Safety and Efficacy of ALD518 for Reducing Oral Mucositis... | NCT01403064

Label	Type	Intervention Names
Open Label ALD518	Experimental	Biological: ALD518
ALD518 Dose 1	Experimental	Biological: ALD518
ALD518 Dose 2	Experimental	Biological: ALD518
Placebo	Placebo Comparator	Drug: 0.9% saline

Name	Type	Description	Arm Group Labels	Other Names
ALD518	Biological	IV	ALD518 Dose 1 ALD518 Dose 2 Open Label ALD518

Measure	Description	Time Frame
Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities		Up to 15 months
Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities		Up to 15 months
Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy	Gray (Gy) is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation in applications such as radiotherapy. The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy	Up to 12 weeks
Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy	The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy	Up to 12 weeks

Measure	Description	Time Frame
Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)	The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy

Name	Affiliation	Role
Jeffrey Smith, MD FRCP	Alder Biopharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Morton Plant Mease Health Care		Clearwater	Florida	33756	United States
Dana Farber Cancer Institute

ID	Title	Description
FG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
FG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment

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 of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities

Safety Population (SP) defined as any subject who received at least 1 dose of ALD518 or placebo. Subjects were analyzed based on the treatments they received. As pre-specified, the two treatment groups that received 160 mg (open label and randomized) were combined into one 160 mg group for analysis purposes of this endpoint.

Posted

Number

percentage of participants

Up to 15 months

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment or ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG002	ALD518 (320 mg)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants	OG00023 OG00132 OG00221

Title

Denominators

Categories

Adverse events (AEs)

Title	Measurements
	OG00095.7 OG001100 OG002100

Serious adverse events

Primary

Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities

SP. As pre-specified, the two treatment groups that received 160 mg (open label and randomized) were combined into one 160 mg group for analysis purposes of this endpoint.

Posted

Number

participants

Up to 15 months

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment or ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG002	ALD518 (320 mg)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants

Primary

Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy

Gray (Gy) is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation in applications such as radiotherapy. The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy

Full Analysis Population (FAP) defined as those randomized subjects who received at least 1 dose of ALD518 or placebo. Subjects were analyzed based on the treatments to which they were assigned.

Posted

Number

percentage of participants

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Primary

Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy

The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy

FAP

Posted

Number

participants

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)

The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy

FAP, 3 participants missing data

Posted

Number

percentage of participants

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)

FAP, 3 participants missing data

Posted

Number

participants

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)

The severe OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first severe OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy

FAP, 3 participants missing data

Posted

Number

percentage of participants

Measured from onset of OM through Week 12

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)

FAP, 3 participants missing data

Posted

Number

participants

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Duration of Ulcerative and Severe OM

FAP

Posted

Mean

Standard Deviation

Days

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants

Secondary

Time to Onset of Ulcerative and Severe OM

FAP

Posted

Mean

Standard Deviation

Days

Up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants

Secondary

ALD518 Plasma Concentration at Varying Weeks

Posted

Mean

Standard Deviation

ug/mL

Baseline and up to 12 weeks

ID	Title	Description
OG000	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG001	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG002	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants	OG000

Secondary

Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy)

Scored on a scale from 0 (worst possible overall health) to 10 (perfect overall health). Higher scores represent better overall health.

FAP

Posted

Mean

Standard Deviation

score on a scale

Baseline and up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) Questionnaire Overall Assessment Score at Varying Cumulative Radiation Doses (Gy)

The FACT-HN consists of 28 general + 11 head and neck specific items, each rated on a 0 (not at all) to 4 (very much) Likert type scale. The total score ranges from 0 to 148. Higher scores represent better quality of life.

FAP

Posted

Mean

Standard Deviation

score on a scale

Baseline and up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy)

The responses to the 13 items on the FACIT-F questionnaire are each measured on a 5-point Likert scale from 0 (not at all fatigued) to 4 (very much fatigued). The total score ranges from 0 to 52. Higher scores represent less fatigue.

FAP

Posted

Mean

Standard Deviation

score on a scale

Baseline and up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
OG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Secondary

Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks

The level of C-reactive protein (CRP), which can be measured in your blood, increases when there's inflammation in your body.

SP. As pre-specified, the two treatment groups that received 160 mg were combined into one 160 mg group for analysis of this endpoint.

Posted

Mean

Full Range

mg/L

Baseline and up to 12 weeks

ID	Title	Description
OG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
OG001	ALD518 (160 mg)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment and ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
OG002	ALD518 (320 mg)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Tinnitis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0013 affected32 at risk EG0020 affected21 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tongue haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0013 affected32 at risk EG0020 affected21 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Abscess limb	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Bacteraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Pseudomonas infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Blood phosphorous decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Electrocardiogram ST segment depression	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Troponin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Renal impairment	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Obstructive airway disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Pharyngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tracheal fistula	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG00110 affected32 at risk EG0024 affected21 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Erythropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0007 affected23 at risk EG00113 affected32 at risk EG0026 affected21 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Lymphatic obstruction	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0013 affected32 at risk EG0022 affected21 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected23 at risk EG00110 affected32 at risk EG0025 affected21 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0019 affected32 at risk EG0027 affected21 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Bundle branch block left	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Deafness	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Ear pain	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0015 affected32 at risk EG0023 affected21 at risk
Hyperacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Tinnitis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG0012 affected32 at risk EG0022 affected21 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hyperthyroidism	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Periorbital oedema	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0013 affected32 at risk EG0020 affected21 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Aphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Breath odor	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0022 affected21 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00013 affected23 at risk EG00122 affected32 at risk EG0029 affected21 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected23 at risk EG0017 affected32 at risk EG0023 affected21 at risk
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected23 at risk EG00111 affected32 at risk EG0025 affected21 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected23 at risk EG0014 affected32 at risk EG0021 affected21 at risk
Dysphagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected23 at risk EG00112 affected32 at risk EG0022 affected21 at risk
Epigastric discomfort	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0015 affected32 at risk EG0022 affected21 at risk
Glossitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Glossodynia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0023 affected21 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0022 affected21 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00014 affected23 at risk EG00120 affected32 at risk EG00214 affected21 at risk
Odynophagia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected23 at risk EG0015 affected32 at risk EG0024 affected21 at risk
Oral mucosal erythema	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Oral pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected23 at risk EG0013 affected32 at risk EG0027 affected21 at risk
Regurgitation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Saliva altered	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0022 affected21 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0022 affected21 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Swollen tongue	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Tongue oedema	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Tongue ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0022 affected21 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0009 affected23 at risk EG00112 affected32 at risk EG00210 affected21 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0003 affected23 at risk EG0014 affected32 at risk EG0024 affected21 at risk
Catheter site haemorrhage	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Catheter site inflammation	General disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Catheter site oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Catheter site pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0022 affected21 at risk
Drug intolerance	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Face oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0008 affected23 at risk EG0017 affected32 at risk EG0025 affected21 at risk
Hyperthermia	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Infusion site erythema	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Local swelling	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Localized oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Malaise	General disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Hyperbilirubinemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Febrile infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Hand-foot-and-mouth disease	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Herpes simplex	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Infective glossitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Laryngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Lower respiratory tract infection fungal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG0011 affected32 at risk EG0023 affected21 at risk
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected23 at risk EG00118 affected32 at risk EG0028 affected21 at risk
Oropharyngeal candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Post procedural cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Postoperative wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Pseudomonas infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Staphylococcal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Staphylococcal pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tinea cruris	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tracheostomy infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Post procedural oedema	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Radiation fibrosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0007 affected23 at risk EG0018 affected32 at risk EG0025 affected21 at risk
