A Study to Assess the Benefit of Treatment Beyond Progres... | NCT02288247

NCT02288247

ID	Type	Description	Link
2013-004711-50	EudraCT Number

Status Module

Name	Class
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Enzalutamide	Experimental	Participants (Pts) received OL enzalutamide 160 mg QD from Day 1 in Period 1 (P1) until they were either randomized to Period 2 (P2), were ineligible, experienced intolerable toxicity, withdrew, or died. Pts with confirmed disease progression in P1, meeting eligibility, were randomized to receive placebo/enzalutamide 160 mg QD with docetaxel 75 mg/m^2 in 1hour infusion every 3 weeks & prednisolone 5mg twice daily in P2. Docetaxel & prednisolone were administered for upto 10 cycles (1 cycle=3 weeks) or more per investigator discretion, while placebo/enzalutamide continued until progression, toxicity, withdrawal, or death. Extension(EXT) phase was available for Pts in P1& P2 who were not meeting primary endpoint. Enzalutamide continued until disease progression, intolerable toxicity, withdrawal, or death. Pts not entering EXT discontinued and received local care. Those benefiting from enzalutamide in EXT at study closure continued in study 9785-CL-0123 or via commercial enzalutamide.	Drug: Enzalutamide Drug: Docetaxel Drug: Prednisolone
Placebo	Placebo Comparator	Participants received an OL treatment with enzalutamide 160 mg capsules, orally once daily from day 1 in period 1 until randomization to period 2 treatment, confirmation of ineligibility for period 2 treatment, intolerable toxicity, withdrawal, or death, whichever occurred first. Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, DB in period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle = 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants discontinued the study and received local standard of care.	Drug: Docetaxel Drug: Prednisolone

Name	Type	Description	Arm Group Labels	Other Names
Enzalutamide	Drug	Oral	Enzalutamide	Xtandi ASP9785

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival (PFS)	PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression.	From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Time to Prostate-specific Antigen (PSA) Progression	Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
Ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of initiation of investigational medicinal product (IMP), or bilateral orchiectomy (i.e., surgical or medical castration);
Metastatic disease documented by at least 2 bone lesions on bone scan, or soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI);
Progressive disease at study entry defined as the following occurring in the setting of castrate levels of testosterone: Prostate specific antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination.
Asymptomatic or minimally symptomatic prostate cancer (Brief Pain Inventory - Short Form (BPI-SF) question 3 score of < 4);
Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
Estimated life expectancy of ≥ 12 months;
Be suitable and willing to receive chemotherapy as part of the trial;
Able to swallow the IMP and comply with study requirements;
Subject agreed not to participate in another interventional study while on treatment.

Exclusion Criteria:

Prior treatment with the following agents for the treatment of prostate cancer: Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory therapies; Cytotoxic chemotherapy; Participation in a clinical trial of an investigational agent that inhibits the AR or androgen synthesis unless the treatment was placebo;
Current or prior treatment within 4 weeks prior to initiation of investigational medicinal product (IMP) with the following agents for the treatment of prostate cancer: Antiandrogens; 5-α reductase inhibitors; Estrogens; Anabolic steroids; Drugs with antiandrogenic properties; Progestational agents;
Subject had received investigational therapy within 28 days or 5 half-lives whichever was longer, prior to initiation of IMP;
Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to initiation of IMP;
Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation of IMP;
Major surgery within 4 weeks prior to initiation of IMP;
History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months prior to Screening;
Known or suspected brain metastasis or active leptomeningeal disease;
History of another malignancy within the previous 5 years other than non-melanoma skin cancer;
Clinically significant cardiovascular disease;
Gastrointestinal disorders affecting absorption;
Medical contraindications to the use of prednisolone or docetaxel;
Allergies to any of the active ingredients or excipients in the study drugs

Name	Affiliation	Role
Medical Director	Astellas Pharma Europe Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site AT43004		Linz		4010	Austria
Site AT43001

PubMed Identifier	Type	Citation	Retractions
36265504	Derived	Merseburger AS, Attard G, Astrom L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, Lopez-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. doi: 10.1016/S1470-2045(22)00560-5. Epub 2022 Oct 18.

