A 4-year Extension Study to Core 1-year Study of Iron Che... | NCT00390858

Label	Type	Description	Intervention Names
Deferasirox	Experimental	Initial dose of 10 mg/kg, dose modifications of ± 5 or 10 mg/kg were based on participant response.	Drug: Deferasirox

Name	Type	Description	Arm Group Labels	Other Names
Deferasirox	Drug	Deferasirox in children from 1 to 18 years old was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters and on increasing or decreasing Liver Iron Concentration (LIC), and serum ferritin. Deferasirox was available as 125 mg, 250 mg and 500 mg tablets.

Measure	Description	Time Frame
Participants With Adverse Events by Primary System Organ Class (SOC)	Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.	4 year extension + core 1 year
Change in Liver Iron Concentration (LIC)	Change in Liver Iron Concentration [LIC] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw)	Baseline of Core Study to End of Extension Study, up to 5 years.

Measure	Description	Time Frame
Total Body Iron Elimination (TBIE) Rate (mg/kg/Day)	Total Iron Body Elimination (TBIE) Rate [mg/kg/Day] was calculated for each patient based on SQUID ( Superconducting Quantum Interference Device) results.	Baseline of Core Study to End of Extension Study, up to 5 years
Relative Change in Serum Ferritin Level

Name	Affiliation	Role
Dr. Gianluca Forni	Novartis Pharmaceuticals	Study Director
Prof. Renzo Galanello	Novartis Pharmaceuticals	Study Director
Prof. Antonio Piga	Novartis Pharmaceuticals	Study Director
Dr. Yves Bertrand	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Lyon			France
Novartis Investigative Site

ID	Title	Description
FG000	Children ( < 12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing

ID	Title	Description
BG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
BG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00120 BG00240

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

Participants With Adverse Events by Primary System Organ Class (SOC)

Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.

The safety set comprising of all the 40 patients who received at least one dose of deferasirox during the core or extension study was used in all analyses.

Posted

Number

participants

4 year extension + core 1 year

ID	Title	Description
OG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
OG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing

Units	Counts
Participants	OG00020 OG00120

Title

Denominators

Categories

Patients with at least one Adverse Event (AE)

Title	Measurements
	OG00020 OG00120

General disorders & administration site conditions

Title	Measurements
	OG000

Primary

Change in Liver Iron Concentration (LIC)

Change in Liver Iron Concentration [LIC] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw)

The safety set was used for all analyses. This comprised of all 40 patients who received at least one dose of deferasirox during the core or extension study.

Posted

Mean

Standard Deviation

mg Fe/g dw

Baseline of Core Study to End of Extension Study, up to 5 years.

ID	Title	Description
OG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
OG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing

Secondary

Total Body Iron Elimination (TBIE) Rate (mg/kg/Day)

Total Iron Body Elimination (TBIE) Rate [mg/kg/Day] was calculated for each patient based on SQUID ( Superconducting Quantum Interference Device) results.

The safety set was used for all analyses. This comprised of all 40 patients who received at least one dose of deferasirox during the core or extension study.

Posted

Mean

Standard Deviation

mg/kg/Day

Baseline of Core Study to End of Extension Study, up to 5 years

ID	Title	Description
OG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
OG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing

Secondary

Relative Change in Serum Ferritin Level

Serum levels were drawn at the baseline of the Core Study up to 18 months of the Extension Study. Levels were analyzed for serum ferritin measured in micrograms per Liter. Relative change (%) in serum ferritin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in ferritin level from Baseline/Baseline level) x 100.

The safety set was used for all analyses. This comprised of all 40 patients who received at least one dose of deferasirox during the core or extension study.

Posted

Mean

Standard Deviation

percent change

Baseline of Core Study to Extension 18 months, up to 2.5 years.

ID	Title	Description
OG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing
OG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters (e.g. renal and hematology) and whether Liver Iron Concentration (LIC), and serum ferritin were increasing or decreasing

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Children (<12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters ( renal and hematology) and whether Liver Iron Concentration (LIC) and serum ferritin were increasing or decreasing			4	20	20	20
EG001	Adolescents ( ≧12 Years)	Deferasirox was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters ( renal and hematology) and whether Liver Iron Concentration (LIC) and serum ferritin were increasing or decreasing			8	20	20	20

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Splenomegaly	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pancreatolithiasis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Local swelling	General disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Biliary colic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Infectious mononucleosis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Transaminases increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pelvic fluid collection	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cholecystectomy	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Splenectomy	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Tonsillectomy	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0014 affected20 at risk
Splenomegaly	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cardiomyopathy	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Extrasystoles	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0012 affected20 at risk
Talipes	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Auricular pseudocyst	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Ear pain	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0008 affected20 at risk EG0014 affected20 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Growth hormone deficiency	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Hypogonadism	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Hypothyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Conjunctivitis	Eye disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0014 affected20 at risk
Conjunctivitis allergic	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Eye irritation	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Eyelid oedema	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Hypermetropia	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Lacrimation increased	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Ocular icterus	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Retinal degeneration	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Retinopathy	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Vision blurred	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00015 affected20 at risk EG00110 affected20 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0018 affected20 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cheilitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Dental caries	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0008 affected20 at risk EG0019 affected20 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Enteritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0014 affected20 at risk
Flatulence	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Gingivitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Intestinal congestion	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG00110 affected20 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0014 affected20 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00012 affected20 at risk EG0019 affected20 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0007 affected20 at risk EG0018 affected20 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Cyst	General disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Hyperpyrexia	General disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Influenza like illness	General disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0011 affected20 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG00018 affected20 at risk EG00116 affected20 at risk
Suprapubic pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Biliary colic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0014 affected20 at risk
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Allergy to plants	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Food allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Acute tonsillitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Bacterial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected20 at risk EG0015 affected20 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Catheter related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Ear infection	Infections and infestations	MedDRA	Systematic Assessment	EG0009 affected20 at risk EG0012 affected20 at risk
Fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0012 affected20 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG00010 affected20 at risk EG0018 affected20 at risk
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Genital infection female	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Herpes simplex	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Impetigo	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0007 affected20 at risk EG00111 affected20 at risk
Laryngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Leptospirosis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Localised infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Lymphangitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected20 at risk EG0012 affected20 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0012 affected20 at risk
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00012 affected20 at risk EG00110 affected20 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0014 affected20 at risk
Pyoderma	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG00017 affected20 at risk EG00113 affected20 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Skin infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Subcutaneous abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Tinea versicolour	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Tonsillitis	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0015 affected20 at risk
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Tracheitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0012 affected20 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Varicella	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected20 at risk EG0011 affected20 at risk
Vulvitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Chest injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Eye injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Foreign body trauma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0010 affected20 at risk
Sunburn	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Vertebral injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Wound	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Beta 2 microglobulin urine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Blood bilirubin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0012 affected20 at risk
Blood folate decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Blood homocysteine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Creatinine renal clearance decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Glomerular filtration rate abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Glucose urine present	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Protein C decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Transaminases increased	Investigations	MedDRA	Systematic Assessment	EG0008 affected20 at risk EG0012 affected20 at risk
Urinary casts	Investigations	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Urine protein/creatinine ratio increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Vitamin E decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0014 affected20 at risk
White blood cell count increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Hyperinsulinism	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Hypozincaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Vitamin C deficiency	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0012 affected20 at risk
Zinc deficiency	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0015 affected20 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected20 at risk EG0013 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0019 affected20 at risk
Bone swelling	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0010 affected20 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0013 affected20 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Neck mass	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0012 affected20 at risk
Torticollis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0013 affected20 at risk
Aphonia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Disturbance in attention	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0009 affected20 at risk EG00112 affected20 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Presyncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Nervousness	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Haematuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Nephropathy toxic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pollakiuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0012 affected20 at risk
Renal colic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Amenorrhoea	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0013 affected20 at risk
Breast discomfort	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0014 affected20 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Menstrual disorder	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Polymenorrhoea	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00018 affected20 at risk EG00116 affected20 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected20 at risk EG0013 affected20 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0007 affected20 at risk EG0019 affected20 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected20 at risk EG0010 affected20 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0012 affected20 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Pityriasis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Pityriasis alba	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0011 affected20 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0010 affected20 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0010 affected20 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected20 at risk EG0012 affected20 at risk
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk

ID	Term
D019189	Iron Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds