Trial Outcomes & Findings for A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer (NCT NCT01288911)

NCT ID: NCT01288911

Last Updated: 2024-12-06

Results Overview

PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 375 participants
• Primary outcome timeframe: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
• Results posted on: 2024-12-06

Participant Flow

Men with metastatic castration-resistant prostate cancer (mCRPC) were enrolled at 84 sites in a total of 8 countries.

Participants were stratified by whether bilateral orchiectomy or receipt of luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy started before or after the diagnosis of metastases and by site.

Participant milestones

Measure	Enzalutamide Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Double-blind Period STARTED	184	191
Double-blind Period Received Treatment	183	189
Double-blind Period COMPLETED	42	9
Double-blind Period NOT COMPLETED	142	182
Open-label Period (All Enzalutamide) STARTED	42	9
Open-label Period (All Enzalutamide) Received Treatment	42	9
Open-label Period (All Enzalutamide) COMPLETED	0	0
Open-label Period (All Enzalutamide) NOT COMPLETED	42	9

Reasons for withdrawal

Measure	Enzalutamide Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Double-blind Period Death	11	7
Double-blind Period Lost to Follow-up	0	2
Double-blind Period Progressive Disease	75	103
Double-blind Period Protocol Violation	1	0
Double-blind Period Withdrawal by Subject	25	26
Double-blind Period Miscellaneous Reason	29	42
Double-blind Period Randomized but never received study drug	1	2
Open-label Period (All Enzalutamide) Death	0	1
Open-label Period (All Enzalutamide) Lost to Follow-up	1	0
Open-label Period (All Enzalutamide) Progressive disease	18	3
Open-label Period (All Enzalutamide) Withdrawal by Subject	1	0
Open-label Period (All Enzalutamide) Miscellaneous Reason	5	0
Open-label Period (All Enzalutamide) Transitioned to 9785-CL-0123 NCT02960022	17	5

Baseline Characteristics

A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

Baseline characteristics by cohort

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total n=375 Participants Total of all reporting groups
Age, Continuous	70.3 years STANDARD_DEVIATION 9.22 • n=5 Participants	71.1 years STANDARD_DEVIATION 8.89 • n=7 Participants	70.7 years STANDARD_DEVIATION 9.05 • n=5 Participants
Age, Customized < 65 years	45 participants n=5 Participants	47 participants n=7 Participants	92 participants n=5 Participants
Age, Customized 65-75 years	85 participants n=5 Participants	80 participants n=7 Participants	165 participants n=5 Participants
Age, Customized > 75 years	54 participants n=5 Participants	64 participants n=7 Participants	118 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	184 Participants n=5 Participants	191 Participants n=7 Participants	375 Participants n=5 Participants
Race/Ethnicity, Customized White	172 Participants n=5 Participants	176 Participants n=7 Participants	348 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity Not Hispanic or Latino	184 Participants n=5 Participants	187 Participants n=7 Participants	371 Participants n=5 Participants
Ethnicity Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
LHRH agonist/antagonist initiation or bilateral orchiectomy relative to diagnosis of metastasis Before diagnosis of metastasis	87 Participants n=5 Participants	76 Participants n=7 Participants	163 Participants n=5 Participants
LHRH agonist/antagonist initiation or bilateral orchiectomy relative to diagnosis of metastasis After diagnosis of metastasis	97 Participants n=5 Participants	115 Participants n=7 Participants	212 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set (all randomized participants)

PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment	15.7 months Interval 11.5 to 19.4	5.8 months Interval 4.8 to 8.1	—

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

PFS was calculated as the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by investigators, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
PFS Based on Investigator Assessment	15.3 months Interval 11.8 to 19.4	5.7 months Interval 5.4 to 8.1	—

SECONDARY outcome

Timeframe: Baseline to Week 13

Population: Full analysis set with available PSA data

The PSA response by Week 13 was defined as the percentage change from Baseline to the smallest PSA value after Baseline (i.e., a decrease of 100% represents the largest possible decrease to a value below the lower limit of quantification) and on or before day 99 (i.e., upper boundary of the Week 13 visit window). For participants with no decrease in PSA post-baseline by Week 13, the PSA response by Week 13 was the smallest increase in PSA up to day 99. For participants with no post-baseline PSA values up to day 99, the PSA response by Week 13 was set to missing. PSA was analyzed at a central laboratory.

Outcome measures

Measure	Enzalutamide n=171 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=163 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Prostate-specific Antigen (PSA) Response by Week 13	-89.03 percent change Interval -100.0 to 287.7	0.36 percent change Interval -98.5 to 25700.0	—

SECONDARY outcome

Timeframe: Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set with available PSA data

The best PSA response was defined as the percentage change from Baseline to the smallest PSA value after Baseline including PSA results from samples taken after the study drug was stopped. For participants with no decrease in PSA post-baseline, the best PSA response was the smallest increase in PSA. For participants with no post-baseline PSA values, the PSA response was set to missing. PSA was analyzed at a central laboratory.

Outcome measures

Measure	Enzalutamide n=174 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=168 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Best PSA Response	-92.96 percent change Interval -100.0 to 287.7	0.18 percent change Interval -99.8 to 25700.0	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

Time to PSA progression was calculated as the time interval from the date of randomization to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline value for participants who did not have a decline in PSA post-baseline values), and confirmed by a second consecutive PSA assessment at least 3 weeks later. For participants with no documented PSA progression, the time to PSA progression was censored on the date the last PSA sample was taken.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Time to PSA Progression	19.4 months Interval 16.6 to Not reached due to the low number of events	5.8 months Interval 5.6 to 8.3	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

Time to PSA ≤ 4 ng/mL was defined as the time interval from the date of randomization to the first date a decline in PSA to a result of 4 ng/mL or below was recorded. In participants without PSA results ≤ 4 ng/mL, the time to PSA ≤ 4 ng/mL was censored on the date of the last PSA sample taken. Participants with a PSA result ≤ 4 ng/mL at Baseline, participants with no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Time to PSA ≤ 4 ng/mL	3.0 months Interval 2.9 to 5.6	NA months Not reached due to the low number of events	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

The time to ≥ 30% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 30% was recorded. In participants without ≥ 30% PSA decline from Baseline, the time to ≥ 30% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Time to ≥ 30% PSA Decline From Baseline	2.8 months Interval 2.8 to 2.8	NA months Not reached due to the low number of events	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

The time to ≥ 50% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 50% was recorded. In participants without ≥ 50% PSA decline from Baseline, the time to ≥ 50% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Time to ≥ 50% PSA Decline From Baseline	2.8 months Interval 2.8 to 2.8	NA months Not reached due to the low number of events	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

The time to ≥ 90% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 90% was recorded. In participants without ≥ 90% PSA decline from Baseline, the time to ≥ 90% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Time to ≥ 90% PSA Decline From Baseline	5.4 months Interval 3.0 to 5.7	NA months Not reached due to the low number of events	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

Radiographic PFS was calculated as the time interval from the date of randomization to the first date of radiographic disease progression. Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions (a minimum of 2 new bone lesions as compared to previous scan) on bone scan and confirmed by the next bone scan.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Radiographic PFS Based on ICR Assessment	NA months Interval 25.6 to Not reached due to the low number of events	16.4 months Interval 11.1 to 18.1	—

SECONDARY outcome

Timeframe: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.

Population: Full analysis set

Response assessments were reported by ICR for target lesions in soft tissues and non-target lesions in soft tissues based on CT and/or MRI according to RECIST version 1.1. Objective response was defined as the number of participants achieving either a complete response (CR) or a partial response (PR) based on participant's best overall response assessed at the end of the treatment.

Outcome measures

Measure	Enzalutamide n=184 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=191 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Percentage of Participants With an Objective Response	15.8 percentage of participants	2.6 percentage of participants	—

SECONDARY outcome

Timeframe: From initiation of study drug up to 30 days after last dose of study drug or the 30-day safety follow-up visit, whichever was last (Median duration of treatment was 11.6 months in enzalutamide arm and 5.8 in bicalutamide arm, 12.6 in the total arm).

Population: Safety Analysis Set (all participants who had initiated at least 1 dose of study drug)

A serious adverse event was defined as any untoward medical occurrence that at any dose: ● Resulted in death ● Was life threatening ● Resulted in persistent or significant disability/incapacity ● Resulted in congenital anomaly or birth defect ● Required inpatient hospitalization or led to prolongation of hospitalization ● Other medically important events. Treatment-related indicates adverse events assessed by the Investigator as probably or possibly related to study treatment. Treatment emergent adverse events (TEAEs) were defined as adverse events (AEs) that started or worsened after starting administration of study drug through end of the study (i.e., the treatment-emergent period).

Outcome measures

Measure	Enzalutamide n=183 Participants Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Bicalutamide n=189 Participants Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Total Enzalutamide n=192 Participants Participants received enzalutamide in the double-blind and/or open-label period (including participants who switched from bicalutamide to enzalutamide).
Percentage of Participants With Adverse Events Serious TEAEs	33.3 percentage of participants	23.8 percentage of participants	36.5 percentage of participants
Percentage of Participants With Adverse Events Drug regimen-related serious TEAEs	6.6 percentage of participants	3.2 percentage of participants	6.8 percentage of participants
Percentage of Participants With Adverse Events TEAEs	94.5 percentage of participants	94.2 percentage of participants	94.8 percentage of participants
Percentage of Participants With Adverse Events Related TEAEs	66.7 percentage of participants	49.7 percentage of participants	67.2 percentage of participants
Percentage of Participants With Adverse Events Deaths	5.5 percentage of participants	1.6 percentage of participants	5.7 percentage of participants
Percentage of Participants With Adverse Events TEAEs leading to discontinuation	29.5 percentage of participants	23.8 percentage of participants	31.3 percentage of participants
Percentage of Participants With Adverse Events Drug regimen-related TEAEs leading to discon.	7.7 percentage of participants	5.3 percentage of participants	7.8 percentage of participants
Percentage of Participants With Adverse Events TEAEs leading to study drug interruption	10.4 percentage of participants	7.9 percentage of participants	10.4 percentage of participants

Adverse Events

Double-blind Period: Enzalutamide

Serious events: 49 serious events

Other events: 123 other events

Deaths: 11 deaths

Double-blind Period: Bicalutamide

Serious events: 43 serious events

Other events: 149 other events

Deaths: 7 deaths

Open-label Period: Enzalutamide/Enzalutamide

Serious events: 18 serious events

Other events: 42 other events

Deaths: 0 deaths

Open-label Period: Bicalutamide/Enzalutamide

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Measure	Double-blind Period: Enzalutamide n=141 participants at risk Participants received enzalutamide 160 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Double-blind Period: Bicalutamide n=180 participants at risk Participants received bicalutamide 50 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Open-label Period: Enzalutamide/Enzalutamide n=42 participants at risk Participants received enzalutamide in the double-blind period and received enzalutamide in the open-label period as well.	Open-label Period: Bicalutamide/Enzalutamide n=9 participants at risk Participants received bicalutamide in the double-blind period and switched over to enzalutamide in the open-label period.
Blood and lymphatic system disorders Anaemia	3.5% 5/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Blood and lymphatic system disorders Pancytopenia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Acute myocardial infarction	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Angina pectoris	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Aortic valve stenosis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Atrial fibrillation	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Atrioventricular block	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Atrioventricular block complete	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Bradycardia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Cardiac failure congestive	2.1% 3/141 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.7% 3/180 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Cardiogenic shock	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Coronary artery disease	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Mitral valve incompetence	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Myocardial infarction	2.8% 4/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Sick sinus syndrome	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Sinus tachycardia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Supraventricular tachycardia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Ventricular extrasystoles	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Ventricular fibrillation	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Ventricular tachyarrhythmia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Congenital, familial and genetic disorders Arteriovenous malformation	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Abdominal pain	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Constipation	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Diarrhoea	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Diverticulum	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Haematemesis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Haematochezia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Rectal haemorrhage	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Salivary gland calculus	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Vomiting	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Asthenia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Fatigue	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders General physical health deterioration	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Generalised oedema	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Non-cardiac chest pain	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Pain	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Pyrexia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Systemic inflammatory response syndrome	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Hepatobiliary disorders Cholelithiasis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Abscess of salivary gland	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Arthritis bacterial	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Bacteraemia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Cellulitis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal colic	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Cystitis	0.71% 1/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Diverticulitis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Gastroenteritis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Gastroenteritis viral	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Infection	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Pneumonia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Urosepsis	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Craniocerebral injury	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Fall	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Hip fracture	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Rib fracture	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Alanine aminotransferase increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Arteriogram coronary	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Aspartate aminotransferase increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Blood creatinine increased	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Eastern Cooperative Oncology Group performance status worsened	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Gamma-glutamyltransferase increased	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Liver function test abnormal	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Dehydration	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Back pain	0.71% 1/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Joint lock	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Muscular weakness	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Pathological fracture	3.5% 5/141 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.71% 1/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal failure	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basosquamous carcinoma of skin	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm malignant	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of conjunctiva	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraneoplastic syndrome	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penile cancer	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Superficial spreading melanoma stage unspecified	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Convulsion	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Epiduritis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Hypoglycaemic seizure	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Incoherent	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Lacunar infarction	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Paraplegia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Presyncope	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Spinal cord compression	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Syncope	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Transient ischaemic attack	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Tremor	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Acute prerenal failure	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Bladder obstruction	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Bladder outlet obstruction	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Dysuria	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Haematuria	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Hydronephrosis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Obstructive uropathy	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Postrenal failure	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal failure acute	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal impairment	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Stress urinary incontinence	0.71% 1/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Ureteric dilatation	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Urethral obstruction	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Urinary retention	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Urinary tract obstruction	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Reproductive system and breast disorders Prostatic obstruction	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Surgical and medical procedures Transurethral prostatectomy	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Aortic stenosis	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Hypotension	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Orthostatic hypotension	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Peripheral artery stenosis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Venous thrombosis limb	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.

