A Randomized Phase IIa Efficacy and Safety Study of Radiu... | NCT02034552

Label	Type	Intervention Names
Radium-223 dichloride (Xofigo, BAY88-8223)	Experimental	Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Radium-223 with abiraterone&prednisone	Experimental	Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Abiraterone acetate Drug: Prednisone
Radium-223 with enzalutamide	Experimental	Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Enzalutamide

Name	Type	Description	Arm Group Labels	Other Names
Radium-223 dichloride (Xofigo, BAY88-8223)	Drug	Radium-223 dichloride (Xofigo, BAY88-8223) 50 kBq/kg (55 kBq/kg after implementation of NIST [National Institute of Standards and Technology] update) every 4 weeks x 6 doses intravenous slow bolus

Measure	Description	Time Frame
Patient Bone Scan Response Rate	Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software. Responder (R): 30% or greater resolution of the BSLA compared to baseline. Stable Disease (SD): Not meeting the criteria for R, PD, or UE. Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease. Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies.	At 24 weeks
Bone Scan Lesion Area	Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion.	At 24 weeks

Measure	Description	Time Frame
Radiological Progression Free Survival		From randomization to radiological disease progression or death from any cause (about 30.82 months )
Time to Radiological Progression		From the randomization date to the date of radiological disease progression (about 30.82months)

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Scottsdale	Arizona	85251	United States

PubMed Identifier	Type	Citation	Retractions
33744812	Derived	Petrylak DP, Vaishampayan UN, Patel KR, Higano CS, Albany C, Dawson NA, Mehlhaff BA, Quinn DI, Nordquist LT, Wagner VJ, Siegel J, Trandafir L, Sartor O. A randomized phase IIa study of quantified bone scan response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride alone or in combination with abiraterone acetate/prednisone or enzalutamide. ESMO Open. 2021 Apr;6(2):100082. doi: 10.1016/j.esmoop.2021.100082. Epub 2021 Mar 19.

ID	Title	Description
FG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
FG001	Radium-223 With Abiraterone & Prednision

ID	Title	Description
BG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
BG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
BG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00022 BG00124 BG00222 BG00368

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

Patient Bone Scan Response Rate

Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software. Responder (R): 30% or greater resolution of the BSLA compared to baseline. Stable Disease (SD): Not meeting the criteria for R, PD, or UE. Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease. Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies.

Imaging endpt analysis set (IMG): consists of mITT subj. (ITT subj. who received at least one dose of each study drug as randomized) with evaluable imaging scan at baseline, eg. bl quantitated technetium-99 bone scan imaging of sufficient completeness and quality to be assessable and having a non-zero BSLA, as determ. by the central reviewer.

Posted

Number

Percentage

At 24 weeks

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Units	Counts
Participants	OG00018 OG00119 OG00216

Title

Denominators

Categories

Responder (R)

Title	Measurements
	OG00022.2(10.1 to 39.6) OG00157.9(40.8 to 73.7) OG00250.0(31.8 to 68.2)

Stable Disease (SD)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	H0: Patient bone scan response rate at Week 24 ≤5%. The Type I error rate for the test in each treatment group, is one-sided 0.10. A one-sided p-value will be reported for this test.	Clopper and Pearson	Patient bone scan response rate at Week 24 will be estimated with exact binomial 80% CI using the method of Clopper and Pearson.	0.0109	[80% CI]: [10.1%- 39.6%]													Superiority

Primary

Bone Scan Lesion Area

Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion.

Posted

Mean

Standard Deviation

cm^2

At 24 weeks

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide

Secondary

Radiological Progression Free Survival

MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized.

Posted

Median

80% Confidence Interval

Months

From randomization to radiological disease progression or death from any cause (about 30.82 months )

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Secondary

Time to Radiological Progression

Posted

Median

80% Confidence Interval

Months

From the randomization date to the date of radiological disease progression (about 30.82months)

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Secondary

Time to Radiological Bone Progression

Posted

Median

80% Confidence Interval

Months

From the randomization date to the date of radiological bone progression (about 30.82 months)

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Secondary

Time to First Symptomatic Skeletal Event

MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized.

Posted

Median

80% Confidence Interval

Months

From the randomization date to the first SSE on or following the randomization date (about 30.82 months)

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Secondary

Symptomatic Skeletal Event-free Survival

MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized.

Posted

Median

80% Confidence Interval

Months

From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Secondary

Overall Survival

MITT analysis set: Included all ITT subjects who received at least one dose of each study drug as randomized.