Label	URL
Link to plain language summary of the study on the Trial Results Summaries website	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Enzalutamide	Participants received OL enzalutamide 160 milligrams (mg) capsules orally once daily (QD) from Day 1 in Period (P) 1 until they were either randomized to P2 treatment, deemed ineligible, experienced intolerable toxicity, withdrew, or died, whichever came first. Participants with confirmed disease progression on enzalutamide in Period 1 who continued to meet eligibility criteria, were randomized to receive either placebo or enzalutamide 160 mg capsules orally QD with docetaxel 75 milligrams per meter square (mg/m^2) in 1-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily in DB P2. Docetaxel and prednisolone were administered for up to 10 cycles (1 cycle = 3 weeks) or additional cycles as determined by investigator, while placebo/enzalutamide was continued until disease progression, intolerable toxicity, withdrawal, or death whichever occurred first. An Extension (EXT) phase was available for participants still in P1 and participants in P2 not meeting the primary endpoint, when the data cut-off for analysis was reached. Treatment with enzalutamide continued until the disease progression, intolerable toxicity, participant withdrawal or death. Participants who did not enter EXT phase had discontinued study and received local standard of care treatment. Those who were still benefiting from enzalutamide treatment in EXT phase at study closure continued enzalutamide therapy in another Astellas-sponsored study 9785-CL-0123 or via commercially available enzalutamide.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 1, 2022	Dec 19, 2024

Arm/Group Information

ID	Title	Description
BG000	Enzalutamide	Participants received OL enzalutamide 160 mg capsules orally QD from Day 1 in Period 1 until they were either randomized to Period 2 treatment, deemed ineligible, experienced intolerable toxicity, withdrew, or died, whichever came first. Participants with confirmed disease progression on enzalutamide in Period 1, who continued to meet eligibility criteria, were randomized to receive either placebo or enzalutamide 160 mg capsules orally QD with docetaxel 75 mg/m^2 in 1-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily in DB Period 2. Docetaxel and prednisolone were administered for up to 10 cycles (1 cycle = 3 weeks) or additional cycles as determined by investigator, while placebo/enzalutamide was continued until disease progression, intolerable toxicity, withdrawal, or death whichever occurred first. An EXT was available for patients still in P1 and patients in P2 not meeting the primary endpoint, when the data cut-off for analysis was reached. Treatment with enzalutamide continued until the disease progression, intolerable toxicity, participant withdrawal or death. Participants who did not enter extension phase had discontinued study and received local standard of care treatment. Those who were still benefiting from enzalutamide treatment in EXT phase at study closure continued enzalutamide therapy in another Astellas-sponsored study 9785-CL-0123 or via commercially available enzalutamide.

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

Progression Free Survival (PFS)

PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression.

The Full Analysis Set (FAS) consisted of all participants who were randomized and received at least one dose of IMP.

Posted

Median

95% Confidence Interval

months

From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001	Placebo	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Units	Counts
Participants	OG000136 OG001135

Title

Denominators

Categories

Title	Measurements
	OG0009.53(8.25 to 10.87) OG0018.28(6.28 to 8.71)

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		Cox proportional hazards model		0.027	From the Cox proportional hazards model with covariates for treatment and disease progression in Period 1 (radiographic, nonradiographic).	Hazard Ratio (HR)	0.72			2-Sided	95	0.53	0.96					Superiority

Secondary

Time to Prostate-specific Antigen (PSA) Progression

Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later.

FAS

Posted

Median

95% Confidence Interval

months

From date of randomization to the first PSA value (median duration: 35 weeks)

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001

Secondary

Prostate-specific Antigen (PSA) Response

PSA response, defined as a decrease in percentage change from randomization (Period 2 Week 1) of 50% or more. PSA response was derived at Week 13 and at any time after randomization in Period 2. PSA response at any time is defined as a decrease in percentage change from randomization (Period 2 Week 1) at any time after randomization of 50% or more. Percentage of participants with PSA response was reported.