Other adverse events

Measure	Double-blind Period: Enzalutamide n=141 participants at risk Participants received enzalutamide 160 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Double-blind Period: Bicalutamide n=180 participants at risk Participants received bicalutamide 50 mg orally once daily in the double-blind period until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.	Open-label Period: Enzalutamide/Enzalutamide n=42 participants at risk Participants received enzalutamide in the double-blind period and received enzalutamide in the open-label period as well.	Open-label Period: Bicalutamide/Enzalutamide n=9 participants at risk Participants received bicalutamide in the double-blind period and switched over to enzalutamide in the open-label period.
Blood and lymphatic system disorders Anaemia	7.1% 10/141 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.8% 5/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Angina pectoris	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Cardiac disorders Palpitations	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Eye disorders Cataract	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Eye disorders Glaucoma	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Eye disorders Ocular hyperaemia	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Abdominal pain	4.3% 6/141 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.9% 7/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Constipation	13.5% 19/141 • Number of events 21 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	13.3% 24/180 • Number of events 25 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Diarrhoea	11.3% 16/141 • Number of events 18 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	8.3% 15/180 • Number of events 18 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	22.2% 2/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Dyspepsia	3.5% 5/141 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.2% 4/180 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	22.2% 2/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Haemorrhoids	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Nausea	12.8% 18/141 • Number of events 22 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	18.3% 33/180 • Number of events 36 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	23.8% 10/42 • Number of events 11 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Rectal haemorrhage	2.8% 4/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Gastrointestinal disorders Vomiting	3.5% 5/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	5.0% 9/180 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Asthenia	5.7% 8/141 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.9% 7/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Fatigue	24.8% 35/141 • Number of events 40 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	21.1% 38/180 • Number of events 45 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	42.9% 18/42 • Number of events 24 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	33.3% 3/9 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Oedema peripheral	7.1% 10/141 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.2% 13/180 • Number of events 13 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
General disorders Pain	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.4% 8/180 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Bronchitis	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Influenza	2.1% 3/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.2% 4/180 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Nasopharyngitis	7.8% 11/141 • Number of events 13 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.9% 7/180 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	16.7% 7/42 • Number of events 9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Osteomyelitis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Scrotal infection	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Infections and infestations Urinary tract infection	5.0% 7/141 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.7% 3/180 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Fall	6.4% 9/141 • Number of events 11 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.3% 6/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	22.2% 2/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Injury, poisoning and procedural complications Rib fracture	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Blood alkaline phosphatase increased	2.1% 3/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.8% 5/180 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Blood urea increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.7% 3/180 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Haematocrit decreased	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Haemoglobin decreased	2.1% 3/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.8% 5/180 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Neutrophil count increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Prostatic specific antigen increased	2.8% 4/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Red blood cell count increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations Weight decreased	11.3% 16/141 • Number of events 19 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	8.3% 15/180 • Number of events 15 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Investigations White blood cell count increased	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Decreased appetite	11.3% 16/141 • Number of events 19 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.2% 13/180 • Number of events 13 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hypercholesterolaemia	2.1% 3/141 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hyperglycaemia	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hyperkalaemia	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Metabolism and nutrition disorders Hypokalaemia	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.7% 3/180 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Arthralgia	11.3% 16/141 • Number of events 22 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	15.0% 27/180 • Number of events 39 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	21.4% 9/42 • Number of events 11 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	55.6% 5/9 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Back pain	20.6% 29/141 • Number of events 39 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	18.9% 34/180 • Number of events 40 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	26.2% 11/42 • Number of events 15 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Bone pain	7.1% 10/141 • Number of events 13 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	6.7% 12/180 • Number of events 15 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Flank pain	3.5% 5/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	4.3% 6/141 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.2% 4/180 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.7% 8/141 • Number of events 9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.4% 17/180 • Number of events 23 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Myalgia	6.4% 9/141 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.8% 5/180 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Neck pain	1.4% 2/141 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Musculoskeletal and connective tissue disorders Pain in extremity	11.3% 16/141 • Number of events 22 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	5.0% 9/180 • Number of events 12 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Amnesia	2.8% 4/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Dizziness	8.5% 12/141 • Number of events 15 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	8.3% 15/180 • Number of events 16 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	14.3% 6/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	22.2% 2/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Headache	7.8% 11/141 • Number of events 14 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.3% 6/180 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	19.0% 8/42 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	33.3% 3/9 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Lethargy	3.5% 5/141 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.2% 4/180 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Parkinson's disease	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Poor quality sleep	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Nervous system disorders Syncope	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Psychiatric disorders Depressed mood	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Psychiatric disorders Insomnia	6.4% 9/141 • Number of events 9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.4% 8/180 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Dysuria	3.5% 5/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.2% 4/180 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Haematuria	2.1% 3/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.3% 6/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.9% 5/42 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Hypertonic bladder	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Pollakiuria	5.0% 7/141 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	3.3% 6/180 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal failure chronic	1.4% 2/141 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Renal pain	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.1% 3/42 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Renal and urinary disorders Urinary retention	2.8% 4/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.8% 5/180 • Number of events 7 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Reproductive system and breast disorders Gynaecomastia	2.8% 4/141 • Number of events 4 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	14.3% 6/42 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Reproductive system and breast disorders Testicular pain	3.5% 5/141 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Cough	3.5% 5/141 • Number of events 6 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.4% 8/180 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	4.8% 2/42 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 7/141 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	5.0% 9/180 • Number of events 10 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.5% 4/42 • Number of events 8 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.4% 2/141 • Number of events 3 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.56% 1/180 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Skin and subcutaneous tissue disorders Skin lesion	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Surgical and medical procedures Jaw operation	0.00% 0/141 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/180 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/42 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Hot flush	10.6% 15/141 • Number of events 16 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	9.4% 17/180 • Number of events 17 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	28.6% 12/42 • Number of events 12 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	44.4% 4/9 • Number of events 5 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Hypertension	12.8% 18/141 • Number of events 29 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	7.8% 14/180 • Number of events 16 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	31.0% 13/42 • Number of events 16 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	0.00% 0/9 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.
Vascular disorders Hypotension	0.71% 1/141 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	1.1% 2/180 • Number of events 2 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	2.4% 1/42 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.	11.1% 1/9 • Number of events 1 • From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm in the double-blind period. In the open-label period, the median duration of treatment was 21.6 months in participants who previously received enzalutamide and 20.9 months in participants who previously received bicalutamide. The total number of deaths (all causes) includes deaths reported after the time frame above.

Additional Information

Executive Medical Director

Astellas Pharma Global Development, Inc. (APGD)

Email: Astellas.resultsdisclosure@astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
• Publication restrictions are in place

Restriction type: OTHER