Posted

Median

80% Confidence Interval

Months

From the randomization date to the date of death due to any cause (about 42.94 months)

ID	Title	Description
OG000	Radium-223 Dichloride (Xofigo, BAY88-8223)	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update) every 4 weeks x 6 doses IV (slow bolus).
OG001	Radium-223 With Abiraterone & Prednision	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus), abiraterone acetate 1000 mg daily, and prednisone 5 mg bid (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.
OG002	Radium-223 With Enzalutamide	Participants received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks x 6 doses (IV slow bolus) and enzalutamide 160 mg daily (oral). The first dose of oral co-medications is to be given after the first radium-223 dichloride injection.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0007 events3 affected19 at risk EG0015 events3 affected22 at risk EG0025 events3 affected22 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0020 events0 affected22 at risk
Angina pectoris	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cardiac disorder	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypothyroidism	Endocrine disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Cataract	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Conjunctivitis allergic	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Diplopia	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Eyelid ptosis	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Vision blurred	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Visual impairment	Eye disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Constipation	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0017 events5 affected22 at risk EG0022 events2 affected22 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0007 events4 affected19 at risk EG00115 events8 affected22 at risk EG00212 events8 affected22 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events4 affected22 at risk EG0020 events0 affected22 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0004 events2 affected19 at risk EG00111 events9 affected22 at risk EG0025 events5 affected22 at risk
Toothache	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0015 events5 affected22 at risk EG0021 events1 affected22 at risk
Anorectal discomfort	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Asthenia	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0023 events3 affected22 at risk
Chest discomfort	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Chest pain	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Chills	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Cyst	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0023 events1 affected22 at risk
Face oedema	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Fatigue	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0009 events6 affected19 at risk EG0017 events5 affected22 at risk EG00210 events8 affected22 at risk
Gait disturbance	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Influenza like illness	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Injection site pain	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Oedema	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Oedema peripheral	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0021 events1 affected22 at risk
Pyrexia	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Peripheral swelling	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Early satiety	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Bronchitis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Fungal skin infection	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0020 events0 affected22 at risk
Influenza	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events3 affected22 at risk EG0022 events2 affected22 at risk
Onychomycosis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Pyelonephritis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Tinea pedis	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Tooth abscess	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0013 events3 affected22 at risk EG0021 events1 affected22 at risk
Urinary tract infection	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0020 events0 affected22 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0024 events4 affected22 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events1 affected22 at risk
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Bone contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Eye contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0015 events2 affected22 at risk EG0024 events2 affected22 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected22 at risk EG0022 events2 affected22 at risk
Blood bilirubin increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events1 affected22 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Blood potassium decreased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Heart rate increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Lymphocyte count decreased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0024 events1 affected22 at risk
Neutrophil count decreased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Platelet count decreased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0022 events1 affected22 at risk
Weight decreased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0011 events1 affected22 at risk EG0023 events3 affected22 at risk
Weight increased	Investigations	MedDRA (19.1)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Gout	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events1 affected19 at risk EG0014 events4 affected22 at risk EG0020 events0 affected22 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Vitamin B12 deficiency	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0016 events3 affected22 at risk EG0025 events5 affected22 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0013 events2 affected22 at risk EG0024 events4 affected22 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0007 events5 affected19 at risk EG0019 events5 affected22 at risk EG00212 events9 affected22 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0020 events0 affected22 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events2 affected22 at risk EG0022 events2 affected22 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0023 events3 affected22 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0023 events3 affected22 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Akathisia	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Amnesia	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Disturbance in attention	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dizziness	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events3 affected22 at risk EG0028 events6 affected22 at risk
Dysarthria	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dysgeusia	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0026 events4 affected22 at risk
Headache	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0014 events4 affected22 at risk EG0021 events1 affected22 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Lethargy	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Spinal cord compression	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Syncope	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Poor quality sleep	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Anxiety	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Apathy	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Confusional state	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Depression	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Insomnia	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0022 events2 affected22 at risk
Middle insomnia	Psychiatric disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Calculus bladder	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Calculus urinary	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events1 affected22 at risk
Haematuria	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0022 events1 affected22 at risk
Obstructive uropathy	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Urge incontinence	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0012 events2 affected22 at risk EG0023 events2 affected22 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Oropharyngeal discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0023 events3 affected22 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events1 affected22 at risk EG0022 events2 affected22 at risk
Skin atrophy	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hypertension	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0013 events1 affected22 at risk EG0027 events4 affected22 at risk
Hypotension	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Systolic hypertension	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hot flush	Vascular disorders	MedDRA (19.1)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events3 affected22 at risk EG0025 events5 affected22 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0007 events3 affected19 at risk EG0016 events4 affected22 at risk EG0026 events4 affected22 at risk
Angina pectoris	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypothyroidism	Endocrine disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Vision blurred	Eye disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected22 at risk EG0020 events0 affected22 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Constipation	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0018 events6 affected22 at risk EG0024 events3 affected22 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0007 events4 affected19 at risk EG00116 events8 affected22 at risk EG00214 events9 affected22 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events4 affected22 at risk EG0020 events0 affected22 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0004 events2 affected19 at risk EG00112 events9 affected22 at risk EG0026 events6 affected22 at risk
Vomiting	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0016 events6 affected22 at risk EG0021 events1 affected22 at risk
Anorectal discomfort	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Asthenia	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0023 events3 affected22 at risk
Chest pain	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Chills	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Fatigue	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0009 events6 affected19 at risk EG00111 events8 affected22 at risk EG00211 events9 affected22 at risk
Influenza like illness	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Oedema peripheral	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0015 events4 affected22 at risk EG0022 events2 affected22 at risk
Pyrexia	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Peripheral swelling	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0022 events2 affected22 at risk
Bronchitis	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Influenza	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Nasopharyngitis	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0014 events4 affected22 at risk EG0022 events2 affected22 at risk
Tooth abscess	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0015 events5 affected22 at risk EG0022 events2 affected22 at risk
Urinary tract infection	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0020 events0 affected22 at risk
Accident	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0015 events3 affected22 at risk EG0023 events2 affected22 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0024 events4 affected22 at risk
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0023 events2 affected22 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Alanine aminotransferase increased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0015 events2 affected22 at risk EG0024 events2 affected22 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected22 at risk EG0023 events2 affected22 at risk
Blood potassium decreased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Platelet count decreased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0023 events1 affected22 at risk
Weight decreased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0011 events1 affected22 at risk EG0023 events3 affected22 at risk
Weight increased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Gout	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events1 affected19 at risk EG0014 events4 affected22 at risk EG0021 events1 affected22 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0016 events3 affected22 at risk EG0025 events5 affected22 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0018 events5 affected22 at risk EG0029 events6 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0007 events5 affected19 at risk EG00113 events8 affected22 at risk EG00217 events9 affected22 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0014 events3 affected22 at risk EG0020 events0 affected22 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0014 events3 affected22 at risk EG0024 events4 affected22 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0023 events3 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0017 events3 affected22 at risk EG0026 events4 affected22 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0023 events2 affected22 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Dizziness	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events3 affected22 at risk EG0028 events6 affected22 at risk
Dysgeusia	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0026 events4 affected22 at risk
Headache	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0015 events5 affected22 at risk EG0021 events1 affected22 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0023 events2 affected22 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected22 at risk EG0023 events2 affected22 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Syncope	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Confusional state	Psychiatric disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Insomnia	Psychiatric disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected22 at risk EG0022 events2 affected22 at risk
Haematuria	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0020 events0 affected22 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0022 events1 affected22 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0022 events2 affected22 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected19 at risk EG0013 events3 affected22 at risk EG0025 events3 affected22 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0024 events4 affected22 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0012 events1 affected22 at risk EG0022 events2 affected22 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Hypertension	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected19 at risk EG0016 events2 affected22 at risk EG00213 events6 affected22 at risk
Hypotension	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Hot flush	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected19 at risk EG0013 events3 affected22 at risk EG0025 events5 affected22 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
C581106	radium Ra 223 dichloride
D000069501	Abiraterone Acetate
D011241	Prednisone
C540278	enzalutamide

ID	Term
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Radium-223	Radium-223	0	19	2	19	18	19
EG001	Radium-223 + Abiraterone Acetate + Prednisone	Radium-223 + Abiraterone Acetate + Prednisone	0	22	10	22	22	22
EG002	Radium-223 + Enzalutamide	Radium-223 + Enzalutamide	1	22	8	22	22	22

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0020 events0 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
General physical health deterioration	General disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0003 events2 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Non-systematic Assessment	EG0008 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Dizziness	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Syncope	Nervous system disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0023 events3 affected22 at risk
Haematuria	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events1 affected22 at risk EG0020 events0 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Chest pain	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
General physical health deterioration	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Pneumonia	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Tooth abscess	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events2 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0008 events1 affected19 at risk EG0010 events0 affected22 at risk EG0020 events0 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0021 events1 affected22 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected22 at risk EG0021 events1 affected22 at risk
Dizziness	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Syncope	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0023 events3 affected22 at risk
Haematuria	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected22 at risk EG0020 events0 affected22 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected22 at risk EG0021 events1 affected22 at risk