FAS

Posted

Number

percentage of participants

Randomization, Week 13, any time after randomization in Period 2 (median of 35 weeks)

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001

Secondary

Objective Response Rate (ORR)

ORR, defined as the best overall radiographic response after randomization (Period 2 Week 1) as per Investigator assessments of response for soft tissue disease per RECIST 1.1, in participants who had a measurable tumor. ORR was reported as the percentage of participants with complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

FAS

Posted

Number

percentage of participants

From date of randomization up to median duration of 35 weeks

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Secondary

Time to Pain Progression

The time to an increase of >=30% from randomization (Period 2 Week 1) in average BPI-SF item scores (items 3, 4, 5, 6) at two consecutive evaluations >=3 weeks apart without decrease in analgesic score according to the World health Organization (WHO). Only participants with an average pain intensity item score >=4 were considered. The BPI-SF was an instrument to document pain-related functional impairment and contains 7 questions which included pain intensity [(items 3, 4, 5 and 6): worst pain, least pain, average pain and current pain, with scales from 0 (no pain) to 10 (pain as bad as you can imagine)] and pain interference ](items 9A to 9G): general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life, with scales from 0 (does not interfere) to 10 (completely interferes)]. The BPI-SF total score for pain intensity was calculated as the mean of the 4 scores for the 4 items of pain intensity.

Data was not estimable as none of the participants met the criteria for pain progression

Posted

From date of randomization up to median duration of 35 weeks

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Secondary

Time to Opiate Use for Cancer-related Pain

Time to opiate use for cancer-related pain, defined as the time from randomization (Period 2 Week 1) to initiation of chronic administration of opiate analgesia [parenteral opiate use for ≥7 days or use of WHO Analgesic Ladder Level 3 oral opiates for ≥3 weeks].

Data was not estimable as none of the participants had cancer-related pain.

Posted

From date of randomization up to median duration of 35 weeks

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001	Placebo	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Secondary

Time to First Skeletal-related Event (SRE)

Time to first SRE, defined as the time from randomization (Period 2 Week 1) to radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain.

FAS

Posted

Median

95% Confidence Interval

months

From date of randomization up to median duration of 35 weeks

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001	Placebo	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Secondary

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)

FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life.

Participants in the FAS population with available data were analyzed.

Posted

Mean

Standard Deviation

score on a scale

Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.

Secondary

Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)

The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable).

Participants in the FAS population with available data were analyzed.

Posted

Mean

Standard Deviation

score on a scale

Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

ID	Title	Description
OG000	Enzalutamide	Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, in DB treatment period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants could continue the extension period if they were still receiving study drug in Period 1 when enrollment to Period 2 closed or when the data cut-off for analysis was reached in Period 2, until the investigator or participant decided to stop or disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.
OG001	Placebo

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Period 1: Enzalutamide	Participants received OL enzalutamide 160 mg capsules orally QD from Day 1 in Period 1 until they were either randomized to Period 2 treatment, deemed ineligible, experienced intolerable toxicity, withdrew, or died, whichever came first. An EXT phase was available for participants still in P1 not meeting the primary endpoint, when the data cut-off for analysis was reached. Treatment with enzalutamide continued until the disease progression, intolerable toxicity, participant withdrawal or death. Participants who did not enter EXT phase had discontinued study and received local standard of care treatment. Those who were still benefiting from enzalutamide treatment in EXT phase at study closure continued enzalutamide therapy in another Astellas-sponsored study 9785-CL-0123 or via commercially available enzalutamide.	51	687	238	687	523	687
EG001	Period 2: Enzalutamide	Participants with confirmed disease progression on enzalutamide in P1 and who continued to meet all eligibility criteria received enzalutamide 160 mg capsules, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, DB treatment in P2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. An EXT was available for participants in P2 not meeting the primary endpoint, when the data cut-off for analysis was reached. Treatment with enzalutamide continued until the disease progression, intolerable toxicity, participant withdrawal or death. Participants who did not enter EXT phase had discontinued study and received local standard of care treatment. Those who were still benefiting from enzalutamide treatment in EXT phase at study closure continued enzalutamide therapy in another Astellas-sponsored study 9785-CL-0123 or via commercially available enzalutamide.	18	136	67	136	125	136
EG002	Period 2: Placebo	Participants with confirmed disease progression on enzalutamide in P1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, DB in P2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle= 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first.	15	135	52	135	123	135

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG00017 events9 affected687 at risk EG0013 events3 affected136 at risk EG0022 events2 affected135 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG00110 events10 affected136 at risk EG00217 events15 affected135 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0013 events2 affected136 at risk EG0021 events1 affected135 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG00121 events11 affected136 at risk EG00212 events5 affected135 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Angina pectoris	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Arrhythmia	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG00014 events12 affected687 at risk EG0013 events3 affected136 at risk EG0022 events2 affected135 at risk
Atrial flutter	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Atrioventricular block	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cardiac arrest	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Cardiac failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0006 events6 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Cardiac failure acute	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cardiogenic shock	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Coronary artery disease	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dressler's syndrome	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Left ventricular failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG00010 events9 affected687 at risk EG0012 events2 affected136 at risk EG0020 events0 affected135 at risk
Palpitations	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Stress cardiomyopathy	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Vertigo	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Goitre	Endocrine disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Blindness	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Exfoliation glaucoma	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Retinal detachment	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Vision blurred	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0022 events1 affected135 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Ascites	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Constipation	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0022 events2 affected135 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0023 events3 affected135 at risk
Duodenal ulcer perforation	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Ileus	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0007 events5 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Mechanical ileus	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Nausea	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0022 events2 affected135 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0013 events1 affected136 at risk EG0020 events0 affected135 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0012 events2 affected136 at risk EG0021 events1 affected135 at risk
Asthenia	General disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0012 events2 affected136 at risk EG0020 events0 affected135 at risk
Chest pain	General disorders	MedDRA v23.0	Systematic Assessment	EG0005 events4 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Chills	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Death	General disorders	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Fatigue	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Gait disturbance	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
General physical health deterioration	General disorders	MedDRA v23.0	Systematic Assessment	EG0006 events5 affected687 at risk EG0011 events1 affected136 at risk EG0024 events3 affected135 at risk
Generalised oedema	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0012 events1 affected136 at risk EG0021 events1 affected135 at risk
Hypothermia	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Malaise	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Pain	General disorders	MedDRA v23.0	Systematic Assessment	EG0006 events5 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pyrexia	General disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0017 events6 affected136 at risk EG0022 events2 affected135 at risk
Sudden death	General disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Drug hypersensitivity	Immune system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Bronchitis bacterial	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Catheter bacteraemia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Cellulitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dacryocystitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Device related infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Diverticulitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Erysipelas	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Infective aneurysm	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Influenza	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Klebsiella sepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0013 events2 affected136 at risk EG0020 events0 affected135 at risk
Lyme disease	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Meningitis bacterial	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Neutropenic sepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0016 events5 affected136 at risk EG0023 events3 affected135 at risk
Peritonitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG0014 events4 affected136 at risk EG0023 events3 affected135 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Respiratory tract infection fungal	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Sepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG0012 events2 affected136 at risk EG0020 events0 affected135 at risk
Septic shock	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0013 events3 affected136 at risk EG0020 events0 affected135 at risk
Streptococcal urinary tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Urinary tract infection pseudomonal	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urosepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0007 events6 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0009 events8 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0007 events6 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Incorrect dose administered	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Injury	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Medication error	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urinary tract stoma complication	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urostomy complication	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Alanine aminotransferase increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Blood bilirubin increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Eastern Cooperative Oncology Group performance status worsened	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
General physical condition abnormal	Investigations	MedDRA v23.0	Systematic Assessment	EG0008 events5 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Haemoglobin decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Liver function test increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Neutrophil count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0013 events2 affected136 at risk EG0021 events1 affected135 at risk
Platelet count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Troponin I increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0003 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00014 events12 affected687 at risk EG0012 events2 affected136 at risk EG0024 events3 affected135 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0012 events1 affected136 at risk EG0021 events1 affected135 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0003 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0005 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bladder transitional cell carcinoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected687 at risk EG0012 events2 affected136 at risk EG0021 events1 affected135 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Intestinal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lip neoplasm malignant stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Liposarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Malignant neoplasm of pleura	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG00024 events22 affected687 at risk EG0016 events6 affected136 at risk EG0026 events6 affected135 at risk
Malignant peritoneal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Myeloproliferative neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Soft tissue sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Uveal melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Amnesia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Amyotrophic lateral sclerosis	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Aphasia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Ataxia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Brain compression	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dizziness	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Epilepsy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Headache	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hemiplegia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypertensive encephalopathy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Ischaemic stroke	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Motor dysfunction	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Paraesthesia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Paraplegia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Parkinson's disease	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Polyneuropathy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Presyncope	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Sciatica	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Seizure	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Spinal cord compression	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0006 events6 affected687 at risk EG0015 events5 affected136 at risk EG0021 events1 affected135 at risk
Syncope	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Vascular dementia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Device dislocation	Product Issues	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Thrombosis in device	Product Issues	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Confusional state	Psychiatric disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hallucination	Psychiatric disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0008 events7 affected687 at risk EG0012 events2 affected136 at risk EG0022 events2 affected135 at risk
Bladder outlet obstruction	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bladder tamponade	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Haematuria	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG00017 events12 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0007 events6 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urethral obstruction	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urethral stenosis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Urinary bladder polyp	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urinary retention	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0007 events7 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Urinary tract disorder	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Scrotal pain	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG00011 events8 affected687 at risk EG0012 events2 affected136 at risk EG0021 events1 affected135 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0012 events2 affected136 at risk EG0020 events0 affected135 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Bone operation	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Cardiac pacemaker removal	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Carpal tunnel decompression	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Catheterisation venous	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Arterial insufficiency	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Circulatory collapse	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Deep vein thrombosis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Haematoma	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypertensive crisis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Hypotension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Malignant hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Orthostatic hypotension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0010 events0 affected136 at risk EG0021 events1 affected135 at risk
Shock haemorrhagic	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0011 events1 affected136 at risk EG0020 events0 affected135 at risk
Thrombosis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk
Venous thrombosis limb	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG0010 events0 affected136 at risk EG0020 events0 affected135 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG00063 events49 affected687 at risk EG00147 events27 affected136 at risk EG00232 events15 affected135 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG00137 events11 affected136 at risk EG00248 events16 affected135 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected687 at risk EG001125 events41 affected136 at risk EG002129 events43 affected135 at risk
Lacrimation increased	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0003 events2 affected687 at risk EG00128 events25 affected136 at risk EG0027 events6 affected135 at risk
Constipation	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG00064 events60 affected687 at risk EG00121 events12 affected136 at risk EG00217 events15 affected135 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG00077 events63 affected687 at risk EG00151 events37 affected136 at risk EG00267 events42 affected135 at risk
Nausea	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG00079 events69 affected687 at risk EG00133 events26 affected136 at risk EG00231 events25 affected135 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG0015 events5 affected136 at risk EG0029 events8 affected135 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG00025 events22 affected687 at risk EG0018 events8 affected136 at risk EG0026 events6 affected135 at risk
Asthenia	General disorders	MedDRA v23.0	Systematic Assessment	EG000175 events109 affected687 at risk EG00194 events46 affected136 at risk EG00264 events35 affected135 at risk
Fatigue	General disorders	MedDRA v23.0	Systematic Assessment	EG000194 events159 affected687 at risk EG00165 events40 affected136 at risk EG00241 events28 affected135 at risk
Mucosal inflammation	General disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected687 at risk EG00114 events10 affected136 at risk EG00219 events17 affected135 at risk
Oedema peripheral	General disorders	MedDRA v23.0	Systematic Assessment	EG00031 events26 affected687 at risk EG00118 events16 affected136 at risk EG00223 events20 affected135 at risk
Pyrexia	General disorders	MedDRA v23.0	Systematic Assessment	EG00019 events18 affected687 at risk EG00111 events9 affected136 at risk EG0029 events7 affected135 at risk
Nasopharyngitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG00033 events28 affected687 at risk EG0015 events4 affected136 at risk EG0028 events8 affected135 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG00064 events47 affected687 at risk EG0017 events6 affected136 at risk EG0024 events4 affected135 at risk
Haemoglobin decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG00017 events15 affected687 at risk EG0013 events2 affected136 at risk EG0027 events7 affected135 at risk
Neutrophil count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected687 at risk EG00114 events7 affected136 at risk EG00227 events7 affected135 at risk
Weight decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG00036 events30 affected687 at risk EG00111 events11 affected136 at risk EG0022 events2 affected135 at risk
White blood cell count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG00012 events9 affected687 at risk EG00117 events5 affected136 at risk EG00224 events7 affected135 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG00086 events69 affected687 at risk EG00128 events23 affected136 at risk EG00218 events17 affected135 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00085 events70 affected687 at risk EG00127 events25 affected136 at risk EG00210 events10 affected135 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG000153 events117 affected687 at risk EG00115 events13 affected136 at risk EG00215 events14 affected135 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00080 events64 affected687 at risk EG00114 events12 affected136 at risk EG00216 events14 affected135 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00038 events33 affected687 at risk EG0017 events5 affected136 at risk EG00212 events7 affected135 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00023 events22 affected687 at risk EG0019 events9 affected136 at risk EG0029 events7 affected135 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG00055 events44 affected687 at risk EG00110 events7 affected136 at risk EG0027 events7 affected135 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG00026 events23 affected687 at risk EG00112 events8 affected136 at risk EG00214 events11 affected135 at risk
Dizziness	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG00049 events45 affected687 at risk EG0015 events5 affected136 at risk EG0026 events6 affected135 at risk
Dysgeusia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG00012 events10 affected687 at risk EG00122 events18 affected136 at risk EG0029 events9 affected135 at risk
Headache	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG00056 events44 affected687 at risk EG0016 events5 affected136 at risk EG00210 events8 affected135 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG00129 events22 affected136 at risk EG00221 events12 affected135 at risk
Paraesthesia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG00024 events22 affected687 at risk EG00110 events8 affected136 at risk EG00221 events10 affected135 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected687 at risk EG00116 events12 affected136 at risk EG00225 events14 affected135 at risk
Taste disorder	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0007 events7 affected687 at risk EG0016 events6 affected136 at risk EG00211 events9 affected135 at risk
Haematuria	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG00050 events41 affected687 at risk EG0015 events4 affected136 at risk EG0028 events7 affected135 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG00032 events27 affected687 at risk EG00115 events11 affected136 at risk EG00211 events10 affected135 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG00030 events28 affected687 at risk EG00113 events11 affected136 at risk EG0024 events4 affected135 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG00011 events10 affected687 at risk EG00116 events13 affected136 at risk EG0029 events7 affected135 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected687 at risk EG00156 events44 affected136 at risk EG00248 events37 affected135 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG00014 events14 affected687 at risk EG00112 events12 affected136 at risk EG0025 events5 affected135 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG00113 events13 affected136 at risk EG0028 events7 affected135 at risk
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG0019 events7 affected136 at risk EG0023 events2 affected135 at risk
Nail toxicity	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG00116 events11 affected136 at risk EG0027 events5 affected135 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG00114 events13 affected136 at risk EG00216 events12 affected135 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected687 at risk EG00115 events10 affected136 at risk EG0021 events1 affected135 at risk
Hot flush	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG00089 events73 affected687 at risk EG0011 events1 affected136 at risk EG0021 events1 affected135 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG000103 events91 affected687 at risk EG0015 events3 affected136 at risk EG0022 events2 affected135 at risk

ID	Term
D009362	Neoplasm Metastasis
D011471	Prostatic Neoplasms

ID	Term
D009385	Neoplastic Processes
D009369	Neoplasms
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds