A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Andro... | NCT02489318

ID	Type	Description	Link
56021927PCR3002	Other Identifier	Janssen Research & Development, LLC
2015-000735-32	EudraCT Number

Label	Type	Description	Intervention Names
Apalutamide plus ADT	Experimental	Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT.	Drug: Apalutamide Drug: Androgen Deprivation Therapy (ADT)
Placebo plus ADT	Experimental	Participants will receive matching Placebo with ADT.	Drug: Placebo Drug: Androgen Deprivation Therapy (ADT)

Name	Type	Description	Arm Group Labels	Other Names
Apalutamide	Drug	Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.	Apalutamide plus ADT

Measure	Description	Time Frame
Radiographic Progression-free Survival (rPFS)	rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.	Up to 35 months
Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause.	Up to 57 months

Measure	Description	Time Frame
Time to Initiation of Cytotoxic Chemotherapy	Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.	Up to 57 months
Time to Pain Progression

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of prostate adenocarcinoma as confirmed by the investigator
Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1
Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization
Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization
Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies

Exclusion Criteria:

Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
Known brain metastases
Lymph nodes as only sites of metastases
Visceral (ie, liver or lung) metastases as only sites of metastases
Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer
History of seizures or medications known to lower seizure threshold

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
39163505	Derived	Karsh LI, Bevans KB, Saad F, Chung BH, Oudard S, Brookman-May SD, McCarthy SA, Smith MR, Chi KN, Small EJ, Agarwal N. Prostate-specific antigen and health-related quality of life in individuals with advanced prostate cancer treated with apalutamide: a plain language summary of the SPARTAN and TITAN studies. Future Oncol. 2024;20(35):2689-2698. doi: 10.1080/14796694.2024.2384257. Epub 2024 Aug 20.
39058790

ID	Title	Description
FG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 16, 2020	Sep 6, 2021

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

Radiographic Progression-free Survival (rPFS)

rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1.

Intent to treat (ITT) population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 35 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
OG001	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Units	Counts
Participants	OG000527 OG001525

Title

Denominators

Categories

Title	Measurements
	OG00022.08(18.46 to 32.92) OG001NA(NA to NA)Here NA signifies that the median, lower limit and upper limit of confidence interval (CI) were not estimable due to lesser number of events.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		<0.0001		Hazard Ratio (HR)	0.484			2-Sided	95	0.391	0.600					Superiority

Primary

Overall Survival (OS)

OS was defined as the time from date of randomization to date of death from any cause.

ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 57 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
OG001	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Secondary

Time to Initiation of Cytotoxic Chemotherapy

Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.

ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 57 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
OG001	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Secondary

Time to Pain Progression

Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (>=) 3 weeks apart or initiation of chronic opioids, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3 (worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.

ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 57 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Secondary

Time to Chronic Opioid Use

Time to chronic opioid use was defined as the time from date of randomization to the first date of confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (>=) 3 weeks for oral or >=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a >=30 percent (%) increase in total daily dose of the opioid analgesics lasting for >= 3 weeks for oral or >= 7 days for non-oral formulation.

ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 57 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
OG001	Apalutamide + ADT

Secondary

Time to Skeletal-related Event (SRE)

Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone.

ITT population included all randomized participants classified according to their assigned treatment group, regardless of the actual treatment received.

Posted

Median

95% Confidence Interval

months

Up to 57 months

ID	Title	Description
OG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
OG001	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0006 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Acute Coronary Syndrome	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Angina Pectoris	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Angina Unstable	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Aortic Valve Disease Mixed	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Arteriosclerosis Coronary Artery	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Atrioventricular Block Complete	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cardiac Amyloidosis	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cardiac Disorder	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cardiac Failure	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cardiac Failure Chronic	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Cor Pulmonale Chronic	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Coronary Artery Disease	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Coronary Artery Occlusion	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Coronary Artery Stenosis	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Mitral Valve Disease	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Myocardial Infarction	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0028 affected524 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Sinoatrial Block	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Sinus Node Dysfunction	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Supraventricular Extrasystoles	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Supraventricular Tachycardia	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Ventricular Fibrillation	Cardiac disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Vertigo Positional	Ear and labyrinth disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Goitre	Endocrine disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cataract	Eye disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Open Angle Glaucoma	Eye disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Anal Fistula	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Dyschezia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Dysphagia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Gastric Ulcer Perforation	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Gastritis	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Haemorrhagic Erosive Gastritis	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Inguinal Hernia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Large Intestinal Ulcer Perforation	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Large Intestine Polyp	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0021 affected524 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Proctalgia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Terminal Ileitis	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Umbilical Hernia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Asthenia	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Exercise Tolerance Decreased	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Fatigue	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0003 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Gait Disturbance	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
General Physical Health Deterioration	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0012 affected208 at risk EG0020 affected524 at risk
Oedema	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pain	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Performance Status Decreased	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Peripheral Swelling	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Pyrexia	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Bile Duct Stone	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cholangiolitis	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Cholangitis Acute	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cholecystitis Acute	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hepatic Cirrhosis	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hepatic Failure	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Jaundice	Hepatobiliary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Abdominal Abscess	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Abscess Jaw	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Abscess Oral	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Bronchiolitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Bronchitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0011 affected208 at risk EG0023 affected524 at risk
Cellulitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cholecystitis Infective	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Covid-19	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Erysipelas	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Fournier's Gangrene	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Infected Lymphocele	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Influenza	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Kidney Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Klebsiella Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Localised Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Muscle Abscess	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Peritonitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pneumonia	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0003 affected527 at risk EG0013 affected208 at risk EG00210 affected524 at risk
Pneumonia Bacterial	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Pulmonary Tuberculosis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Pyelonephritis Acute	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Sepsis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0012 affected208 at risk EG0020 affected524 at risk
Septic Shock	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Sinusitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Staphylococcal Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Tuberculosis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Urinary Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0011 affected208 at risk EG0025 affected524 at risk
Urosepsis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0025 affected524 at risk
Viral Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Viral Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Acetabulum Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Brain Contusion	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Clavicle Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Comminuted Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Femoral Neck Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Forearm Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hand Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Incisional Hernia	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Ligament Sprain	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Lower Limb Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Patella Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Radius Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Skull Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Soft Tissue Injury	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0024 affected524 at risk
Subarachnoid Haematoma	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Subdural Haemorrhage	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Thoracic Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Tibia Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Traumatic Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
International Normalised Ratio Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Weight Decreased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Diabetes Mellitus Inadequate Control	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0012 affected208 at risk EG0020 affected524 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0024 affected524 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0006 affected527 at risk EG0010 affected208 at risk EG0024 affected524 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0012 affected208 at risk EG0020 affected524 at risk
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Lumbar Spinal Stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0004 affected527 at risk EG0011 affected208 at risk EG0021 affected524 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pathological Fracture	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0004 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Rheumatoid Arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Rotator Cuff Syndrome	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Adenocarcinoma of Colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Adrenal Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Benign Lung Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Bladder Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Burkitt's Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cancer Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Gastric Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Leiomyosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Lung Carcinoma Cell Type Unspecified Stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Lung Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Metastases to Central Nervous System	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Non-Small Cell Lung Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Respiratory Papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Cauda Equina Syndrome	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Cerebral Haemorrhage	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0013 affected208 at risk EG0024 affected524 at risk
Cognitive Disorder	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Diplegia	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Dizziness	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Haemorrhage Intracranial	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0011 affected208 at risk EG0021 affected524 at risk
Hydrocephalus	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0021 affected524 at risk
Iiird Nerve Paresis	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Migraine	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Paraplegia	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Presyncope	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Seizure	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Spinal Cord Compression	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0006 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Subarachnoid Haemorrhage	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0022 affected524 at risk
Device Malfunction	Product Issues	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Confusional State	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Mental Status Changes	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Suicidal Ideation	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Suicide Attempt	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Bladder Perforation	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Bladder Tamponade	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Calculus Bladder	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Calculus Urinary	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0003 affected527 at risk EG0011 affected208 at risk EG00210 affected524 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0004 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Renal Disorder	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Renal Failure	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Ureteric Obstruction	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Urethral Stenosis	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Urinary Bladder Haematoma	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Urinary Retention	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0009 affected527 at risk EG0010 affected208 at risk EG0024 affected524 at risk
Urinary Tract Obstruction	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Benign Prostatic Hyperplasia	Reproductive system and breast disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0011 affected208 at risk EG0022 affected524 at risk
Acute Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0022 affected524 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0003 affected527 at risk EG0011 affected208 at risk EG0023 affected524 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0012 affected208 at risk EG0020 affected524 at risk
Organising Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Paranasal Cyst	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Pleuritic Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk
Pneumothorax Spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0023 affected524 at risk
Pulmonary Haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Pulmonary Mass	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0021 affected524 at risk
Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0020 affected524 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0012 affected208 at risk EG0023 affected524 at risk
Drug Eruption	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0001 affected527 at risk EG0010 affected208 at risk EG0021 affected524 at risk
Hypertension	Vascular disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0023 affected524 at risk
Venous Stenosis	Vascular disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0011 affected208 at risk EG0020 affected524 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00071 affected527 at risk EG00113 affected208 at risk EG00268 affected524 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00021 affected527 at risk EG0018 affected208 at risk EG00229 affected524 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0012 affected208 at risk EG00216 affected524 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0016 affected208 at risk EG00212 affected524 at risk
Hypothyroidism	Endocrine disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0005 affected527 at risk EG0015 affected208 at risk EG00223 affected524 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00022 affected527 at risk EG0013 affected208 at risk EG00217 affected524 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00013 affected527 at risk EG0012 affected208 at risk EG00217 affected524 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00057 affected527 at risk EG0016 affected208 at risk EG00258 affected524 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00035 affected527 at risk EG00111 affected208 at risk EG00256 affected524 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00010 affected527 at risk EG0012 affected208 at risk EG00212 affected524 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00044 affected527 at risk EG00112 affected208 at risk EG00241 affected524 at risk
Toothache	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00011 affected527 at risk EG0011 affected208 at risk EG00210 affected524 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00023 affected527 at risk EG0013 affected208 at risk EG00222 affected524 at risk
Asthenia	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00045 affected527 at risk EG0018 affected208 at risk EG00240 affected524 at risk
Fatigue	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00087 affected527 at risk EG00115 affected208 at risk EG002107 affected524 at risk
Influenza Like Illness	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00017 affected527 at risk EG0013 affected208 at risk EG00216 affected524 at risk
Oedema Peripheral	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00041 affected527 at risk EG0014 affected208 at risk EG00232 affected524 at risk
Pyrexia	General disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00016 affected527 at risk EG0014 affected208 at risk EG00215 affected524 at risk
Bronchitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00012 affected527 at risk EG0011 affected208 at risk EG00218 affected524 at risk
Conjunctivitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG0005 affected527 at risk EG0012 affected208 at risk EG00213 affected524 at risk
Herpes Zoster	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00011 affected527 at risk EG0010 affected208 at risk EG00210 affected524 at risk
Influenza	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00023 affected527 at risk EG0015 affected208 at risk EG00221 affected524 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00047 affected527 at risk EG0016 affected208 at risk EG00244 affected524 at risk
Pneumonia	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00014 affected527 at risk EG0014 affected208 at risk EG00211 affected524 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00029 affected527 at risk EG0016 affected208 at risk EG00240 affected524 at risk
Urinary Tract Infection	Infections and infestations	MedDRA Version 23.0	Non-systematic Assessment	EG00022 affected527 at risk EG0014 affected208 at risk EG00228 affected524 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG00011 affected527 at risk EG0014 affected208 at risk EG00211 affected524 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG00036 affected527 at risk EG0018 affected208 at risk EG00247 affected524 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA Version 23.0	Non-systematic Assessment	EG00014 affected527 at risk EG0011 affected208 at risk EG00214 affected524 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00042 affected527 at risk EG0014 affected208 at risk EG00225 affected524 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00043 affected527 at risk EG0015 affected208 at risk EG00218 affected524 at risk
Blood Alkaline Phosphatase Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00032 affected527 at risk EG0013 affected208 at risk EG00218 affected524 at risk
Blood Lactate Dehydrogenase Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00017 affected527 at risk EG0010 affected208 at risk EG0029 affected524 at risk
Blood Thyroid Stimulating Hormone Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0013 affected208 at risk EG00216 affected524 at risk
Weight Decreased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00029 affected527 at risk EG0019 affected208 at risk EG00243 affected524 at risk
Weight Increased	Investigations	MedDRA Version 23.0	Non-systematic Assessment	EG00092 affected527 at risk EG0017 affected208 at risk EG00255 affected524 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00027 affected527 at risk EG00111 affected208 at risk EG00232 affected524 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0008 affected527 at risk EG0017 affected208 at risk EG00234 affected524 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00011 affected527 at risk EG0011 affected208 at risk EG00218 affected524 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00027 affected527 at risk EG00116 affected208 at risk EG00247 affected524 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00013 affected527 at risk EG0015 affected208 at risk EG00222 affected524 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00016 affected527 at risk EG0012 affected208 at risk EG0027 affected524 at risk
Vitamin D Deficiency	Metabolism and nutrition disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0000 affected527 at risk EG0010 affected208 at risk EG00212 affected524 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00082 affected527 at risk EG00115 affected208 at risk EG002101 affected524 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG000108 affected527 at risk EG00111 affected208 at risk EG002106 affected524 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00053 affected527 at risk EG0010 affected208 at risk EG00239 affected524 at risk
Groin Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0007 affected527 at risk EG0012 affected208 at risk EG00211 affected524 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00010 affected527 at risk EG0012 affected208 at risk EG00221 affected524 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00012 affected527 at risk EG0012 affected208 at risk EG00218 affected524 at risk
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0012 affected208 at risk EG00221 affected524 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00041 affected527 at risk EG0015 affected208 at risk EG00239 affected524 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00019 affected527 at risk EG0012 affected208 at risk EG00210 affected524 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0007 affected527 at risk EG0010 affected208 at risk EG00216 affected524 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00067 affected527 at risk EG0018 affected208 at risk EG00269 affected524 at risk
Pathological Fracture	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0005 affected527 at risk EG0010 affected208 at risk EG00211 affected524 at risk
Spinal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00012 affected527 at risk EG0013 affected208 at risk EG00213 affected524 at risk
Dizziness	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00035 affected527 at risk EG0017 affected208 at risk EG00224 affected524 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0012 affected208 at risk EG00213 affected524 at risk
Headache	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00031 affected527 at risk EG00112 affected208 at risk EG00244 affected524 at risk
Hypoaesthesia	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00012 affected527 at risk EG0011 affected208 at risk EG0029 affected524 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0010 affected208 at risk EG00211 affected524 at risk
Anxiety	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0006 affected527 at risk EG0011 affected208 at risk EG00211 affected524 at risk
Insomnia	Psychiatric disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00033 affected527 at risk EG0015 affected208 at risk EG00228 affected524 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00030 affected527 at risk EG0013 affected208 at risk EG00235 affected524 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00014 affected527 at risk EG0013 affected208 at risk EG00221 affected524 at risk
Nocturia	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0011 affected208 at risk EG00216 affected524 at risk
Pollakiuria	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00019 affected527 at risk EG0015 affected208 at risk EG00221 affected524 at risk
Urinary Incontinence	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0008 affected527 at risk EG0010 affected208 at risk EG00214 affected524 at risk
Urinary Retention	Renal and urinary disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00014 affected527 at risk EG0010 affected208 at risk EG00213 affected524 at risk
Pelvic Pain	Reproductive system and breast disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00014 affected527 at risk EG0011 affected208 at risk EG00210 affected524 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00033 affected527 at risk EG0014 affected208 at risk EG00240 affected524 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00015 affected527 at risk EG0016 affected208 at risk EG00217 affected524 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0004 affected527 at risk EG0012 affected208 at risk EG00213 affected524 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0007 affected527 at risk EG0011 affected208 at risk EG00214 affected524 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0003 affected527 at risk EG0011 affected208 at risk EG00213 affected524 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0008 affected527 at risk EG0012 affected208 at risk EG00218 affected524 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0007 affected527 at risk EG0014 affected208 at risk EG00212 affected524 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0002 affected527 at risk EG0013 affected208 at risk EG00214 affected524 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00010 affected527 at risk EG0011 affected208 at risk EG00218 affected524 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00025 affected527 at risk EG00113 affected208 at risk EG00258 affected524 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00023 affected527 at risk EG00126 affected208 at risk EG002106 affected524 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA Version 23.0	Non-systematic Assessment	EG0005 affected527 at risk EG0016 affected208 at risk EG00217 affected524 at risk
Hot Flush	Vascular disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00087 affected527 at risk EG0013 affected208 at risk EG002121 affected524 at risk
Hypertension	Vascular disorders	MedDRA Version 23.0	Non-systematic Assessment	EG00084 affected527 at risk EG00113 affected208 at risk EG002100 affected524 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Homewood	Alabama		United States

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
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

ID	Title	Description
BG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
BG001	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + Androgen Deprivation Therapy (ADT)	Participants received matching placebo (4 tablets) orally once daily (qd) along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. In the event of a positive result at interim or final analysis participants in treatment phase had opportunity to receive Apalutamide +ADT. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	35	527	115	527	485	527
EG001	Placebo + ADT to Apalutamide + ADT	After interim analysis and unblinding, participants receiving placebo +ADT crossed over to receive 240 mg apalutamide orally qd along with ADT in open-label extension phase.	10	208	29	208	153	208
EG002	Apalutamide + ADT	Participants received JNJ-56021927 (apalutamide) 240 milligrams (mg) (4*60 mg tablets) orally qd along with ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration) as standard of care therapy in each 28-day treatment cycle. The choice of the GnRHa (agonist or antagonist) was at discretion of the investigator. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death.	31	524	153	524	494	524