Suture related complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0014 affected32 at risk EG0021 affected21 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0023 affected21 at risk
Blood alkaline phosphotase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Blood bicarbonate decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Blood bilirubin increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Blood calcium decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Blood chloride decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Blood cholesterol increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0013 affected32 at risk EG0021 affected21 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0015 affected32 at risk EG0021 affected21 at risk
Blood glucose increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Blood potassium decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Blood pressure diastolic increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Blood pressure increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Blood triglycerides increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Blood urea increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
C-reactive protein increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Creatinine renal clearance decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Electrocardiogram change	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0022 affected21 at risk
Globulins decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Haematocrit decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0011 affected32 at risk EG0022 affected21 at risk
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0013 affected32 at risk EG0022 affected21 at risk
Lymphocyte count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0022 affected21 at risk
Mean cell haemoglobin concentration decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Mean cell haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Mean cell volume decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Neutrophil count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0026 affected21 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0017 affected32 at risk EG0028 affected21 at risk
Prealbumin decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Red blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Renal function test abnormal	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Reticulocyte count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0007 affected23 at risk EG00111 affected32 at risk EG00211 affected21 at risk
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0013 affected32 at risk EG0029 affected21 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0005 affected23 at risk EG0014 affected32 at risk EG0021 affected21 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0015 affected32 at risk EG0021 affected21 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0024 affected21 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0015 affected32 at risk EG0024 affected21 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Tumour ulceration	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Ageusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0013 affected32 at risk EG0022 affected21 at risk
Aphasia	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Aphonia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Cognitive disorder	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0017 affected32 at risk EG0021 affected21 at risk
Drooling	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG00012 affected23 at risk EG00111 affected32 at risk EG0025 affected21 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected23 at risk EG0016 affected32 at risk EG0023 affected21 at risk
Hypogeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Lethargy	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Myoclonus	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Polyneuropathy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Tongue biting	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Tongue paralysis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0014 affected32 at risk EG0024 affected21 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0022 affected21 at risk
Depressed mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Drug dependence	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG0016 affected32 at risk EG0021 affected21 at risk
Chromaturia	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Nocturia	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Oliguria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Polyuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Urinary retention	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0013 affected32 at risk EG0027 affected21 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected23 at risk EG0013 affected32 at risk EG0023 affected21 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Epiglottic oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0014 affected32 at risk EG0021 affected21 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0022 affected21 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Increased upper airway secretion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG0014 affected32 at risk EG0021 affected21 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0004 affected23 at risk EG0018 affected32 at risk EG0026 affected21 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Sputum discolored	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Photodermatosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Pruritis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0021 affected21 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0012 affected32 at risk EG0021 affected21 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Skin discoloration	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Aortic dilatation	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0012 affected32 at risk EG0020 affected21 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0002 affected23 at risk EG0012 affected32 at risk EG0022 affected21 at risk
Lymphoedema	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Orthostatic hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0011 affected32 at risk EG0020 affected21 at risk
Thrombophlebitis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected23 at risk EG0010 affected32 at risk EG0020 affected21 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected23 at risk EG0010 affected32 at risk EG0021 affected21 at risk

ID	Term
D009059	Mouth Diseases
D009057	Stomatognathic Diseases
D009371	Neoplasms by Site
D009369	Neoplasms

ID	Term
C000604955	clazakizumab
D000077330	Saline Solution

ID	Term
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations

ID	Title	Description
BG000	Placebo	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart
BG001	ALD518 (160 mg, OL)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment
BG002	ALD518 (160 mg, R)	ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
BG003	ALD518 (320 mg, R)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment
BG004	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	0.9% saline administered as two intravenous infusions (IV) 3 weeks apart	0	23	7	23	22	23
EG001	ALD518 (160 mg)	ALD518 160 mg IV every 4 weeks for a total of 2 doses in open-label (OL) treatment or ALD518 160 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment	4	32	15	32	32	32
EG002	ALD518 (320 mg)	ALD518 320 mg IV every 3 weeks for a total of 2 doses in randomized (R) treatment	2	21	8	21	21	21