injection site reaction	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Vessel puncture site pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Localised infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Cardiac murmur	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Liver function test abnormal	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected6 at risk EG0020 affected6 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected6 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0021 affected6 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected10 at risk EG0010 affected6 at risk EG0020 affected6 at risk EG003

ID	Term
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases