PROSPER: Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02003924
• Collaborator: Astellas Pharma Inc (Industry), Medivation LLC, a wholly owned subsidiary of Pfizer Inc. (Industry)
• Enrollment: 1,401
• Locations: 397
• Arms: 2
• Anticipated Duration (Months): 121.9
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of enzalutamide in patients with non metastatic prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Nonmetastatic Castration-Resistant Prostate Cancer; Prostate Cancer; Cancer of the Prostate	Drug: Enzalutamide; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1401 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: PROSPER: A MULTINATIONAL, PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, EFFICACY AND SAFETY STUDY OF ENZALUTAMIDE IN PATIENTS WITH NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER
• Actual Study Start Date: Oct 31, 2013
• Actual Primary Completion Date: Jun 28, 2017
• Anticipated Study Completion Date: Dec 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Placebo Sugar pill manufactured to mimic enzalutamide 40 mg capsule	Drug: Placebo; Sugar pill to mimic enzalutamide
Experimental: Enzalutamide 160 mg by mouth once daily	Drug: Enzalutamide; 160 mg by mouth once daily; Other Names: MDV3100 Xtandi

Outcome Measures

Primary Outcome Measures

1. Metastasis Free Survival (MFS) [From randomization until radiographic progression at any time, or death within 112 days of treatment discontinuation, whichever occurred first (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   MFS:time from randomization to first date of radiographic progression (RP) (by Blinded independent central radiology review [BICR]) at any time or death within 112 days of treatment discontinuation without evidence of RP.RP for bone disease:appearance of 1 or more metastatic lesions on bone scan.RP for soft tissue disease:per Response Evaluation Criteria in Solid Tumors,[RECIST 1.1])-at least a 20 percent (%) increase in the sum of diameters of target lesions,taking as reference the smallest sum on study (includes the baseline sum if smallest on study).Participants who did not have MFS event at the time of analysis data cut-off (28 June 2017) were censored at date of last assessment showing no objective evidence of RP prior to skeletal-related event or two or more consecutive missed tumor assessments. Participants who were randomized but later confirmed to have metastatic disease before randomization were censored on date of randomization. Analysis was based on Kaplan-Meier estimates.

Secondary Outcome Measures

1. Time to Prostate-Specific Antigen (PSA) Progression [From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Time to PSA progression was defined as the time from randomization to the date of first PSA value demonstrating progression, which was subsequently confirmed. For participants with PSA decline at Week 17, PSA progression was defined according to Prostate Cancer Working Group 2 (PCWG2) guidelines as the date that a 25% or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) above the nadir (or baseline for participants with no PSA decline by Week 17) was documented, which was confirmed by a second consecutive value obtained at least 3 weeks or later. Participants without confirmed PSA progression at the time of analysis were right censored at the date of last PSA assessment before the analysis data cut-off date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

2. Time to First Use of New Antineoplastic Therapy [From randomization until first use of new antineoplastic therapy(until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Time to first use of new antineoplastic therapy was defined as the time from randomization to first use of new antineoplastic for prostate cancer. Participants not starting treatment with a new antineoplastic therapy at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

3. Overall Survival [From randomization until death (up to a maximum of 68.8 months)]

   Overall survival (OS) was defined as the time (in months) from randomization to death from any cause. For participants who were alive at the time of the analysis data cutoff, OS time was censored at the last date the participant was known to be alive or analysis data cutoff date, whichever was earlier. Participants with no post baseline survival information were censored on the date of randomization. Analysis was based on Kaplan-Meier estimates.

4. Time to Pain Progression [From randomization until onset of pain progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Pain was assessed using the score from the Brief Pain Inventory-Short Form (BPI-SF) question 3: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours." Time to this event was defined as the time from randomization to onset of pain progression, where pain progression was defined as a 2-point or more increase from baseline in the question 3 score. Participants without observed pain progression at the time of analysis were right censored at the date of last pain assessment for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

5. Time to First Use of Cytotoxic Chemotherapy [From randomization up to the first use of cytotoxic chemotherapy (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Time to first use of cytotoxic chemotherapy was defined as the time from randomization to the first use of cytotoxic chemotherapy for prostate cancer. Participants not starting treatment with a cytotoxic chemotherapy for prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

6. Chemotherapy-Free Disease Specific Survival [From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Chemotherapy-free disease-specific survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer as assessed by the investigator. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died due to prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

7. Chemotherapy-Free Survival [From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   Chemotherapy-free survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died at the time of analysis were censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

8. Percentage of Participants With Prostate Specific Antigen (PSA) Response [From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

   PSA response was calculated at each visit as a decline from baseline in PSA (ng/mL) to the maximal PSA response with thresholds at 50% and 90%. Additionally, PSA response was assessed as a decline to undetectable levels, where undetectable level was defined as below the limit of quantification of the centrally assessed PSA results (the lower limit of quantification was 0.02 ng/mL). PSA response was confirmed by a second consecutive value at least 3 weeks later.

9. Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

   The FACT-P questionnaire is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess prostate-related symptoms. Each item was rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which ranged from 0 to 156 where higher scores represented better quality of life.

10. Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Mobility Domain Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the mobility questionnaire are reported.

11. Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Self-Care Domain Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the self-care questionnaire are reported.

12. Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Usual Activities Domain Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the usual activities questionnaire are reported.

13. Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Pain/Discomfort Domain Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the pain/discomfort questionnaire are reported.

14. Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Anxiety/ Depression Domain Score [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the anxiety/depression questionnaire are reported.

15. European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Status Visual Analog Score (VAS) [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

16. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 31 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 31 are reported. Question 31 was following: "Have you had to urinate frequently during the day?"

17. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 32 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 32 are reported. Question 32 was following: "Have you had to urinate frequently at night?"

18. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 33 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 33 are reported. Question 33 was following: "When you felt the urge to pass urine, did you have to hurry to get to the toilet?"

19. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 34 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 34 are reported. Question 34 was following: "Was it difficult for you to get enough sleep, because you needed to get up frequently at night to urinate?"

20. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 35 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 35 are reported. Question 35 was following: "Have you had difficulty going out of the house because you needed to be close to a toilet?"

21. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 36 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 36 are reported. Question 36 was following: "Have you had any unintentional release (leakage) of urine?"

22. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 37 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 37 are reported. Question 37 was following: "Did you have pain when you urinated?"

23. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 38 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 38 are reported. Question 38 was following: "Has wearing an incontinence aid been a problem for you?". This question was answered by only those participants who wore incontinence aid.

24. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 39 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 39 are reported. Question 39 was following: "Have your daily activities been limited by your urinary problems?"

25. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 40 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 40 are reported. Question 40 was following: "Have your daily activities been limited by your bowel problems?"

26. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 41 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 41 are reported. Question 41 was following: "Have you had any unintentional release (leakage) of stools?"

27. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 42 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 42 are reported. Question 42 was following: "Have you had blood in your stools?"

28. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 43 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 43 are reported. Question 43 was following: "Did you have a bloated feeling in your abdomen?"

29. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 44 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 44 are reported. Question 44 was following: "Did you have hot flushes?"

30. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 45 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 45 are reported. Question 45 was following: "Have you had sore or enlarged nipples or breasts?"

31. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 46 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 46 are reported. Question 46 was following: "Have you had swelling in your legs or ankles?"

32. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 47 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 47 are reported. Question 47 was following: "Has weight loss been a problem for you?"

33. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 48 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 48 are reported. Question 48 was following: "Has weight gain been a problem for you?"

34. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 49 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 49 are reported. Question 49 was following: "Have you felt less masculine as a result of your illness or treatment?"

35. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 50 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 50 are reported. Question 50 was following: "To what extent were you interested in sex?"

36. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 51 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 51 are reported. Question 51 was following: "To what extent were you sexually active (with or without intercourse)?"

37. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 52 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 52 are reported. Question 52 was following: "To what extent was sex enjoyable for you?"

38. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 53 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 53 are reported. Question 53 was following: "Did you have difficulty getting or maintaining an erection?"

39. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 54 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 54 are reported. Question 54 was following: "Did you have ejaculation problems (e.g, dry ejaculation)?"

40. Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 55 [Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177]

    The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 55 are reported. Question 55 was following: "Have you felt uncomfortable about being sexually intimate?"

41. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first). AEs included both non-serious adverse events (AEs) and SAEs.

42. Number of Participants With Treatment-Emergent Adverse Events Greater Than or Equal to Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0 [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first).Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.

43. Number of Participants With Discontinuations From Study Treatment Due to Adverse Events (AEs) [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious adverse events (AEs) and SAEs.

44. Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Hematology [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    Hematology parameters: Haemoglobin (grams per liter [g/L]); leukocytes (log 10 raised to power 9 per liter [10*9/L]); lymphocytes (log 10 raised to power 6 per liter [10*6/L]); neutrophils (log 10 raised to power 6 per liter [10*6/L]); platelets (log 10 raised to power 9 per litre [10*9/L]).

45. Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Chemistry [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    Chemistry parameters: Alanine aminotransferase (units per liter [U/L]); albumin (g/L); alkaline phosphatase (U/L); bilirubin (micromoles per liter [umol/L]); calcium (millimoles per liter [mmol/L]); creatine kinase (U/L); creatinine (umol/L); glucose, magnesium, phosphate, potassium, sodium (mmol/L).

46. Number of Participants With Clinically Significant Vital Signs [From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)]

    Vital signs included Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and heart rate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features;

• Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);

• Testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening;

• Progressive disease on androgen deprivation therapy at enrollment;

• PSA and the screening PSA assessed by the central laboratory (central PSA) should be ≥ 2 µg/L (2 ng/mL:

• PSA doubling time ≤ 10 months;

• No prior or present evidence of metastatic disease;

• Asymptomatic prostate cancer;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

• Estimated life expectancy ≥ 12 months.

Exclusion Criteria:

• Prior cytotoxic chemotherapy;

• Use of hormonal therapy or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) or use of an investigational agent within 4 weeks of randomization;

• Known or suspected brain metastasis or active leptomeningeal disease;

• History of another invasive cancer within 3 years of randomization;

• Absolute neutrophil count < 1000/μL, platelet count < 100,000/μL, or hemoglobin < 10 g/dL (6.2 mmol/L) at screening;

• Total bilirubin ≥ 1.5 times the upper limit of normal;

• Creatinine > 2 mg/dL (177 µmol/L) at screening;

• Albumin < 3.0 g/dL (30 g/L) at screening;

• History of seizure or any condition that may predispose to seizure;

• Clinically significant cardiovascular disease;

• Gastrointestinal disorder affecting absorption;

• Major surgery within 4 weeks of randomization;

• Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene;

• Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of the investigator or medical monitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urological Associates of Southern Arizona, PC	Tucson	Arizona	United States	85741
2	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
3	UCLA Clark Urology Center	Los Angeles	California	United States	90095
4	University of California, Irvine Medical Center	Orange	California	United States	92868
5	Urology Associates of San Luis Obispo, a Medical Group, Inc	San Luis Obispo	California	United States	93405
6	Urology Associates, P.C.	Englewood	Colorado	United States	80113
7	c/o Lynn Buchwalder	New Haven	Connecticut	United States	06510
8	C/O Thomas Ferencz, RPh, BCOP, Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut	United States	06510
9	Smilow Cancer Center at Yale New Haven-Hospital	New Haven	Connecticut	United States	06510
10	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
11	Yale University School of Medicine	New Haven	Connecticut	United States	06520
12	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
13	Urology of Indiana, LLC	Carmel	Indiana	United States	46032
14	First Urology, PSC	Jeffersonville	Indiana	United States	47130
15	IU Health Arnett Cancer Care	Lafayette	Indiana	United States	47904
16	Kansas City Urology Care, PA	Overland Park	Kansas	United States	66211-1231
17	GU Research Network/ Wichita Urology Group	Wichita	Kansas	United States	67226
18	Chesapeake Urology Research Associates	Baltimore	Maryland	United States	21237
19	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
20	Michigan Institute of Urology	Troy	Michigan	United States	48084
21	GU Research Network	Omaha	Nebraska	United States	68130
22	Brooklyn Urology Research Group	Brooklyn	New York	United States	11201
23	Premier Medical Group of the Hudson Valley	Newburgh	New York	United States	12550
24	Duke University Medical Center	Cary	North Carolina	United States	27518
25	Carolina Urology Partners, PLLC	Charlotte	North Carolina	United States	28277
26	Carolina Urology Partners, PLLC	Gastonia	North Carolina	United States	28054
27	Gaston Medical Associates	Gastonia	North Carolina	United States	28054
28	Carolina Urology Partners, PLLC	Huntersville	North Carolina	United States	28078
29	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina	United States	27607
30	Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
31	Oregon Urology Institute	Springfield	Oregon	United States	97477
32	Lancaster Urology	Lancaster	Pennsylvania	United States	17604
33	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
34	Vanderbilt University Medical Center, Dept. of Urologic Surgery	Nashville	Tennessee	United States	37232
35	Vanderbilt University Medical Center, The Urologic Clinic	Nashville	Tennessee	United States	37232
36	Urology San Antonio	San Antonio	Texas	United States	78229
37	Urology of Virginia, PLLC	Virginia Beach	Virginia	United States	23462
38	COIBA(Centro de Oncologia e Investigacion Buenos Aires)	Berazategui	Buenos Aires	Argentina	B1884BBF
39	Centro Medico Austral(OMI)	Caba	Buenos Aires	Argentina	C1019ABS
40	Centro de Urologia	Caba	Buenos Aires	Argentina	C1120AAT
41	Hospital Italiano de Buenos Aires	Caba	Buenos Aires	Argentina	C1199BB
42	Sanatorio Parque	Rosario	Santa FE	Argentina	CP2000
43	Instituto De Oncologia De Rosario	Rosario	Santa FE	Argentina	S200KZE
44	Clinica Universidad Reina Fabiola	Cordoba		Argentina	X5004HFP
45	Hospital Privado Centro Medico de Cordoba	Cordoba		Argentina	X5016KEH
46	Centro Oncologico Riojano Integral (CORI)	La Rioja		Argentina	F5300C0E
47	The Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
48	Border Medical Oncology Research Unit	Albury	New South Wales	Australia	2640
49	The Border Cancer Hospital Dispensary	Albury	New South Wales	Australia	2640
50	The Border Cancer Hospital	Albury	New South Wales	Australia	2640
51	Sydney cancer centre	Concord	New South Wales	Australia	2139
52	Epic pharmacy	Lismore	New South Wales	Australia	2480
53	North Coast Cancer Institute	Lismore	New South Wales	Australia	2480
54	Macquarie University Hospital	North Ryde	New South Wales	Australia	2109
55	Macquarie University	North Ryde	New South Wales	Australia	2109
56	Epic Pharmacy Port Macquarie base hospital	Port Macquarie	New South Wales	Australia	2444
57	Mid North Coast Cancer Institute	Port Macquarie	New South Wales	Australia	2444
58	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
59	The Tweed Hospital	Tweed Heads	New South Wales	Australia	2485
60	Australian Clinical Trials	Wahroonga	New South Wales	Australia	2076
61	Sydney Adventist Hospital	Wahroonga	New South Wales	Australia	2076
62	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
63	Westmead Hospital	Westmead	New South Wales	Australia	2145
64	Icon Cancer Care Wesley	Auchenflower	Queensland	Australia	4066
65	River City Pharmacy - APHS	Auchenflower	Queensland	Australia	4066
66	Icon Cancer Care Chermside	Chermside	Queensland	Australia	4032
67	Icon Cancer Care South Brisbane	South Brisbane	Queensland	Australia	4101
68	Integrated Clinical Oncology Network (ICON)	South Brisbane	Queensland	Australia	4101
69	Icon Cancer Care Southport	Southport	Queensland	Australia	4215
70	Tasman Oncology Research Pty Ltd	Southport	Queensland	Australia	4215
71	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
72	Adelaide Cancer Centre	Kurralta Park	South Australia	Australia	5037
73	Ashford Cancer Centre Research	Kurralta park	South Australia	Australia	5037
74	Cancer Care SA Pty Ltd	Kurralta Park	South Australia	Australia	5037
75	Tenpharm Pty Ltd trading as EPIC Pharmacy Tennyson	Kurralta Park	South Australia	Australia	5037
76	Box Hill Hospital (Eastern health)	Box Hill	Victoria	Australia	3128
77	Eastern Clinical Research Unit (Eastern Health)	Box Hill	Victoria	Australia	3128
78	Cabrini Hospital Brighton	Brighton	Victoria	Australia	3186
79	Monash Medical Centre	Clayton	Victoria	Australia	3168
80	Austin Health, Austin Hospital	Heidelberg	Victoria	Australia	3084
81	Cabrini Hospital Malvern	Malvern	Victoria	Australia	3144
82	Cabrini Hospital- Education and Research Precinct	Malvern	Victoria	Australia	3144
83	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
84	Sunshine Hospital	St Albans	Victoria	Australia	3021
85	Krankenhaus Barmherzige Schwestern Linz, Abteilung Radiologie	Linz	Upper Austria	Austria	4010
86	Krankenhaus Barmherzige Schwestern Linz, Abteilung Urologie	Linz	Upper Austria	Austria	4010
87	St. Vincent's Hospital, PET - CT Center	Linz	Upper Austria	Austria	4010
88	Isotopix, Ambulatorium fuer Nuklearmedizin	Vienna		Austria	1090
89	Medizinische Universitaet Wien, Universitaetsklinik fuer Innere Medizin I	Vienna		Austria	1090
90	Diagnosezentrum Meidling GesmbH	Vienna		Austria	1120
91	Algemeen Ziekenhuis Groeninge	Kortrijk	West-vlaanderen	Belgium	8500
92	Clinique Universitaire de Bruxelles Hopital Erasme	Bruxelles		Belgium	1070
93	Vzw Algemeen Ziekenhuis Maria Middelares	Gent		Belgium	9000
94	Universitaire Ziekenhuizen Leuven	Leuven		Belgium	3000
95	Centre Hospitalier Universitaire de Liege, Site du Sart-Tilman	Liege		Belgium	4000
96	Hospital Sao Rafael	Salvador	Bahia	Brazil	41253-190
97	Liga Paranaense de Combate ao cancer / Hospital Erasto Gaertner	Curitiba	Parana	Brazil	81520-060
98	Associacao Hospital de Caridade de Ijui	Ijui	RIO Grande DO SUL	Brazil	98700-000
99	Hospital da Cidade de Passo Fundo	Passo Fundo	RIO Grande DO SUL	Brazil	99010-260
100	Hospital de Clinicas de Porto Alegre	Porto Alegre	RIO Grande DO SUL	Brazil	90035-903
101	CLINIONCO - Clinica de Oncologia de Porto Alegre Ltda.	Porto Alegre	RIO Grande DO SUL	Brazil	90430-090
102	Hospital Sao Lucas da PUCRS	Porto Alegre	RIO Grande DO SUL	Brazil	90610-000
103	Instituto D'or de Pesquisa e Ensino	Rio de Janeiro	RJ	Brazil	22.281-100
104	Hospital Amaral Carvalho - Fundacao Dr. Amaral Carvalho	Jau	SAO Paulo	Brazil	17210-080
105	Fundacao Dr. Amaral Carvalho	Jau	SAO Paulo	Brazil	17210-120
106	Fundacao Dr.Amaral Carvalho	Jau	SAO Paulo	Brazil	17210-120
107	Hospital Israelita Albert Einstein	Sao Paulp	SAO Paulo	Brazil	05652-900
108	Hospital das Clinicas da Faculdade de Ciencias Medicas da UNICAMP	Campinas	SP	Brazil	13083-970
109	Centro de Estudos e Pesquisas em Hematologia e Oncologia (CEPHO)	Santo Andre	SP	Brazil	09060-650
110	IAMSPE-Inst. de Assist. ao Servidor Publico Estadual	Sao Paulo	SP	Brazil	04039-901
111	Hospital Universitario Pedro Ernesto - UERJ	Rio de Janeiro		Brazil	20551-030
112	Oncologia Rede D'Or	Rio de Janeiro		Brazil	22271-110
113	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
114	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
115	Vancouver Prostate Centre	Vancouver	British Columbia	Canada	V5Z 1M9
116	Manitoba Prostate Centre CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
117	NS Health Authority, Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
118	The Male/Female Health and Research Centre	Barrie	Ontario	Canada	L4M 7G1
119	McMaster Institute of Urology @ St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
120	Urology Associates / Urologic Medical Research	Kitchener	Ontario	Canada	N2N 2B9
121	London Regional Cancer Program - Victoria Hospital, London Health Sciences Centre(LHSC)	London	Ontario	Canada	N6A 4L6
122	Urology Reasearch - Victoria Hospital, London Health Sciences Centre(LHSC)	London	Ontario	Canada	N6A 5W9
123	SunnyBrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
124	University Health Network- Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G2M9
125	Urology South Shore Research	Greenfield Park	Quebec	Canada	J4V 2H3
126	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
127	McGill University Health Centre	Montreal	Quebec	Canada	H4A 3J1
128	CHU de Quebec	Quebec		Canada	G1R 2J6
129	Fundacion Arturo Lopez Perez	Santiago		Chile	7500836
130	Centro de Investigaciones Clinicas Vina del Mar	Santiago		Chile	7630370
131	Instituto Clinico Oncologico del Sur (ICOS)	Temuco		Chile	4810469
132	Instituto Oncologico Ltda.	Vina del Mar		Chile	2540364
133	Centro de Investigaciones Clinicas	Vina del Mar		Chile	2540488
134	Peking University First Hospital	Beijing	Beijing	China	100034
135	Beijing Cancer Hospital	Beijing	Beijing	China	100142
136	Peking University Third Hospital	Beijing	Beijing	China	100191
137	Beijing Hospital	Beijing	Beijing	China	100730
138	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
139	Chongqing Cancer Hospital	Chongqing	Chongqing	China	400030
140	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong	China	510120
141	Zhongnan Hospital of Wuhan University	Wuhan	Hubei	China	430030
142	Office of Hongqian Guo	Nanjing	Jiangsu	China	210008
143	Jiangsu Cancer Hospital	Nanjing	Jiangsu	China	210009
144	Jiangsu Province Hospital	Nanjing	Jiangsu	China	210029
145	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215004
146	Wuxi People's Hospital	Wuxi	Jiangsu	China	214023
147	Qingdao Municipal Hospital (East Hospital)	Qingdao	Shandong	China	266071
148	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
149	Huashan Hospital Fudan University	Shanghai	Shanghai	China	200040
150	Shanghai First People's Hospital	Shanghai	Shanghai	China	200080
151	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200092
152	Shanghai Changhai Hospital	Shanghai	Shanghai	China	200433
153	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi	China	710061
154	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
155	The First Affiliated Hosptial of Wenzhou Medical University	Wenzhou	Zhejiang	China	325000
156	UNIMED Medical Institute Limited	Hong Kong		China
157	The Second Hospital of Tianjin Medical University	Tianjin		China	300211
158	Rigshospitalet 7521	Copenhagen	Norrebro	Denmark	2200
159	Copenhagen Prostate Cancer Center	Copenhagen	N	Denmark	2200
160	Aarhus University Hospital	Arhus N		Denmark	8200
161	Rigshospitalet	Copenhagen		Denmark	2100
162	Frederiksberg Hospital	Frederiksberg		Denmark	2000
163	Herlev Hospital	Herlev		Denmark	2730
164	Odense University Hospital	Odense C		Denmark	5000
165	Vejle Sygehus	Vejle		Denmark	7100
166	Docrates Syopasairaala	Helsinki		Finland	00180
167	Helsingin yliopistollinen keskussairaala, Meilahden sairaala	Helsinki		Finland	00290
168	Oulun yliopistollinen sairaala	Oulu		Finland	90220
169	Satakunnan keskussairaala	Pori		Finland	28500
170	Tampereen yliopistollinen Sairaala	Tampere		Finland	33520
171	Hopitaux Universitaires de Strasbourg - Hopital Civil	STRASBOURG Cedex	Alsace	France	FR-67091
172	Centre Paul Strauss	Strasbourg	Bas-rhin	France	67000
173	Clinique Sainte Anne	Strasbourg	Bas-rhin	France	67000
174	Societe MIM, Clinique Sainte Anne	Strasbourg	Bas-rhin	France	67000
175	Institut Curie	Paris Cedex	Paris	France	75005
176	Centre Hospitalier Lyon Sud	Pierre Benite Cedex	Rhone	France	69495
177	Institut Gustave Roussy	Villejuif Cedex	VAL DE Marne	France	94805
178	Institut de Cancerologie de l'Ouest - Paul Papin	Angers Cedex 2		France	49055
179	Institut Sainte Catherine	Avignon, Cedex 9		France	84918
180	Institut Bergonie	Bordeaux Cedex		France	33076
181	Urologic Oncology Department- Institut Bergonie - Centre regional de Lutte contre le Cancer	Bordeaux Cedex		France	33076
182	Cabinet de Radiologie	Brest		France	29200
183	CHU Brest Hopital Morvan	Brest		France	29200
184	Clinique pasteur Lancroze	Brest		France	29200
185	Clinique Pasteur-Lanroze	Brest		France	29200
186	CHRU de Brest	Brest		France	29609
187	Hopital Pasteur	Colmar Cedex		France	68024
188	Hopitaux Civils de Colmar	Colmar		France	68024
189	Centre Regional de lutte Contre le Cancer Georges Francois Leclerc	Dijon		France	21000
190	Clinique Victor Hugo	Le Mans,Cedex		France	72000
191	Hopital Calude Huriez - CHU Lille	Lille		France	59037
192	Hopital Edouard Herriot - CHU Lyon	Lyon Cedex 03		France	69437
193	Centre Leon Berard	Lyon Cedex		France	69008
194	Centre de Medecine Nucleaire LUMEN	Lyon		France	69008
195	Hopital Nord	Marseille		France	13915 Cedex 20
196	ICM Val D'Aurelle	Montpellier Cedex		France	34298
197	Hopital Europeen Georges Pompidou	Paris, Cedex 15		France	75908
198	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
199	CHU Poitiers - Hopital la Miletrie	Poitiers, Cedex		France	86021
200	Institut de Cancerologie de I'Ouest - Rene Gauducheau	Saint-Herblain Cedex		France	44805
201	Clinique Pasteur - CIMOF	Toulouse Cedex 3		France	31076
202	Clinique Pasteur- Service Imagerie et Radiologie	Toulouse Cedex 3		France	31076
203	Clinique Pasteur	Toulouse Cedex 3		France	31076
204	IUCT-Oncopole	Toulouse Cedex 9		France	31059
205	Institut Claudius Regaud	Toulouse		France	31059 Cedex 9
206	Studienpraxis Urologie	Nuertingen	Baden-wuerttemberg	Germany	72622
207	Universitatsmedizin Mannheim, Medizinische Fakultat Mannheim der Universitat Heidelberg	Mannheim	Baden-wurttemberg	Germany	68167
208	MVZ Zentrum fuer Diagnostische Radiologie und Nuklearmedizin Braunschweig GmbH	Braunschweig	Niedersachsen	Germany	38102
209	Staedtisches Klinikum Braunschweig	Braunschweig	Niedersachsen	Germany	38126
210	Hannover Medical School	Hannover	Niedersachsen	Germany	30625
211	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
212	RWTH University Aachen	Aachen	Nordrhein-westfalen	Germany	52057
213	Uniklinik der RWTH Aachen	Aachen	Nordrhein-westfalen	Germany	52074
214	Clinic of Radiology	Aachen	Nordrhein-westfalen	Germany	D-52074
215	Universitaetsklinikum Carl Gustav Carus an der TU Dresden	Dresden	Saxony	Germany	01307
216	Charite, Campus Benjamin Franklin	Berlin		Germany	12200
217	Charite, Universitaetsmedizin Berlin	Berlin		Germany	12200
218	Martini-Klinik am UKE GmbH	Hamburg		Germany	20246
219	Diagnostikzentrum Esslingen	Kirchheim		Germany	73230
220	University General Hospital of Heraklion, Urology Clinic	Heraklion	Crete	Greece	71110
221	General Hospital of Athens"Korgialeneio-Benakeio EES".Urology Clinic	Athens		Greece	11526
222	General Hospital of Athens "Alexandra", Therapeutic Clinic	Athens		Greece	11528
223	University General Hospital of Larissa, Urology Department	Larissa		Greece	41110
224	University General Hospital of Patras, Oncology Department, Internal Medicine Clinic	Patra		Greece	26504
225	General Hospital" Papageorgiou",B' Univ.Urology Clinic	Thessaloniki		Greece	56429
226	Queen Mary Hospital	Hong Kong		Hong Kong
227	Tuen Mun Hospital	Hong Kong		Hong Kong
228	Prince of Wales Hospital	Shatin		Hong Kong
229	Laboratorio Medicina Nucleare-Ospedale G.B. Morgagni-Pierantoni	Forli	FC	Italy	47121
230	Farmacia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona		Italy	26100
231	Medicina Nucleare, Azienda Socio Sanitaria Territoriale di Cremona	Cremona		Italy	26100
232	Servizio di Radiologia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona		Italy	26100
233	Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona	Cremona		Italy	26100
234	U.O. di Oncologia, Ospedale Civile Degli Infermi	Faenza (RA)		Italy	48018
235	U.O. di Radiologia, Ospedale Civile degli Infermi	Faenza (RA)		Italy	48018
236	U.O. di Oncologia, Ospedale Civile Umberto I	Lugo (RA)		Italy	48022
237	U.O. di Radiologia, Ospedale Civile Umberto I	Lugo (RA)		Italy	48022
238	Laboratorio Farmaci Antiblastici	Meldola (FC)		Italy	47014
239	U.O. Oncologia Medica	Meldola (FC)		Italy	47014
240	UO Radiologia	Meldola (FC)		Italy	47014
241	Dipartimento di Radiologia, Ospedale San Raffaele	Milano		Italy	20132
242	Servizio di Farmacia, Ospedale San Raffaele	Milano		Italy	20132
243	U.O. di Medicina Nucleare e Centro PET, Ospedale San Raffaele	Milano		Italy	20132
244	U.O. di Urologia, Ospedale San Raffaele	Milano		Italy	20132
245	Farmacia Studi Clinici e Sperimentali, Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
246	S.C. di Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
247	S.C. Diagnostica Radiologica 2, Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
248	Divisione di Radiologia, Istituto Europeo di Oncologia	Milano		Italy	20141
249	Reparto Oncologia Medica Urogenitale e Cervico Facciale, Istituto Europeo di Oncologia	Milano		Italy	20141
250	Servizio Farmacia, Istituto Europeo di Oncologia	Milano		Italy	20141
251	Farmacia Interna, Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena		Italy	41124
252	Medicina Nucleare, Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena		Italy	41124
253	Radiologia I, Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena		Italy	41124
254	U.O.S.C. di Oncologia Medica, A.O.R.N. "A. Cardarelli"	Napoli		Italy	80131
255	Farmacia Ospedaliera, AOU San Luigi Gonzaga	Orbassano (TO)		Italy	10043
256	SCDU Oncologia Medica II Pad, AOU San Luigi Gonzaga	Orbassano (TO)		Italy	10043
257	SCDU Radiodiagnostica, AOU San Luigi Gonzaga	Orbassano (TO)		Italy	10043
258	SS Medicina Nucleare, AOU San Luigi Gonzaga	Orbassano (TO)		Italy	10043
259	Farmacia, Istituto Oncologico Veneto (IOV)	Padova		Italy	35128
260	IRCCS - Istituto Oncologico Veneto (IOV), UOC Oncologia Medica 1	Padova		Italy	35128
261	Medicina Nucleare, Istituto Oncologico Veneto (IOV)	Padova		Italy	35128
262	UOC Radiodiagnostica Oncologica, Istituto Oncologico Veneto (IOV)	Padova		Italy	35128
263	Ospedale Santa Maria delle Croci	Ravenna		Italy	48121
264	Servizio di Farmacia, AUSL di Ravenna	Ravenna		Italy	48121
265	Servizio di Radiologia, AUSL di Ravenna	Ravenna		Italy	48121
266	Azienda Ospedaliera S. Camillo Forlanini, UOC per il governo clinico in Oncologia Medica	Roma		Italy	00152
267	U.O. di Oncologia Medica, Ospedale Santa Chiara	Trento		Italy	38122
268	U.O. Farmacia, Ospedale Santa Chiara	Trento		Italy	38122
269	U.O. Radiologia, Ospedale Santa Chiara	Trento		Italy	38122
270	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
271	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeonnam	Korea, Republic of	58128
272	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
273	Seoul National University Hospital	Seoul		Korea, Republic of	03080
274	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
275	Asan Medical Center	Seoul		Korea, Republic of	05505
276	Gangnam Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	06273
277	Samsung Medical Center	Seoul		Korea, Republic of	06351
278	Universiti Kebangsaan Malaysia Medical Centre	Cheras	Kuala Lumpur	Malaysia	56000
279	Sarawak General Hospital	Kuching	Sarawak	Malaysia	93586
280	Subang Jaya Medical Centre Sdn. Bhd.	Subang Jaya	Selangor Darul Ehsan	Malaysia	47500
281	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia	50586
282	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
283	Maastricht University Medical Centre	Maastricht	AZ	Netherlands	5202
284	Catharina Ziekenhuis	Eindhoven	Noord-brabant	Netherlands	5623 EJ
285	Netherlands Cancer Institute	Amsterdam		Netherlands	1066 CX
286	Albert Schweitzer Ziekenhuis	Dordrecht		Netherlands	3318 AT
287	University Medical Center Groningen	Groningen		Netherlands	9700 RB
288	Radboud University Nijmegen Medical Centre	Nijmegen		Netherlands	6525 GA
289	Canterbury District Health Board	Christchurch	Canterbury	New Zealand	8140
290	Palmerston North Hospital	Palmerston North	Manawatu	New Zealand	4414
291	Cancer and Blood Research	Auckland		New Zealand	1023
292	Waikato Urology Research LTD	Hamilton		New Zealand	3214
293	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
294	UROMEDYK, Poradnia Urologiczna	Kielce		Poland	25-112
295	Malopolskie Centrum Medyczne s.c.	Krakow		Poland	30-510
296	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ	Lublin		Poland	20-718
297	Wojewodzki Szpital Specjalistyczny im. Janusza. Korczaka	Slupsk		Poland	76-200
298	Profesorskie Centrum Medyczne Optimum	Wroclaw		Poland	50-421
299	Centrum Medyczne Melita Medical	Wroclaw		Poland	50-449
300	Wro Medica	Wroclaw		Poland	51-685
301	Lexmedica	Wroclaw		Poland	53-114
302	Federal State Budgetary Institution "N.N. Blokhin Russian Cancer Research Center"	Moscow		Russian Federation	115478
303	P. Hertsen Moscow Oncology Research Institute - branch of the National Medical Research	Moscow		Russian Federation	125284
304	State Budgetary Healthcare Institution City Multifield Hospital No.2	Saint-Petersburg		Russian Federation	194354
305	SBEI HPE "First Pavlov State Medical University of St. Petersburg" of	Saint-Petersburg		Russian Federation	197002
306	SBEI HPE "First Pavlov State Medical University of St. Petersburg" of	Saint-Petersburg		Russian Federation	197022
307	Saint-Petersburg State Budgetary Healthcare Institution "Hospital for Veterans of War"	Saint-Petersburg		Russian Federation	197183
308	SBHI "Saint-Petersburg clinical scientific	Saint-Petersburg		Russian Federation	197758
309	SBEI of HPE "Bashkir State Medical University" of MoH of the RF	Ufa		Russian Federation	450073
310	Clinical Center Of Serbia, Clinic of Urology	Belgrade		Serbia	11000
311	Clinical Center "Dr Dragisa Misovic -Dedinje", Clinic of Urology	Belgrade		Serbia	11040
312	Clinical Center "Bezanijska Kosa", Department of Urology	Belgrade		Serbia	11080
313	Clinical Center Zemun	Belgrade		Serbia	11080
314	National University Hospital	Singapore		Singapore	119074
315	National Cancer Centre Singapore	Singapore		Singapore	169610
316	Fakultna nemocnica s poliklinikou F.D. Roosevelta	Banska Bystrica		Slovakia	975 17
317	Institut nuklearnej a molekularnej mediciny	Banska Bystrica		Slovakia	975 17
318	Bratislavske radiodiagnosticke centrum, a.s.	Bratislava		Slovakia	814 99
319	CUIMED, s.r.o., Urologicka ambulancia	Bratislava		Slovakia	851 05
320	Vychodoslovensky onkologicky ustav, a.s.	Kosice		Slovakia	041 91
321	Vychodoslovensky onkologicky ustav, a.s.	Kosice		Slovakia	04191
322	Institut nuklearnej a molekularnej mediciny	Kosice		Slovakia	042 53
323	Univerzitna nemocnica Martin	Martin		Slovakia	036 59
324	IZOTOPCENTRUM, s.r.o.	Nitra		Slovakia	949 01
325	Jessenius-diagnosticke centrum, a.s.	Nitra		Slovakia	949 01
326	UROEXAM spol. s r.o. urologicka ambulancia	Nitra		Slovakia	949 01
327	Alfamedis, s.r.o.	Presov		Slovakia	080 01
328	MILAB s.r.o., UROCENTRUM	Presov		Slovakia	080 01
329	Vivamed, s.r.o	Presov		Slovakia	080 01
330	UVN SNP - FN Ruzomberok, Pracovisko Nuklearnej mediciny CCSR	Ruzomberok		Slovakia	034 26
331	Fakultna nemocnica s Poliklinikou Skalica a.s	Skalica		Slovakia	909 82
332	GAMMALAB, spol. s.r.o., Oddelenie nuklearnej mediciny	Trnava		Slovakia	917 01
333	GAMMALAB, spol.s.r.o., Oddelenie nuklearnej mediciny	Trnava		Slovakia	917 01
334	KK MED s.r.o.	Zilina		Slovakia	010 01
335	Fakultna nemocnica s poliklinikou Zilina, Urologicke oddelenie	Zilina		Slovakia	012 07
336	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela	A Coruna	Spain	15706
337	Hospital Universitari Son Espases,	Palma de Mallorca	Baleares	Spain	07010
338	Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
339	ALTAHIA. Xarxa Assistencial Universitaria de Manresa	Manresa	Barcelona	Spain	08243
340	Hospital Universitario Parc Tauli	Sabadell	Barcelona	Spain	08208
341	ICO Girona-Hospital Universitari de Girona Dr. Josep Trueta	Gerona	Cataluna	Spain	17007
342	Hospital de Navarra	Pamplona	Navarra	Spain	31008
343	Complejo Hospitalario Universitario A Coruna	A Coruna		Spain	15006
344	Hospital Del Mar	Barcelona		Spain	08003
345	Cetir Centre Medic, S.L.	Barcelona		Spain	08029
346	Hospital Clinic de Barcelona	Barcelona		Spain	08036
347	Hospital Universitario de la Princesa	Madrid		Spain	28006
348	MD Anderson Cancer Center	Madrid		Spain	28033
349	Hospital Universitario 12 de octubre	Madrid		Spain	28041
350	Urologmottagningen	Goteborg		Sweden	41345
351	Diagnostiskt centrum for bild- och funktionsmedicin	Malmo		Sweden	205 02
352	Urologiska Kliniken	Malmo		Sweden	20502
353	Apoteket AB Kliniska Provningar Molnlycke	Molnlycke		Sweden	435 33
354	Karolinska Universitetssjukhuset	Solna		Sweden	17164
355	Urologmottagningen	Stockholm		Sweden	11853
356	Urologkliniken	Umea		Sweden	90185
357	Urologiska Kliniken	Örebro		Sweden	70185
358	Chang Gung Medical Fundation, Chiayi Branch(Chiayi Chang Gung Memorial Hospital)	Chiayi County		Taiwan	613
359	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
360	Kaohsiung Veterans General Hospital	Kaohsiung		Taiwan	81362
361	Chang Gung Medical Fundation,Kaohsiung (Kaohsiung Chang Gung Memorial Hospital)	Kaohsiung		Taiwan	830
362	Chang Gung Memorial Hospital, Keelung Branch (Keelung Chang Gung Memorial Hospital)	Keelung City		Taiwan	204
363	China Medical University Hospital	Taichung		Taiwan	40447
364	Taichung Veterans General Hospital	Taichung		Taiwan	40705
365	Chi Mei Medical Centre	Tainan City		Taiwan	710
366	National Taiwan University Hospital	Taipei		Taiwan	100
367	Taipei Veterans General Hospital	Taipei		Taiwan	11217
368	Chang-Gung Memorial Hospital at Linkuo	Taoyuan County		Taiwan	333
369	Maharaj Nakorn Chiang Mai Hospital	Muang	Chiang MAI	Thailand	50200
370	Songklanagarind Hospital	Hat Yai	Songkla	Thailand	90110
371	King Chulalongkorn Memorial Hospital, Chulalongkorn University	Bangkok		Thailand	10330
372	Rajavithi Hospital	Bangkok		Thailand	10400
373	Cukurova Universitesi Tip Fakultesi	Adana		Turkey	01330
374	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06100
375	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
376	Izmir Bozyaka Egitim Arastirma Hastanesi	Izmir		Turkey	35170
377	Celal Bayar Universitesi Tip Fakultesi	Manisa		Turkey	45030
378	RCI Chernivtsi Regional Clinical Hospital	Chernivtsi		Ukraine	58002
379	CI Dnipropetrovsk I.I. Mechnykov RCH, Department of Urology #2	Dnipropetrovsk		Ukraine	49005
380	CHI V.I.Shapoval RCC of Urology and Nephrology, Dep. Of Urology#4	Kharkiv		Ukraine	61037
381	Kyiv City Clinical Hospital #3, Department of Urology	Kyiv		Ukraine	02125
382	Central City Clinical Hospital, City Oncological Center	Uzhgorod		Ukraine	88000
383	CI Zaporizhzhia Regional Clinical Hospital, Dep. Of Urology,	Zaporizhzhia		Ukraine	69600
384	East and North Hertfordshire NHS Trust	Northwood	Middlesex	United Kingdom	HA6 2RN
385	Belfast Health and Social Care Trust	Belfast	Northern Ireland	United Kingdom	BT9 7AB
386	Royal Marsden NHS Foundation Trust	Sutton	Surrey	United Kingdom	SM2 5PT
387	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne	Tyne and Wear	United Kingdom	NE7 7DN
388	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B15 2TH
389	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B15 2WB
390	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8ED
391	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8HW
392	Cambridge University Hospitals NHS Foundation Trust	Cambridge		United Kingdom	CB2 0QQ
393	University College Hospitals NHS Trust	London		United Kingdom	NW1 2BU
394	Imperial College Healthcare NHS Trust	London		United Kingdom	W12 0HS
395	University College London Hospitals NHS Foundation Trust	London		United Kingdom	WC1E 6AG
396	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
397	Oxford University Hospitals NHS Trust	Oxford		United Kingdom	OX3 7LE

Sponsors and Collaborators

• Pfizer
• Astellas Pharma Inc
• Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Investigators

• Study Director: Pfizer Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Jan 26, 2018
• Statistical Analysis Plan - Nov 18, 2019

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02003924
• Other Study ID Numbers: MDV3100-14; C3431005; 2012-005665-12
• First Posted: Dec 6, 2013
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	The study was conducted at 254 sites in 32 countries.
Pre-assignment Detail	A protocol amendment was implemented to unblind all participants and those who were previously treated with placebo had an opportunity to receive open-label access to enzalutamide at the discretion of the investigator.

Arm/Group Title	Enzalutamide 160 mg	Placebo	Placebo Participants Crossover to Enzalutamide 160 mg
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.	Participants who received placebo in double-blind phase and who agreed to proceed to open-label phase, received 4 capsules of Enzalutamide 40 mg each (total dose of 160 mg per day), orally once daily (up to a maximum of 18.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Period Title: Double-blind Phase
STARTED	933	468	0
Treated	930	465	0
COMPLETED	478	87	0
NOT COMPLETED	455	381	0
Period Title: Double-blind Phase
STARTED	478	0	87
Treated	478	0	87
COMPLETED	378	0	70
NOT COMPLETED	100	0	17
Period Title: Double-blind Phase
STARTED	933	381	87
COMPLETED	566	144	80
NOT COMPLETED	367	237	7

Baseline Characteristics

Arm/Group Title	Enzalutamide 160 mg	Placebo	Total
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.	Total of all reporting groups
Overall Participants	933	468	1401
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.8 (7.83)	72.9 (7.63)	73.5 (7.77)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	933 100%	468 100%	1401 100%
Race/Ethnicity, Customized (Count of Participants)
Asian	142 15.2%	88 18.8%	230 16.4%
Black or African American	21 2.3%	10 2.1%	31 2.2%
Native Hawaiian or Other Pacific Islander	3 0.3%	2 0.4%	5 0.4%
White	671 71.9%	320 68.4%	991 70.7%
Multiple	4 0.4%	4 0.9%	8 0.6%
Other	15 1.6%	5 1.1%	20 1.4%
Missing	77 8.3%	39 8.3%	116 8.3%

Outcome Measures

1. Primary Outcome

Title	Metastasis Free Survival (MFS)
Description	MFS:time from randomization to first date of radiographic progression (RP) (by Blinded independent central radiology review [BICR]) at any time or death within 112 days of treatment discontinuation without evidence of RP.RP for bone disease:appearance of 1 or more metastatic lesions on bone scan.RP for soft tissue disease:per Response Evaluation Criteria in Solid Tumors,[RECIST 1.1])-at least a 20 percent (%) increase in the sum of diameters of target lesions,taking as reference the smallest sum on study (includes the baseline sum if smallest on study).Participants who did not have MFS event at the time of analysis data cut-off (28 June 2017) were censored at date of last assessment showing no objective evidence of RP prior to skeletal-related event or two or more consecutive missed tumor assessments. Participants who were randomized but later confirmed to have metastatic disease before randomization were censored on date of randomization. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until radiographic progression at any time, or death within 112 days of treatment discontinuation, whichever occurred first (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	36.6	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on stratified log-rank test by prostate-specific antigen (PSA) doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no). Threshold for significance at 0.05 level.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.292
	Confidence Interval	(2-Sided) 95%; 0.241 to 0.352
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

2. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression
Description	Time to PSA progression was defined as the time from randomization to the date of first PSA value demonstrating progression, which was subsequently confirmed. For participants with PSA decline at Week 17, PSA progression was defined according to Prostate Cancer Working Group 2 (PCWG2) guidelines as the date that a 25% or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) above the nadir (or baseline for participants with no PSA decline by Week 17) was documented, which was confirmed by a second consecutive value obtained at least 3 weeks or later. Participants without confirmed PSA progression at the time of analysis were right censored at the date of last PSA assessment before the analysis data cut-off date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	37.2	3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain the family-wise 2-sided type I error rate at 0.05, a parallel testing strategy between OS (with allocated type I error rate 0.03) and remaining key secondary endpoints (time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02) was performed. Testing was performed only if the primary endpoint was statistically significant.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS. Threshold for significance at 0.02 level.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.066
	Confidence Interval	(2-Sided) 95%; 0.054 to 0.081
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

3. Secondary Outcome

Title	Time to First Use of New Antineoplastic Therapy
Description	Time to first use of new antineoplastic therapy was defined as the time from randomization to first use of new antineoplastic for prostate cancer. Participants not starting treatment with a new antineoplastic therapy at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until first use of new antineoplastic therapy(until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	39.6	17.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain the family-wise 2-sided type I error rate at 0.05, a parallel testing strategy between OS (with allocated type I error rate 0.03) and remaining key secondary endpoints (time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02) was performed. Testing was performed only if the previous endpoint was statistically significant.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS. Threshold for significance at 0.02 level.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.208
	Confidence Interval	(2-Sided) 95%; 0.168 to 0.258
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time (in months) from randomization to death from any cause. For participants who were alive at the time of the analysis data cutoff, OS time was censored at the last date the participant was known to be alive or analysis data cutoff date, whichever was earlier. Participants with no post baseline survival information were censored on the date of randomization. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until death (up to a maximum of 68.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	67.0	56.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain family-wise 2-sided type I error rate at 0.05,parallel testing strategy between OS(with allocated type I error rate 0.03)and remaining key secondary endpoints(time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02)was performed.OS tested at error rate 0.05 when both time to PSA progression and time to first use of new antineoplastic therapy were significant. When either failed to show significance.OS was tested at error 0.03.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per interactive voice/web recognition system (IXRS).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.734
	Confidence Interval	(2-Sided) 95%; 0.608 to 0.885
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

5. Secondary Outcome

Title	Time to Pain Progression
Description	Pain was assessed using the score from the Brief Pain Inventory-Short Form (BPI-SF) question 3: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours." Time to this event was defined as the time from randomization to onset of pain progression, where pain progression was defined as a 2-point or more increase from baseline in the question 3 score. Participants without observed pain progression at the time of analysis were right censored at the date of last pain assessment for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until onset of pain progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	18.5	18.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6534
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.959
	Confidence Interval	(2-Sided) 95%; 0.801 to 1.149
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

6. Secondary Outcome

Title	Time to First Use of Cytotoxic Chemotherapy
Description	Time to first use of cytotoxic chemotherapy was defined as the time from randomization to the first use of cytotoxic chemotherapy for prostate cancer. Participants not starting treatment with a cytotoxic chemotherapy for prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to the first use of cytotoxic chemotherapy (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	NA	39.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.378
	Confidence Interval	(2-Sided) 95%; 0.282 to 0.507
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

7. Secondary Outcome

Title	Chemotherapy-Free Disease Specific Survival
Description	Chemotherapy-free disease-specific survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer as assessed by the investigator. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died due to prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	39.6	38.9

8. Secondary Outcome

Title	Chemotherapy-Free Survival
Description	Chemotherapy-free survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died at the time of analysis were censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Median (95% Confidence Interval) [months]	38.1	34.0

9. Secondary Outcome

Title	Percentage of Participants With Prostate Specific Antigen (PSA) Response
Description	PSA response was calculated at each visit as a decline from baseline in PSA (ng/mL) to the maximal PSA response with thresholds at 50% and 90%. Additionally, PSA response was assessed as a decline to undetectable levels, where undetectable level was defined as below the limit of quantification of the centrally assessed PSA results (the lower limit of quantification was 0.02 ng/mL). PSA response was confirmed by a second consecutive value at least 3 weeks later.
Time Frame	From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Overall number of participants analyzed' = participants with baseline and at least one post-baseline PSA assessment.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Decrease from Baseline >= 50%	76.3 8.2%	2.4 0.5%
Decrease from Baseline >= 90%	55.9 6%	0.4 0.1%
Decrease to Undetectable Level	9.6 1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease from Baseline >= 50%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	73.96
	Confidence Interval	(2-Sided) 95%; 70.91 to 77.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease from Baseline >= 90%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	55.52
	Confidence Interval	(2-Sided) 95%; 52.28 to 58.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease to Undetectable Level
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	9.65
	Confidence Interval	(2-Sided) 95%; 7.75 to 11.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score
Description	The FACT-P questionnaire is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess prostate-related symptoms. Each item was rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which ranged from 0 to 156 where higher scores represented better quality of life.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline	119.5 (17.75)	120.8 (16.73)
Change at Week 17	-4.0 (14.03)	-3.0 (13.87)
Change at Week 33	-4.6 (14.82)	-3.5 (13.74)
Change at Week 49	-3.9 (14.70)	-5.0 (15.71)
Change at Week 65	-4.0 (15.84)	-5.7 (15.04)
Change at Week 81	-4.1 (15.01)	-7.5 (16.42)
Change at Week 97	-4.9 (15.31)	-5.9 (15.80)
Change at Week 113	-5.5 (16.07)	-5.8 (13.16)
Change at Week 129	-6.3 (17.33)	-8.1 (13.99)
Change at Week 145	-5.5 (18.75)	-9.8 (15.47)
Change at Week 161	-8.9 (19.88)	-7.0 (10.95)
Change at Week 177	-4.8 (13.19)	-5.0

11. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Mobility Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the mobility questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline-No problem in walking	578 62%	298 63.7%
Baseline-slight problem in walking	183 19.6%	100 21.4%
Baseline-moderate problem in walking	100 10.7%	33 7.1%
Baseline-severe problem in walking	21 2.3%	7 1.5%
Baseline-unable to walk	2 0.2%	1 0.2%
Week 17-no problem in walking	526 56.4%	274 58.5%
Week 17-slight problem in walking	190 20.4%	88 18.8%
Week 17-moderate problem in walking	87 9.3%	50 10.7%
Week 17-severe problem in walking	32 3.4%	6 1.3%
Week 17-unable to walk	5 0.5%	1 0.2%
Week 33-no problem in walking	431 46.2%	223 47.6%
Week 33-slight problem in walking	162 17.4%	85 18.2%
Week 33-moderate problem in walking	103 11%	24 5.1%
Week 33-severe problem in walking	36 3.9%	10 2.1%
Week 33-unable to walk	6 0.6%	0 0%
Week 49-no problem in walking	362 38.8%	156 33.3%
Week 49-slight problem in walking	158 16.9%	57 12.2%
Week 49-moderate problem in walking	86 9.2%	27 5.8%
Week 49-severe problem in walking	25 2.7%	8 1.7%
Week 49-unable to walk	4 0.4%	2 0.4%
Week 65-no problem in walking	319 34.2%	121 25.9%
Week 65-slight problem in walking	109 11.7%	44 9.4%
Week 65-moderate problem in walking	75 8%	22 4.7%
Week 65-severe problem in walking	29 3.1%	6 1.3%
Week 65-unable to walk	4 0.4%	0 0%
Week 81-no problem in walking	236 25.3%	88 18.8%
Week 81-slight problem in walking	111 11.9%	39 8.3%
Week 81-moderate problem in walking	61 6.5%	15 3.2%
Week 81-severe problem in walking	26 2.8%	4 0.9%
Week 81-unable to walk	1 0.1%	2 0.4%
Week 97-no problem in walking	189 20.3%	59 12.6%
Week 97-slight problem in walking	94 10.1%	24 5.1%
Week 97-moderate problem in walking	54 5.8%	8 1.7%
Week 97-severe problem in walking	22 2.4%	4 0.9%
Week 97-unable to walk	6 0.6%	0 0%
Week 113-no problem in walking	140 15%	45 9.6%
Week 113-slight problem in walking	76 8.1%	14 3%
Week 113-moderate problem in walking	41 4.4%	11 2.4%
Week 113-severe problem in walking	14 1.5%	2 0.4%
Week 113-unable to walk	4 0.4%	1 0.2%
Week 129-no problem in walking	94 10.1%	26 5.6%
Week 129-slight problem in walking	48 5.1%	9 1.9%
Week 129-moderate problem in walking	36 3.9%	5 1.1%
Week 129-severe problem in walking	15 1.6%	1 0.2%
Week 129-unable to walk	0 0%	0 0%
Week 145-no problem in walking	56 6%	13 2.8%
Week 145-slight problem in walking	35 3.8%	5 1.1%
Week 145-moderate problem in walking	18 1.9%	2 0.4%
Week 145-severe problem in walking	7 0.8%	1 0.2%
Week 145-unable to walk	0 0%	0 0%
Week 161-no problem in walking	22 2.4%	2 0.4%
Week 161-slight problem in walking	7 0.8%	5 1.1%
Week 161-moderate problem in walking	6 0.6%	1 0.2%
Week 161-severe problem in walking	5 0.5%	0 0%
Week 161-unable to walk	0 0%	0 0%
Week 177-no problem in walking	3 0.3%	0 0%
Week 177-slight problem in walking	2 0.2%	1 0.2%
Week 177-moderate problem in walking	1 0.1%	0 0%
Week 177-severe problem in walking	0 0%	0 0%
Week 177-unable to walk	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Self-Care Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the self-care questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline:no problems washing or dressing	805 86.3%	415 88.7%
Baseline:slight problems washing or dressing	51 5.5%	23 4.9%
Baseline:moderate problems washing or dressing	22 2.4%	1 0.2%
Baseline:severe problems washing or dressing	2 0.2%	0 0%
Baseline:unable to wash or dress	4 0.4%	0 0%
Week 17:no problems washing or dressing	752 80.6%	388 82.9%
Week 17:slight problems washing or dressing	60 6.4%	26 5.6%
Week 17:moderate problems washing or dressing	21 2.3%	5 1.1%
Week 17:severe problems washing or dressing	6 0.6%	0 0%
Week 17:unable to wash or dress	1 0.1%	0 0%
Week 33:no problems washing or dressing	642 68.8%	310 66.2%
Week 33:slight problems washing or dressing	64 6.9%	20 4.3%
Week 33:moderate problems washing or dressing	21 2.3%	10 2.1%
Week 33:severe problems washing or dressing	4 0.4%	1 0.2%
Week 33:unable to wash or dress	7 0.8%	1 0.2%
Week 49:no problems washing or dressing	546 58.5%	230 49.1%
Week 49:slight problems washing or dressing	59 6.3%	9 1.9%
Week 49:moderate problems washing or dressing	23 2.5%	7 1.5%
Week 49:severe problems washing or dressing	3 0.3%	3 0.6%
Week 49:unable to wash or dress	4 0.4%	1 0.2%
Week 65:no problems washing or dressing	453 48.6%	179 38.2%
Week 65:slight problems washing or dressing	57 6.1%	11 2.4%
Week 65:moderate problems washing or dressing	14 1.5%	3 0.6%
Week 65:severe problems washing or dressing	9 1%	0 0%
Week 65:unable to wash or dress	3 0.3%	0 0%
Week 81:no problems washing or dressing	356 38.2%	132 28.2%
Week 81:slight problems washing or dressing	57 6.1%	11 2.4%
Week 81:moderate problems washing or dressing	17 1.8%	3 0.6%
Week 81:severe problems washing or dressing	3 0.3%	1 0.2%
Week 81:unable to wash or dress	2 0.2%	1 0.2%
Week 97:no problems washing or dressing	292 31.3%	85 18.2%
Week 97:slight problems washing or dressing	51 5.5%	8 1.7%
Week 97:moderate problems washing or dressing	16 1.7%	2 0.4%
Week 97:severe problems washing or dressing	1 0.1%	0 0%
Week 97:unable to wash or dress	5 0.5%	0 0%
Week 113:no problems washing or dressing	214 22.9%	60 12.8%
Week 113:slight problems washing or dressing	46 4.9%	7 1.5%
Week 113:moderate problems washing or dressing	11 1.2%	5 1.1%
Week 113:severe problems washing or dressing	0 0%	0 0%
Week 113:unable to wash or dress	4 0.4%	1 0.2%
Week 129:no problems washing or dressing	147 15.8%	35 7.5%
Week 129:slight problems washing or dressing	28 3%	5 1.1%
Week 129:moderate problems washing or dressing	16 1.7%	1 0.2%
Week 129:severe problems washing or dressing	2 0.2%	0 0%
Week 129:unable to wash or dress	0 0%	0 0%
Week 145:no problems washing or dressing	92 9.9%	15 3.2%
Week 145:slight problems washing or dressing	16 1.7%	5 1.1%
Week 145:moderate problems washing or dressing	6 0.6%	0 0%
Week 145:severe problems washing or dressing	2 0.2%	0 0%
Week 145:unable to wash or dress	0 0%	1 0.2%
Week 161:no problems washing or dressing	33 3.5%	7 1.5%
Week 161:slight problems washing or dressing	3 0.3%	0 0%
Week 161:moderate problems washing or dressing	2 0.2%	1 0.2%
Week 161:severe problems washing or dressing	1 0.1%	0 0%
Week 161:unable to wash or dress	1 0.1%	0 0%
Week 177:no problems washing or dressing	3 0.3%	1 0.2%
Week 177:slight problems washing or dressing	3 0.3%	0 0%
Week 177:moderate problems washing or dressing	0 0%	0 0%
Week 177:severe problems washing or dressing	0 0%	0 0%
Week 171:unable to wash or dress	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Usual Activities Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the usual activities questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline:no problems doing usual activities	646 69.2%	356 76.1%
Baseline:slight problems doing usual activities	167 17.9%	64 13.7%
Baseline:moderate problems	56 6%	14 3%
Baseline:severe problems	10 1.1%	5 1.1%
Baseline:unable to do usual activities	5 0.5%	0 0%
Week 17:no problems doing usual activities	571 61.2%	305 65.2%
Week 17:slight problems doing usual activities	181 19.4%	89 19%
Week 17:moderate problems	60 6.4%	24 5.1%
Week 17:severe problems	21 2.3%	0 0%
Week 17:unable to do usual activities	7 0.8%	1 0.2%
Week 33:no problems doing usual activities	474 50.8%	249 53.2%
Week 33:slight problems doing usual activities	170 18.2%	68 14.5%
Week 33:moderate problems	68 7.3%	18 3.8%
Week 33:severe problems	21 2.3%	7 1.5%
Week 33:unable to do usual activities	5 0.5%	0 0%
Week 49:no problems doing usual activities	418 44.8%	185 39.5%
Week 49:slight problems doing usual activities	137 14.7%	43 9.2%
Week 49:moderate problems	55 5.9%	14 3%
Week 49:severe problems	20 2.1%	6 1.3%
Week 49:unable to do usual activities	5 0.5%	2 0.4%
Week 65:no problems doing usual activities	338 36.2%	136 29.1%
Week 65:slight problems doing usual activities	123 13.2%	42 9%
Week 65:moderate problems	60 6.4%	11 2.4%
Week 65:severe problems	5 0.5%	4 0.9%
Week 65:unable to do usual activities	10 1.1%	0 0%
Week 81:no problems doing usual activities	267 28.6%	106 22.6%
Week 81:slight problems doing usual activities	105 11.3%	29 6.2%
Week 81:moderate problems	49 5.3%	7 1.5%
Week 81:severe problems	10 1.1%	3 0.6%
Week 81:unable to do usual activities	4 0.4%	3 0.6%
Week 97:no problems doing usual activities	224 24%	69 14.7%
Week 97:slight problems doing usual activities	90 9.6%	16 3.4%
Week 97:moderate problems	39 4.2%	8 1.7%
Week 97:severe problems	9 1%	0 0%
Week 97:unable to do usual activities	3 0.3%	2 0.4%
Week 113:no problems doing usual activities	165 17.7%	47 10%
Week 113:slight problems doing usual activities	69 7.4%	16 3.4%
Week 113:moderate problems	33 3.5%	6 1.3%
Week 113:severe problems	5 0.5%	3 0.6%
Week 113:unable to do usual activities	3 0.3%	1 0.2%
Week 129: Week :no problems doing usual activities	108 11.6%	30 6.4%
Week 129 :slight problems doing usual activities	56 6%	8 1.7%
Week 129:moderate problems	26 2.8%	3 0.6%
Week 129:severe problems	3 0.3%	0 0%
Week 129:unable to do usual activities	0 0%	0 0%
Week 145:no problems doing usual activities	67 7.2%	14 3%
Week 145:slight problems doing usual activities	35 3.8%	4 0.9%
Week 145:moderate problems	11 1.2%	2 0.4%
Week 145:severe problems	3 0.3%	1 0.2%
Week 145:unable to do usual activities	0 0%	0 0%
Week 161:no problems doing usual activities	23 2.5%	5 1.1%
Week 161:slight problems doing usual activities	9 1%	2 0.4%
Week 161:moderate problems	5 0.5%	1 0.2%
Week 161:severe problems	2 0.2%	0 0%
Week 161:unable to do usual activities	1 0.1%	0 0%
Week 177:no problems doing usual activities	3 0.3%	0 0%
Week 177:slight problems doing usual activities	2 0.2%	1 0.2%
Week 177:moderate problems	1 0.1%	0 0%
Week 177:severe problems	0 0%	0 0%
Week 177:unable to do usual activities	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Pain/Discomfort Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the pain/discomfort questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline:no pain or discomfort	546 58.5%	292 62.4%
Baseline:slight pain or discomfort	240 25.7%	117 25%
Baseline:moderate pain or discomfort	86 9.2%	25 5.3%
Baseline:severe pain or discomfort	10 1.1%	4 0.9%
Baseline:extreme pain or discomfort	2 0.2%	1 0.2%
Week 17:no pain or discomfort	464 49.7%	248 53%
Week 17:slight pain or discomfort	269 28.8%	128 27.4%
Week 17: moderate pain or discomfort	92 9.9%	41 8.8%
Week 17:severe pain or discomfort	13 1.4%	2 0.4%
Week 17:extreme pain or discomfort	2 0.2%	0 0%
Week 33:no pain or discomfort	405 43.4%	204 43.6%
Week 33:slight pain or discomfort	237 25.4%	110 23.5%
Week 33:moderate pain or discomfort	79 8.5%	21 4.5%
Week 33:severe pain or discomfort	16 1.7%	7 1.5%
Week 33:extreme pain or discomfort	1 0.1%	0 0%
Week 49:no pain or discomfort	340 36.4%	134 28.6%
Week 49:slight pain or discomfort	209 22.4%	82 17.5%
Week 49:moderate pain or discomfort	75 8%	32 6.8%
Week 49:severe pain or discomfort	10 1.1%	1 0.2%
Week 49:extreme pain or discomfort	1 0.1%	1 0.2%
Week 65:no pain or discomfort	298 31.9%	102 21.8%
Week 65:slight pain or discomfort	162 17.4%	72 15.4%
Week 65:moderate pain or discomfort	61 6.5%	15 3.2%
Week 65:severe pain or discomfort	11 1.2%	3 0.6%
Week 65:extreme pain or discomfort	4 0.4%	1 0.2%
Week 81:no pain or discomfort	231 24.8%	86 18.4%
Week 81:slight pain or discomfort	133 14.3%	45 9.6%
Week 81:moderate pain or discomfort	61 6.5%	13 2.8%
Week 81 :severe pain or discomfort	10 1.1%	2 0.4%
Week 81:extreme pain or discomfort	0 0%	2 0.4%
Week 97:no pain or discomfort	202 21.7%	58 12.4%
Week 97:slight pain or discomfort	115 12.3%	28 6%
Week 97:moderate pain or discomfort	43 4.6%	7 1.5%
Week 97:severe pain or discomfort	5 0.5%	2 0.4%
Week 97:extreme pain or discomfort	0 0%	0 0%
Week 113:no pain or discomfort	152 16.3%	47 10%
Week 113:slight pain or discomfort	80 8.6%	19 4.1%
Week 113:moderate pain or discomfort	37 4%	5 1.1%
Week 113:severe pain or discomfort	6 0.6%	2 0.4%
Week 113:extreme pain or discomfort	0 0%	0 0%
Week 129:no pain or discomfort	108 11.6%	27 5.8%
Week 129:slight pain or discomfort	55 5.9%	11 2.4%
Week 129:moderate pain or discomfort	28 3%	3 0.6%
Week 129:severe pain or discomfort	2 0.2%	0 0%
Week 129:extreme pain or discomfort	0 0%	0 0%
Week 145:no pain or discomfort	62 6.6%	12 2.6%
Week 145:slight pain or discomfort	38 4.1%	8 1.7%
Week 145:moderate pain or discomfort	15 1.6%	1 0.2%
Week 145:severe pain or discomfort	1 0.1%	0 0%
Week 145:extreme pain or discomfort	0 0%	0 0%
Week 161:no pain or discomfort	24 2.6%	2 0.4%
Week 161:slight pain or discomfort	8 0.9%	5 1.1%
Week 161:moderate pain or discomfort	5 0.5%	1 0.2%
Week 161:severe pain or discomfort	3 0.3%	0 0%
Week 161:extreme pain or discomfort	0 0%	0 0%
Week 177:no pain or discomfort	3 0.3%	0 0%
Week 177:slight pain or discomfort	1 0.1%	1 0.2%
Week 177:moderate pain or discomfort	2 0.2%	0 0%
Week 177:severe pain or discomfort	0 0%	0 0%
Week 177:extreme pain or discomfort	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Anxiety/ Depression Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the anxiety/depression questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline:not anxious or depressed	595 63.8%	310 66.2%
Baseline:slightly anxious or depressed	231 24.8%	100 21.4%
Baseline:moderately anxious or depressed	51 5.5%	24 5.1%
Baseline:severely anxious or depressed	6 0.6%	5 1.1%
Baseline:extremely anxious or depressed	1 0.1%	0 0%
Week 17:not anxious or depressed	517 55.4%	265 56.6%
Week 17:slightly anxious or depressed	251 26.9%	119 25.4%
Week 17:moderately anxious or depressed	62 6.6%	31 6.6%
Week 17:severely anxious or depressed	7 0.8%	4 0.9%
Week 17:extremely anxious or depressed	3 0.3%	0 0%
Week 33:not anxious or depressed	458 49.1%	223 47.6%
Week 33:slightly anxious or depressed	208 22.3%	89 19%
Week 33:moderately anxious or depressed	61 6.5%	23 4.9%
Week 33:severely anxious or depressed	9 1%	5 1.1%
Week 33:extremely anxious or depressed	2 0.2%	2 0.4%
Week 49:not anxious or depressed	410 43.9%	155 33.1%
Week 49:slightly anxious or depressed	172 18.4%	72 15.4%
Week 49:moderately anxious or depressed	41 4.4%	20 4.3%
Week 49:severely anxious or depressed	8 0.9%	2 0.4%
Week 49:extremely anxious or depressed	4 0.4%	1 0.2%
Week 65:not anxious or depressed	336 36%	128 27.4%
Week 65:slightly anxious or depressed	149 16%	56 12%
Week 65:moderately anxious or depressed	43 4.6%	8 1.7%
Week 65:severely anxious or depressed	8 0.9%	1 0.2%
Week 65:extremely anxious or depressed	0 0%	0 0%
Week 81:not anxious or depressed	288 30.9%	86 18.4%
Week 81:slightly anxious or depressed	106 11.4%	48 10.3%
Week 81:moderately anxious or depressed	34 3.6%	9 1.9%
Week 81:severely anxious or depressed	7 0.8%	3 0.6%
Week 81:extremely anxious or depressed	0 0%	2 0.4%
Week 97:not anxious or depressed	220 23.6%	61 13%
Week 97:slightly anxious or depressed	114 12.2%	27 5.8%
Week 97:moderately anxious or depressed	26 2.8%	6 1.3%
Week 97:severely anxious or depressed	4 0.4%	0 0%
Week 97:extremely anxious or depressed	1 0.1%	1 0.2%
Week 113:not anxious or depressed	167 17.9%	43 9.2%
Week 113:slightly anxious or depressed	87 9.3%	27 5.8%
Week 113:moderately anxious or depressed	18 1.9%	3 0.6%
Week 113:severely anxious or depressed	3 0.3%	0 0%
Week 113:extremely anxious or depressed	0 0%	0 0%
Week 129:not anxious or depressed	121 13%	28 6%
Week 129:slightly anxious or depressed	51 5.5%	10 2.1%
Week 129:moderately anxious or depressed	18 1.9%	2 0.4%
Week 129:severely anxious or depressed	2 0.2%	1 0.2%
Week 129:extremely anxious or depressed	1 0.1%	0 0%
Week 145:not anxious or depressed	73 7.8%	12 2.6%
Week 145:slightly anxious or depressed	30 3.2%	8 1.7%
Week 145:moderately anxious or depressed	10 1.1%	1 0.2%
Week 145:severely anxious or depressed	2 0.2%	0 0%
Week 145:extremely anxious or depressed	1 0.1%	0 0%
Week 161:not anxious or depressed	23 2.5%	3 0.6%
Week 161:slightly anxious or depressed	16 1.7%	4 0.9%
Week 161:moderately anxious or depressed	0 0%	1 0.2%
Week 161:severely anxious or depressed	0 0%	0 0%
Week 161:extremely anxious or depressed	1 0.1%	0 0%
Week 177:not anxious or depressed	2 0.2%	1 0.2%
Week 177:slightly anxious or depressed	2 0.2%	0 0%
Week 177:moderately anxious or depressed	2 0.2%	0 0%
Week 177:severely anxious or depressed	0 0%	0 0%
Week 177:extremely anxious or depressed	0 0%	0 0%

16. Secondary Outcome

Title	European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Status Visual Analog Score (VAS)
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline	76.2 (16.92)	77.5 (15.97)
Week 17	74.7 (17.19)	74.9 (16.79)
Week 33	74.6 (16.69)	74.0 (17.51)
Week 49	74.7 (18.02)	73.7 (18.28)
Week 65	74.5 (17.79)	73.0 (17.11)
Week 81	75.5 (17.06)	73.3 (16.82)
Week 97	74.4 (17.39)	75.2 (17.88)
Week 113	73.6 (18.05)	74.7 (15.06)
Week 129	72.8 (18.25)	77.1 (12.83)
Week 145	75.3 (17.02)	74.2 (18.13)
Week 161	74.6 (21.28)	73.8 (17.60)
Week 177	74.5 (19.31)	69.0

17. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 31
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 31 are reported. Question 31 was following: "Have you had to urinate frequently during the day?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	285 30.5%	162 34.6%
Baseline: a little	348 37.3%	160 34.2%
Baseline: quite a bit	207 22.2%	92 19.7%
Baseline: very much	44 4.7%	25 5.3%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	275 29.5%	134 28.6%
Week 17: a little	324 34.7%	168 35.9%
Week 17: quite a bit	194 20.8%	90 19.2%
Week 17: very much	46 4.9%	27 5.8%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	236 25.3%	105 22.4%
Week 33: a little	285 30.5%	145 31%
Week 33: quite a bit	176 18.9%	70 15%
Week 33: very much	40 4.3%	21 4.5%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	200 21.4%	82 17.5%
Week 49: a little	260 27.9%	92 19.7%
Week 49: quite a bit	148 15.9%	67 14.3%
Week 49: very much	27 2.9%	9 1.9%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	172 18.4%	54 11.5%
Week 65: a little	209 22.4%	79 16.9%
Week 65: quite a bit	125 13.4%	48 10.3%
Week 65: very much	30 3.2%	12 2.6%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	141 15.1%	46 9.8%
Week 81: a little	181 19.4%	60 12.8%
Week 81: quite a bit	92 9.9%	31 6.6%
Week 81: very much	20 2.1%	11 2.4%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	118 12.6%	33 7.1%
Week 97: a little	146 15.6%	40 8.5%
Week 97: quite a bit	80 8.6%	19 4.1%
Week 97: very much	21 2.3%	3 0.6%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	101 10.8%	17 3.6%
Week 113: a little	112 12%	40 8.5%
Week 113: quite a bit	46 4.9%	14 3%
Week 113: very much	16 1.7%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	70 7.5%	11 2.4%
Week 129: a little	79 8.5%	16 3.4%
Week 129: quite a bit	39 4.2%	10 2.1%
Week 129: very much	4 0.4%	4 0.9%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	42 4.5%	2 0.4%
Week 145: a little	51 5.5%	14 3%
Week 145: quite a bit	20 2.1%	4 0.9%
Week 145: very much	3 0.3%	1 0.2%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	9 1%	2 0.4%
Week 161: a little	20 2.1%	4 0.9%
Week 161: quite a bit	7 0.8%	1 0.2%
Week 161: very much	4 0.4%	1 0.2%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	0 0%	0 0%
Week 177: a little	4 0.4%	1 0.2%
Week 177: quite a bit	2 0.2%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 32
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 32 are reported. Question 32 was following: "Have you had to urinate frequently at night?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	193 20.7%	108 23.1%
Baseline: a little	423 45.3%	195 41.7%
Baseline: quite a bit	200 21.4%	103 22%
Baseline: very much	68 7.3%	33 7.1%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	194 20.8%	88 18.8%
Week 17: a little	407 43.6%	199 42.5%
Week 17: quite a bit	184 19.7%	98 20.9%
Week 17: very much	54 5.8%	34 7.3%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	173 18.5%	83 17.7%
Week 33: a little	351 37.6%	161 34.4%
Week 33: quite a bit	169 18.1%	69 14.7%
Week 33: very much	44 4.7%	28 6%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	148 15.9%	59 12.6%
Week 49: a little	313 33.5%	116 24.8%
Week 49: quite a bit	141 15.1%	59 12.6%
Week 49: very much	33 3.5%	16 3.4%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	118 12.6%	41 8.8%
Week 65: a little	266 28.5%	89 19%
Week 65: quite a bit	111 11.9%	48 10.3%
Week 65: very much	41 4.4%	15 3.2%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	91 9.8%	38 8.1%
Week 81: a little	231 24.8%	60 12.8%
Week 81: quite a bit	89 9.5%	38 8.1%
Week 81: very much	23 2.5%	12 2.6%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	88 9.4%	19 4.1%
Week 97: a little	169 18.1%	53 11.3%
Week 97: quite a bit	82 8.8%	19 4.1%
Week 97: very much	26 2.8%	4 0.9%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	67 7.2%	16 3.4%
Week 113: a little	137 14.7%	32 6.8%
Week 113: quite a bit	54 5.8%	23 4.9%
Week 113: very much	17 1.8%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	50 5.4%	9 1.9%
Week 129: a little	97 10.4%	18 3.8%
Week 129: quite a bit	37 4%	10 2.1%
Week 129: very much	8 0.9%	4 0.9%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	31 3.3%	2 0.4%
Week 145: a little	59 6.3%	14 3%
Week 145: quite a bit	24 2.6%	5 1.1%
Week 145: very much	2 0.2%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	9 1%	0 0%
Week 161: a little	23 2.5%	7 1.5%
Week 161: quite a bit	5 0.5%	0 0%
Week 161: very much	3 0.3%	1 0.2%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	2 0.2%	0 0%
Week 177: a little	2 0.2%	1 0.2%
Week 177: quite a bit	2 0.2%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 33
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 33 are reported. Question 33 was following: "When you felt the urge to pass urine, did you have to hurry to get to the toilet?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	406 43.5%	197 42.1%
Baseline: a little	266 28.5%	147 31.4%
Baseline: quite a bit	150 16.1%	70 15%
Baseline: very much	62 6.6%	25 5.3%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	350 37.5%	191 40.8%
Week 17: a little	297 31.8%	150 32.1%
Week 17: quite a bit	127 13.6%	55 11.8%
Week 17: very much	65 7%	23 4.9%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	279 29.9%	147 31.4%
Week 33: a little	278 29.8%	126 26.9%
Week 33: quite a bit	126 13.5%	48 10.3%
Week 33: very much	54 5.8%	20 4.3%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	272 29.2%	100 21.4%
Week 49: a little	222 23.8%	95 20.3%
Week 49: quite a bit	96 10.3%	38 8.1%
Week 49: very much	45 4.8%	17 3.6%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	213 22.8%	76 16.2%
Week 65: a little	213 22.8%	72 15.4%
Week 65: quite a bit	71 7.6%	31 6.6%
Week 65: very much	39 4.2%	14 3%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	181 19.4%	63 13.5%
Week 81: a little	157 16.8%	52 11.1%
Week 81: quite a bit	69 7.4%	27 5.8%
Week 81: very much	27 2.9%	6 1.3%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	146 15.6%	40 8.5%
Week 97: a little	131 14%	40 8.5%
Week 97: quite a bit	59 6.3%	12 2.6%
Week 97: very much	29 3.1%	3 0.6%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	114 12.2%	29 6.2%
Week 113: a little	106 11.4%	34 7.3%
Week 113: quite a bit	40 4.3%	9 1.9%
Week 113: very much	15 1.6%	1 0.2%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	86 9.2%	10 2.1%
Week 129: a little	72 7.7%	21 4.5%
Week 129: quite a bit	26 2.8%	6 1.3%
Week 129: very much	8 0.9%	4 0.9%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	51 5.5%	5 1.1%
Week 145: a little	39 4.2%	12 2.6%
Week 145: quite a bit	21 2.3%	4 0.9%
Week 145: very much	5 0.5%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	17 1.8%	0 0%
Week 161: a little	19 2%	5 1.1%
Week 161: quite a bit	3 0.3%	3 0.6%
Week 161: very much	1 0.1%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	2 0.2%	0 0%
Week 177: a little	1 0.1%	1 0.2%
Week 177: quite a bit	3 0.3%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

20. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 34
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 34 are reported. Question 34 was following: "Was it difficult for you to get enough sleep, because you needed to get up frequently at night to urinate?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	479 51.3%	235 50.2%
Baseline: a little	273 29.3%	146 31.2%
Baseline: quite a bit	93 10%	40 8.5%
Baseline: very much	39 4.2%	18 3.8%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	437 46.8%	214 45.7%
Week 17: a little	295 31.6%	144 30.8%
Week 17: quite a bit	75 8%	45 9.6%
Week 17: very much	32 3.4%	16 3.4%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	392 42%	180 38.5%
Week 33: a little	246 26.4%	112 23.9%
Week 33: quite a bit	75 8%	33 7.1%
Week 33: very much	24 2.6%	16 3.4%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	340 36.4%	119 25.4%
Week 49: a little	211 22.6%	94 20.1%
Week 49: quite a bit	65 7%	28 6%
Week 49: very much	19 2%	9 1.9%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	286 30.7%	92 19.7%
Week 65: a little	183 19.6%	67 14.3%
Week 65: quite a bit	47 5%	29 6.2%
Week 65: very much	20 2.1%	5 1.1%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	221 23.7%	70 15%
Week 81: a little	165 17.7%	55 11.8%
Week 81: quite a bit	37 4%	18 3.8%
Week 81: very much	11 1.2%	5 1.1%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	185 19.8%	47 10%
Week 97: a little	122 13.1%	33 7.1%
Week 97: quite a bit	43 4.6%	14 3%
Week 97: very much	15 1.6%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	135 14.5%	31 6.6%
Week 113: a little	102 10.9%	33 7.1%
Week 113: quite a bit	29 3.1%	7 1.5%
Week 113: very much	9 1%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	103 11%	13 2.8%
Week 129: a little	67 7.2%	23 4.9%
Week 129: quite a bit	19 2%	4 0.9%
Week 129: very much	3 0.3%	1 0.2%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	59 6.3%	9 1.9%
Week 145: a little	44 4.7%	10 2.1%
Week 145: quite a bit	11 1.2%	1 0.2%
Week 145: very much	2 0.2%	1 0.2%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	21 2.3%	2 0.4%
Week 161: a little	16 1.7%	5 1.1%
Week 161: quite a bit	3 0.3%	0 0%
Week 161: very much	0 0%	1 0.2%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	1 0.1%	1 0.2%
Week 177: quite a bit	2 0.2%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 35
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 35 are reported. Question 35 was following: "Have you had difficulty going out of the house because you needed to be close to a toilet?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	646 69.2%	330 70.5%
Baseline: a little	177 19%	84 17.9%
Baseline: quite a bit	45 4.8%	18 3.8%
Baseline: very much	16 1.7%	7 1.5%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	604 64.7%	295 63%
Week 17: a little	174 18.6%	100 21.4%
Week 17: quite a bit	46 4.9%	15 3.2%
Week 17: very much	15 1.6%	9 1.9%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	501 53.7%	242 51.7%
Week 33: a little	171 18.3%	74 15.8%
Week 33: quite a bit	50 5.4%	20 4.3%
Week 33: very much	15 1.6%	5 1.1%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	436 46.7%	174 37.2%
Week 49: a little	153 16.4%	53 11.3%
Week 49: quite a bit	38 4.1%	20 4.3%
Week 49: very much	8 0.9%	3 0.6%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	369 39.5%	132 28.2%
Week 65: a little	125 13.4%	50 10.7%
Week 65: quite a bit	28 3%	9 1.9%
Week 65: very much	14 1.5%	2 0.4%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	308 33%	105 22.4%
Week 81: a little	94 10.1%	35 7.5%
Week 81: quite a bit	23 2.5%	8 1.7%
Week 81: very much	9 1%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	241 25.8%	67 14.3%
Week 97: a little	91 9.8%	21 4.5%
Week 97: quite a bit	26 2.8%	6 1.3%
Week 97: very much	7 0.8%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	180 19.3%	47 10%
Week 113: a little	70 7.5%	21 4.5%
Week 113: quite a bit	18 1.9%	5 1.1%
Week 113: very much	7 0.8%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	131 14%	26 5.6%
Week 129: a little	48 5.1%	13 2.8%
Week 129: quite a bit	8 0.9%	1 0.2%
Week 129: very much	5 0.5%	1 0.2%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	74 7.9%	13 2.8%
Week 145: a little	36 3.9%	6 1.3%
Week 145: quite a bit	6 0.6%	0 0%
Week 145: very much	0 0%	2 0.4%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	24 2.6%	4 0.9%
Week 161: a little	13 1.4%	4 0.9%
Week 161: quite a bit	3 0.3%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	3 0.3%	1 0.2%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

22. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 36
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 36 are reported. Question 36 was following: "Have you had any unintentional release (leakage) of urine?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	550 58.9%	283 60.5%
Baseline: a little	273 29.3%	124 26.5%
Baseline: quite a bit	36 3.9%	20 4.3%
Baseline: very much	25 2.7%	12 2.6%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	511 54.8%	255 54.5%
Week 17: a little	264 28.3%	126 26.9%
Week 17: quite a bit	39 4.2%	27 5.8%
Week 17: very much	25 2.7%	11 2.4%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	428 45.9%	208 44.4%
Week 33: a little	246 26.4%	104 22.2%
Week 33: quite a bit	34 3.6%	19 4.1%
Week 33: very much	29 3.1%	10 2.1%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	369 39.5%	146 31.2%
Week 49: a little	209 22.4%	78 16.7%
Week 49: quite a bit	41 4.4%	22 4.7%
Week 49: very much	16 1.7%	4 0.9%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	307 32.9%	115 24.6%
Week 65: a little	170 18.2%	66 14.1%
Week 65: quite a bit	47 5%	8 1.7%
Week 65: very much	12 1.3%	4 0.9%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	248 26.6%	93 19.9%
Week 81: a little	158 16.9%	41 8.8%
Week 81: quite a bit	23 2.5%	11 2.4%
Week 81: very much	5 0.5%	3 0.6%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	195 20.9%	55 11.8%
Week 97: a little	134 14.4%	33 7.1%
Week 97: quite a bit	25 2.7%	7 1.5%
Week 97: very much	11 1.2%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	160 17.1%	42 9%
Week 113: a little	91 9.8%	28 6%
Week 113: quite a bit	17 1.8%	3 0.6%
Week 113: very much	7 0.8%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	109 11.7%	22 4.7%
Week 129: a little	68 7.3%	13 2.8%
Week 129: quite a bit	13 1.4%	5 1.1%
Week 129: very much	2 0.2%	1 0.2%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	58 6.2%	9 1.9%
Week 145: a little	45 4.8%	11 2.4%
Week 145: quite a bit	10 1.1%	0 0%
Week 145: very much	3 0.3%	1 0.2%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	18 1.9%	3 0.6%
Week 161: a little	21 2.3%	4 0.9%
Week 161: quite a bit	0 0%	1 0.2%
Week 161: very much	1 0.1%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	1 0.1%	0 0%
Week 177: a little	3 0.3%	1 0.2%
Week 177: quite a bit	1 0.1%	0 0%
Week 177: very much	1 0.1%	0 0%
Week 177: not answered	0 0%	0 0%

23. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 37
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 37 are reported. Question 37 was following: "Did you have pain when you urinated?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	775 83.1%	380 81.2%
Baseline: a little	92 9.9%	47 10%
Baseline: quite a bit	10 1.1%	8 1.7%
Baseline: very much	7 0.8%	4 0.9%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	762 81.7%	351 75%
Week 17: a little	65 7%	58 12.4%
Week 17: quite a bit	12 1.3%	8 1.7%
Week 17: very much	0 0%	2 0.4%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	662 71%	291 62.2%
Week 33: a little	63 6.8%	39 8.3%
Week 33: quite a bit	11 1.2%	8 1.7%
Week 33: very much	1 0.1%	3 0.6%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	577 61.8%	209 44.7%
Week 49: a little	49 5.3%	34 7.3%
Week 49: quite a bit	6 0.6%	3 0.6%
Week 49: very much	3 0.3%	4 0.9%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	492 52.7%	161 34.4%
Week 65: a little	32 3.4%	29 6.2%
Week 65: quite a bit	9 1%	2 0.4%
Week 65: very much	3 0.3%	1 0.2%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	389 41.7%	119 25.4%
Week 81: a little	40 4.3%	27 5.8%
Week 81: quite a bit	4 0.4%	2 0.4%
Week 81: very much	1 0.1%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	332 35.6%	84 17.9%
Week 97: a little	28 3%	11 2.4%
Week 97: quite a bit	4 0.4%	0 0%
Week 97: very much	1 0.1%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	247 26.5%	57 12.2%
Week 113: a little	26 2.8%	13 2.8%
Week 113: quite a bit	1 0.1%	3 0.6%
Week 113: very much	1 0.1%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	173 18.5%	34 7.3%
Week 129: a little	16 1.7%	7 1.5%
Week 129: quite a bit	1 0.1%	0 0%
Week 129: very much	2 0.2%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	102 10.9%	15 3.2%
Week 145: a little	14 1.5%	6 1.3%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	36 3.9%	6 1.3%
Week 161: a little	3 0.3%	1 0.2%
Week 161: quite a bit	1 0.1%	1 0.2%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	6 0.6%	0 0%
Week 177: a little	0 0%	1 0.2%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

24. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 38
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 38 are reported. Question 38 was following: "Has wearing an incontinence aid been a problem for you?". This question was answered by only those participants who wore incontinence aid.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	83 8.9%	37 7.9%
Baseline: a little	40 4.3%	19 4.1%
Baseline: quite a bit	15 1.6%	3 0.6%
Baseline: very much	6 0.6%	8 1.7%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	77 8.3%	34 7.3%
Week 17: a little	48 5.1%	21 4.5%
Week 17: quite a bit	15 1.6%	7 1.5%
Week 17: very much	6 0.6%	6 1.3%
Week 17: not answered	693 74.3%	351 75%
Week 33: not at all	76 8.1%	30 6.4%
Week 33: a little	47 5%	28 6%
Week 33: quite a bit	16 1.7%	4 0.9%
Week 33: very much	5 0.5%	4 0.9%
Week 33: not answered	593 63.6%	275 58.8%
Week 49: not at all	73 7.8%	18 3.8%
Week 49: a little	43 4.6%	16 3.4%
Week 49: quite a bit	12 1.3%	9 1.9%
Week 49: very much	4 0.4%	2 0.4%
Week 49: not answered	503 53.9%	205 43.8%
Week 65: not at all	63 6.8%	12 2.6%
Week 65: a little	40 4.3%	17 3.6%
Week 65: quite a bit	9 1%	5 1.1%
Week 65: very much	3 0.3%	1 0.2%
Week 65: not answered	421 45.1%	158 33.8%
Week 81: not at all	52 5.6%	15 3.2%
Week 81: a little	33 3.5%	9 1.9%
Week 81: quite a bit	10 1.1%	1 0.2%
Week 81: very much	3 0.3%	3 0.6%
Week 81: not answered	336 36%	120 25.6%
Week 97: not at all	50 5.4%	8 1.7%
Week 97: a little	28 3%	8 1.7%
Week 97: quite a bit	7 0.8%	2 0.4%
Week 97: very much	3 0.3%	0 0%
Week 97: not answered	277 29.7%	77 16.5%
Week 113: not at all	31 3.3%	12 2.6%
Week 113: a little	18 1.9%	7 1.5%
Week 113: quite a bit	8 0.9%	2 0.4%
Week 113: very much	2 0.2%	0 0%
Week 113: not answered	216 23.2%	52 11.1%
Week 129: not at all	27 2.9%	5 1.1%
Week 129: a little	18 1.9%	5 1.1%
Week 129: quite a bit	2 0.2%	1 0.2%
Week 129: very much	0 0%	0 0%
Week 129: not answered	145 15.5%	30 6.4%
Week 145: not at all	16 1.7%	2 0.4%
Week 145: a little	10 1.1%	4 0.9%
Week 145: quite a bit	5 0.5%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	85 9.1%	15 3.2%
Week 161: not at all	10 1.1%	1 0.2%
Week 161: a little	3 0.3%	2 0.4%
Week 161: quite a bit	1 0.1%	1 0.2%
Week 161: very much	0 0%	0 0%
Week 161: not answered	26 2.8%	4 0.9%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	1 0.1%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	2 0.2%	1 0.2%

25. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 39
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 39 are reported. Question 39 was following: "Have your daily activities been limited by your urinary problems?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	666 71.4%	338 72.2%
Baseline: a little	173 18.5%	80 17.1%
Baseline: quite a bit	35 3.8%	11 2.4%
Baseline: very much	10 1.1%	10 2.1%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	632 67.7%	305 65.2%
Week 17: a little	160 17.1%	99 21.2%
Week 17: quite a bit	36 3.9%	6 1.3%
Week 17: very much	11 1.2%	9 1.9%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	523 56.1%	242 51.7%
Week 33: a little	172 18.4%	79 16.9%
Week 33: quite a bit	31 3.3%	14 3%
Week 33: very much	11 1.2%	6 1.3%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	444 47.6%	173 37%
Week 49: a little	152 16.3%	58 12.4%
Week 49: quite a bit	31 3.3%	18 3.8%
Week 49: very much	8 0.9%	1 0.2%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	382 40.9%	128 27.4%
Week 65: a little	124 13.3%	51 10.9%
Week 65: quite a bit	20 2.1%	12 2.6%
Week 65: very much	10 1.1%	2 0.4%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	310 33.2%	103 22%
Week 81: a little	98 10.5%	35 7.5%
Week 81: quite a bit	21 2.3%	8 1.7%
Week 81: very much	5 0.5%	2 0.4%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	242 25.9%	72 15.4%
Week 97: a little	100 10.7%	18 3.8%
Week 97: quite a bit	18 1.9%	4 0.9%
Week 97: very much	5 0.5%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	188 20.2%	54 11.5%
Week 113: a little	71 7.6%	14 3%
Week 113: quite a bit	13 1.4%	3 0.6%
Week 113: very much	3 0.3%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	127 13.6%	25 5.3%
Week 129: a little	55 5.9%	14 3%
Week 129: quite a bit	7 0.8%	1 0.2%
Week 129: very much	3 0.3%	1 0.2%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	77 8.3%	11 2.4%
Week 145: a little	34 3.6%	9 1.9%
Week 145: quite a bit	4 0.4%	1 0.2%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	27 2.9%	2 0.4%
Week 161: a little	10 1.1%	6 1.3%
Week 161: quite a bit	3 0.3%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	3 0.3%	1 0.2%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

26. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 40
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 40 are reported. Question 40 was following: "Have your daily activities been limited by your bowel problems?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	758 81.2%	393 84%
Baseline: a little	112 12%	40 8.5%
Baseline: quite a bit	9 1%	4 0.9%
Baseline: very much	5 0.5%	2 0.4%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	707 75.8%	352 75.2%
Week 17: a little	107 11.5%	57 12.2%
Week 17: quite a bit	19 2%	6 1.3%
Week 17: very much	6 0.6%	4 0.9%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	621 66.6%	292 62.4%
Week 33: a little	98 10.5%	40 8.5%
Week 33: quite a bit	14 1.5%	8 1.7%
Week 33: very much	4 0.4%	1 0.2%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	525 56.3%	211 45.1%
Week 49: a little	88 9.4%	29 6.2%
Week 49: quite a bit	20 2.1%	7 1.5%
Week 49: very much	2 0.2%	3 0.6%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	441 47.3%	165 35.3%
Week 65: a little	78 8.4%	24 5.1%
Week 65: quite a bit	11 1.2%	3 0.6%
Week 65: very much	6 0.6%	1 0.2%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	360 38.6%	121 25.9%
Week 81: a little	56 6%	23 4.9%
Week 81: quite a bit	17 1.8%	3 0.6%
Week 81: very much	1 0.1%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	289 31%	84 17.9%
Week 97: a little	58 6.2%	11 2.4%
Week 97: quite a bit	17 1.8%	0 0%
Week 97: very much	1 0.1%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	219 23.5%	62 13.2%
Week 113: a little	46 4.9%	11 2.4%
Week 113: quite a bit	8 0.9%	0 0%
Week 113: very much	2 0.2%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	153 16.4%	36 7.7%
Week 129: a little	33 3.5%	5 1.1%
Week 129: quite a bit	5 0.5%	0 0%
Week 129: very much	1 0.1%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	93 10%	17 3.6%
Week 145: a little	19 2%	4 0.9%
Week 145: quite a bit	4 0.4%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	29 3.1%	8 1.7%
Week 161: a little	9 1%	0 0%
Week 161: quite a bit	2 0.2%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	4 0.4%	1 0.2%
Week 177: a little	2 0.2%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

27. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 41
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 41 are reported. Question 41 was following: "Have you had any unintentional release (leakage) of stools?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	794 85.1%	404 86.3%
Baseline: a little	78 8.4%	32 6.8%
Baseline: quite a bit	11 1.2%	2 0.4%
Baseline: very much	1 0.1%	1 0.2%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	751 80.5%	372 79.5%
Week 17: a little	79 8.5%	43 9.2%
Week 17: quite a bit	8 0.9%	3 0.6%
Week 17: very much	1 0.1%	1 0.2%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	638 68.4%	307 65.6%
Week 33: a little	92 9.9%	32 6.8%
Week 33: quite a bit	4 0.4%	1 0.2%
Week 33: very much	3 0.3%	1 0.2%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	554 59.4%	221 47.2%
Week 49: a little	73 7.8%	25 5.3%
Week 49: quite a bit	5 0.5%	4 0.9%
Week 49: very much	3 0.3%	0 0%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	467 50.1%	175 37.4%
Week 65: a little	57 6.1%	16 3.4%
Week 65: quite a bit	9 1%	1 0.2%
Week 65: very much	3 0.3%	1 0.2%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	380 40.7%	136 29.1%
Week 81: a little	51 5.5%	12 2.6%
Week 81: quite a bit	2 0.2%	0 0%
Week 81: very much	1 0.1%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	315 33.8%	86 18.4%
Week 97: a little	47 5%	9 1.9%
Week 97: quite a bit	3 0.3%	0 0%
Week 97: very much	0 0%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	233 25%	66 14.1%
Week 113: a little	40 4.3%	7 1.5%
Week 113: quite a bit	2 0.2%	0 0%
Week 113: very much	0 0%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	167 17.9%	39 8.3%
Week 129: a little	25 2.7%	2 0.4%
Week 129: quite a bit	0 0%	0 0%
Week 129: very much	0 0%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	93 10%	20 4.3%
Week 145: a little	22 2.4%	1 0.2%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	30 3.2%	8 1.7%
Week 161: a little	9 1%	0 0%
Week 161: quite a bit	0 0%	0 0%
Week 161: very much	1 0.1%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	4 0.4%	1 0.2%
Week 177: a little	2 0.2%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

28. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 42
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 42 are reported. Question 42 was following: "Have you had blood in your stools?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	836 89.6%	422 90.2%
Baseline: a little	48 5.1%	17 3.6%
Baseline: quite a bit	0 0%	0 0%
Baseline: very much	0 0%	0 0%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	801 85.9%	399 85.3%
Week 17: a little	36 3.9%	18 3.8%
Week 17: quite a bit	2 0.2%	2 0.4%
Week 17: very much	0 0%	0 0%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	707 75.8%	330 70.5%
Week 33: a little	29 3.1%	11 2.4%
Week 33: quite a bit	1 0.1%	0 0%
Week 33: very much	0 0%	0 0%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	608 65.2%	245 52.4%
Week 49: a little	27 2.9%	5 1.1%
Week 49: quite a bit	0 0%	0 0%
Week 49: very much	0 0%	0 0%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	514 55.1%	180 38.5%
Week 65: a little	19 2%	13 2.8%
Week 65: quite a bit	3 0.3%	0 0%
Week 65: very much	0 0%	0 0%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	420 45%	143 30.6%
Week 81: a little	14 1.5%	4 0.9%
Week 81: quite a bit	0 0%	1 0.2%
Week 81: very much	0 0%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	357 38.3%	93 19.9%
Week 97: a little	8 0.9%	2 0.4%
Week 97: quite a bit	0 0%	0 0%
Week 97: very much	0 0%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	262 28.1%	72 15.4%
Week 113: a little	13 1.4%	1 0.2%
Week 113: quite a bit	0 0%	0 0%
Week 113: very much	0 0%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	186 19.9%	41 8.8%
Week 129: a little	5 0.5%	0 0%
Week 129: quite a bit	1 0.1%	0 0%
Week 129: very much	0 0%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	114 12.2%	21 4.5%
Week 145: a little	2 0.2%	0 0%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	38 4.1%	8 1.7%
Week 161: a little	2 0.2%	0 0%
Week 161: quite a bit	0 0%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	6 0.6%	1 0.2%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

29. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 43
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 43 are reported. Question 43 was following: "Did you have a bloated feeling in your abdomen?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	667 71.5%	320 68.4%
Baseline: a little	190 20.4%	103 22%
Baseline: quite a bit	22 2.4%	16 3.4%
Baseline: very much	5 0.5%	0 0%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	601 64.4%	283 60.5%
Week 17: a little	199 21.3%	121 25.9%
Week 17: quite a bit	31 3.3%	13 2.8%
Week 17: very much	8 0.9%	2 0.4%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	526 56.4%	235 50.2%
Week 33: a little	183 19.6%	95 20.3%
Week 33: quite a bit	22 2.4%	8 1.7%
Week 33: very much	6 0.6%	3 0.6%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	449 48.1%	174 37.2%
Week 49: a little	163 17.5%	63 13.5%
Week 49: quite a bit	20 2.1%	11 2.4%
Week 49: very much	3 0.3%	2 0.4%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	381 40.8%	135 28.8%
Week 65: a little	132 14.1%	51 10.9%
Week 65: quite a bit	19 2%	7 1.5%
Week 65: very much	4 0.4%	0 0%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	304 32.6%	103 22%
Week 81: a little	110 11.8%	44 9.4%
Week 81: quite a bit	18 1.9%	1 0.2%
Week 81: very much	2 0.2%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	258 27.7%	72 15.4%
Week 97: a little	87 9.3%	23 4.9%
Week 97: quite a bit	19 2%	0 0%
Week 97: very much	1 0.1%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	199 21.3%	55 11.8%
Week 113: a little	66 7.1%	18 3.8%
Week 113: quite a bit	9 1%	0 0%
Week 113: very much	1 0.1%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	139 14.9%	25 5.3%
Week 129: a little	43 4.6%	16 3.4%
Week 129: quite a bit	8 0.9%	0 0%
Week 129: very much	2 0.2%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	87 9.3%	13 2.8%
Week 145: a little	24 2.6%	8 1.7%
Week 145: quite a bit	4 0.4%	0 0%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	33 3.5%	6 1.3%
Week 161: a little	7 0.8%	2 0.4%
Week 161: quite a bit	0 0%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	4 0.4%	0 0%
Week 177: a little	2 0.2%	1 0.2%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

30. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 44
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 44 are reported. Question 44 was following: "Did you have hot flushes?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	374 40.1%	177 37.8%
Baseline: a little	314 33.7%	166 35.5%
Baseline: quite a bit	151 16.2%	68 14.5%
Baseline: very much	45 4.8%	28 6%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	265 28.4%	182 38.9%
Week 17: a little	311 33.3%	153 32.7%
Week 17: quite a bit	189 20.3%	62 13.2%
Week 17: very much	74 7.9%	22 4.7%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	253 27.1%	144 30.8%
Week 33: a little	268 28.7%	116 24.8%
Week 33: quite a bit	155 16.6%	60 12.8%
Week 33: very much	61 6.5%	21 4.5%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	227 24.3%	112 23.9%
Week 49: a little	235 25.2%	94 20.1%
Week 49: quite a bit	130 13.9%	30 6.4%
Week 49: very much	43 4.6%	14 3%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	203 21.8%	79 16.9%
Week 65: a little	194 20.8%	77 16.5%
Week 65: quite a bit	104 11.1%	30 6.4%
Week 65: very much	35 3.8%	7 1.5%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	175 18.8%	69 14.7%
Week 81: a little	157 16.8%	58 12.4%
Week 81: quite a bit	75 8%	16 3.4%
Week 81: very much	27 2.9%	5 1.1%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	155 16.6%	48 10.3%
Week 97: a little	126 13.5%	34 7.3%
Week 97: quite a bit	57 6.1%	12 2.6%
Week 97: very much	27 2.9%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	114 12.2%	33 7.1%
Week 113: a little	102 10.9%	24 5.1%
Week 113: quite a bit	44 4.7%	14 3%
Week 113: very much	15 1.6%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	84 9%	22 4.7%
Week 129: a little	74 7.9%	16 3.4%
Week 129: quite a bit	23 2.5%	3 0.6%
Week 129: very much	11 1.2%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	45 4.8%	10 2.1%
Week 145: a little	46 4.9%	10 2.1%
Week 145: quite a bit	18 1.9%	0 0%
Week 145: very much	7 0.8%	1 0.2%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	18 1.9%	3 0.6%
Week 161: a little	14 1.5%	3 0.6%
Week 161: quite a bit	5 0.5%	2 0.4%
Week 161: very much	3 0.3%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	1 0.1%	1 0.2%
Week 177: very much	2 0.2%	0 0%
Week 177: not answered	0 0%	0 0%

31. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 45
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 45 are reported. Question 45 was following: "Have you had sore or enlarged nipples or breasts?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	688 73.7%	333 71.2%
Baseline: a little	146 15.6%	80 17.1%
Baseline: quite a bit	38 4.1%	24 5.1%
Baseline: very much	12 1.3%	2 0.4%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	626 67.1%	315 67.3%
Week 17: a little	160 17.1%	80 17.1%
Week 17: quite a bit	39 4.2%	18 3.8%
Week 17: very much	14 1.5%	6 1.3%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	526 56.4%	260 55.6%
Week 33: a little	164 17.6%	62 13.2%
Week 33: quite a bit	34 3.6%	15 3.2%
Week 33: very much	13 1.4%	4 0.9%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	444 47.6%	188 40.2%
Week 49: a little	138 14.8%	52 11.1%
Week 49: quite a bit	41 4.4%	5 1.1%
Week 49: very much	12 1.3%	5 1.1%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	371 39.8%	149 31.8%
Week 65: a little	119 12.8%	37 7.9%
Week 65: quite a bit	31 3.3%	7 1.5%
Week 65: very much	15 1.6%	0 0%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	306 32.8%	115 24.6%
Week 81: a little	84 9%	26 5.6%
Week 81: quite a bit	34 3.6%	6 1.3%
Week 81: very much	10 1.1%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	239 25.6%	80 17.1%
Week 97: a little	92 9.9%	13 2.8%
Week 97: quite a bit	30 3.2%	1 0.2%
Week 97: very much	4 0.4%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	190 20.4%	55 11.8%
Week 113: a little	62 6.6%	12 2.6%
Week 113: quite a bit	19 2%	5 1.1%
Week 113: very much	4 0.4%	1 0.2%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	128 13.7%	30 6.4%
Week 129: a little	51 5.5%	8 1.7%
Week 129: quite a bit	9 1%	3 0.6%
Week 129: very much	4 0.4%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	78 8.4%	17 3.6%
Week 145: a little	29 3.1%	3 0.6%
Week 145: quite a bit	7 0.8%	1 0.2%
Week 145: very much	2 0.2%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	26 2.8%	4 0.9%
Week 161: a little	11 1.2%	3 0.6%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	2 0.2%	1 0.2%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	2 0.2%	0 0%
Week 177: a little	2 0.2%	1 0.2%
Week 177: quite a bit	2 0.2%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

32. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 46
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 46 are reported. Question 46 was following: "Have you had swelling in your legs or ankles?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	663 71.1%	323 69%
Baseline: a little	189 20.3%	89 19%
Baseline: quite a bit	22 2.4%	22 4.7%
Baseline: very much	10 1.1%	5 1.1%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	625 67%	284 60.7%
Week 17: a little	179 19.2%	112 23.9%
Week 17: quite a bit	30 3.2%	21 4.5%
Week 17: very much	5 0.5%	2 0.4%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	530 56.8%	243 51.9%
Week 33: a little	159 17%	76 16.2%
Week 33: quite a bit	41 4.4%	20 4.3%
Week 33: very much	7 0.8%	2 0.4%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	453 48.6%	176 37.6%
Week 49: a little	155 16.6%	58 12.4%
Week 49: quite a bit	23 2.5%	15 3.2%
Week 49: very much	4 0.4%	1 0.2%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	378 40.5%	135 28.8%
Week 65: a little	127 13.6%	48 10.3%
Week 65: quite a bit	27 2.9%	10 2.1%
Week 65: very much	4 0.4%	0 0%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	301 32.3%	104 22.2%
Week 81: a little	102 10.9%	36 7.7%
Week 81: quite a bit	27 2.9%	7 1.5%
Week 81: very much	4 0.4%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	259 27.8%	69 14.7%
Week 97: a little	79 8.5%	20 4.3%
Week 97: quite a bit	19 2%	5 1.1%
Week 97: very much	8 0.9%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	191 20.5%	40 8.5%
Week 113: a little	65 7%	27 5.8%
Week 113: quite a bit	16 1.7%	6 1.3%
Week 113: very much	3 0.3%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	134 14.4%	27 5.8%
Week 129: a little	48 5.1%	14 3%
Week 129: quite a bit	8 0.9%	0 0%
Week 129: very much	2 0.2%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	76 8.1%	15 3.2%
Week 145: a little	34 3.6%	5 1.1%
Week 145: quite a bit	5 0.5%	1 0.2%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	31 3.3%	6 1.3%
Week 161: a little	8 0.9%	2 0.4%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	3 0.3%	0 0%
Week 177: quite a bit	0 0%	1 0.2%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

33. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 47
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 47 are reported. Question 47 was following: "Has weight loss been a problem for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	820 87.9%	399 85.3%
Baseline: a little	48 5.1%	25 5.3%
Baseline: quite a bit	10 1.1%	10 2.1%
Baseline: very much	6 0.6%	5 1.1%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	733 78.6%	375 80.1%
Week 17: a little	81 8.7%	28 6%
Week 17: quite a bit	15 1.6%	13 2.8%
Week 17: very much	10 1.1%	3 0.6%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	643 68.9%	296 63.2%
Week 33: a little	72 7.7%	35 7.5%
Week 33: quite a bit	13 1.4%	5 1.1%
Week 33: very much	9 1%	5 1.1%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	553 59.3%	215 45.9%
Week 49: a little	61 6.5%	29 6.2%
Week 49: quite a bit	15 1.6%	3 0.6%
Week 49: very much	6 0.6%	3 0.6%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	479 51.3%	168 35.9%
Week 65: a little	39 4.2%	20 4.3%
Week 65: quite a bit	11 1.2%	4 0.9%
Week 65: very much	7 0.8%	1 0.2%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	371 39.8%	136 29.1%
Week 81: a little	46 4.9%	10 2.1%
Week 81: quite a bit	14 1.5%	1 0.2%
Week 81: very much	3 0.3%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	314 33.7%	84 17.9%
Week 97: a little	36 3.9%	10 2.1%
Week 97: quite a bit	10 1.1%	0 0%
Week 97: very much	5 0.5%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	235 25.2%	62 13.2%
Week 113: a little	27 2.9%	8 1.7%
Week 113: quite a bit	9 1%	1 0.2%
Week 113: very much	4 0.4%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	169 18.1%	37 7.9%
Week 129: a little	17 1.8%	4 0.9%
Week 129: quite a bit	5 0.5%	0 0%
Week 129: very much	1 0.1%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	95 10.2%	20 4.3%
Week 145: a little	17 1.8%	1 0.2%
Week 145: quite a bit	4 0.4%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	34 3.6%	8 1.7%
Week 161: a little	5 0.5%	0 0%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	5 0.5%	1 0.2%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	1 0.1%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

34. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 48
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 48 are reported. Question 48 was following: "Has weight gain been a problem for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	677 72.6%	315 67.3%
Baseline: a little	153 16.4%	95 20.3%
Baseline: quite a bit	40 4.3%	16 3.4%
Baseline: very much	14 1.5%	13 2.8%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	674 72.2%	316 67.5%
Week 17: a little	118 12.6%	74 15.8%
Week 17: quite a bit	30 3.2%	19 4.1%
Week 17: very much	17 1.8%	10 2.1%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	570 61.1%	259 55.3%
Week 33: a little	133 14.3%	59 12.6%
Week 33: quite a bit	21 2.3%	18 3.8%
Week 33: very much	13 1.4%	5 1.1%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	479 51.3%	193 41.2%
Week 49: a little	125 13.4%	44 9.4%
Week 49: quite a bit	18 1.9%	10 2.1%
Week 49: very much	13 1.4%	3 0.6%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	410 43.9%	155 33.1%
Week 65: a little	92 9.9%	27 5.8%
Week 65: quite a bit	26 2.8%	9 1.9%
Week 65: very much	8 0.9%	2 0.4%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	327 35%	115 24.6%
Week 81: a little	71 7.6%	27 5.8%
Week 81: quite a bit	28 3%	5 1.1%
Week 81: very much	8 0.9%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	267 28.6%	76 16.2%
Week 97: a little	70 7.5%	16 3.4%
Week 97: quite a bit	24 2.6%	2 0.4%
Week 97: very much	4 0.4%	1 0.2%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	200 21.4%	60 12.8%
Week 113: a little	56 6%	10 2.1%
Week 113: quite a bit	10 1.1%	3 0.6%
Week 113: very much	9 1%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	156 16.7%	32 6.8%
Week 129: a little	27 2.9%	8 1.7%
Week 129: quite a bit	5 0.5%	1 0.2%
Week 129: very much	4 0.4%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	89 9.5%	16 3.4%
Week 145: a little	18 1.9%	5 1.1%
Week 145: quite a bit	7 0.8%	0 0%
Week 145: very much	2 0.2%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	31 3.3%	6 1.3%
Week 161: a little	6 0.6%	2 0.4%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	2 0.2%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	2 0.2%	0 0%
Week 177: a little	3 0.3%	1 0.2%
Week 177: quite a bit	1 0.1%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

35. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 49
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 49 are reported. Question 49 was following: "Have you felt less masculine as a result of your illness or treatment?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	435 46.6%	214 45.7%
Baseline: a little	234 25.1%	131 28%
Baseline: quite a bit	138 14.8%	59 12.6%
Baseline: very much	77 8.3%	35 7.5%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	400 42.9%	210 44.9%
Week 17: a little	244 26.2%	115 24.6%
Week 17: quite a bit	109 11.7%	57 12.2%
Week 17: very much	86 9.2%	37 7.9%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	345 37%	167 35.7%
Week 33: a little	207 22.2%	107 22.9%
Week 33: quite a bit	109 11.7%	38 8.1%
Week 33: very much	76 8.1%	29 6.2%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	302 32.4%	127 27.1%
Week 49: a little	187 20%	68 14.5%
Week 49: quite a bit	84 9%	36 7.7%
Week 49: very much	62 6.6%	19 4.1%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	263 28.2%	90 19.2%
Week 65: a little	142 15.2%	57 12.2%
Week 65: quite a bit	71 7.6%	24 5.1%
Week 65: very much	60 6.4%	22 4.7%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	206 22.1%	74 15.8%
Week 81: a little	124 13.3%	38 8.1%
Week 81: quite a bit	57 6.1%	17 3.6%
Week 81: very much	47 5%	19 4.1%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	175 18.8%	46 9.8%
Week 97: a little	98 10.5%	28 6%
Week 97: quite a bit	47 5%	10 2.1%
Week 97: very much	45 4.8%	11 2.4%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	136 14.6%	31 6.6%
Week 113: a little	78 8.4%	27 5.8%
Week 113: quite a bit	30 3.2%	8 1.7%
Week 113: very much	31 3.3%	7 1.5%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	91 9.8%	18 3.8%
Week 129: a little	49 5.3%	16 3.4%
Week 129: quite a bit	27 2.9%	5 1.1%
Week 129: very much	25 2.7%	2 0.4%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	59 6.3%	9 1.9%
Week 145: a little	31 3.3%	9 1.9%
Week 145: quite a bit	18 1.9%	1 0.2%
Week 145: very much	8 0.9%	2 0.4%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	18 1.9%	2 0.4%
Week 161: a little	15 1.6%	3 0.6%
Week 161: quite a bit	3 0.3%	1 0.2%
Week 161: very much	4 0.4%	2 0.4%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	3 0.3%	0 0%
Week 177: a little	3 0.3%	1 0.2%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

36. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 50
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 50 are reported. Question 50 was following: "To what extent were you interested in sex?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	586 62.8%	291 62.2%
Baseline: a little	204 21.9%	101 21.6%
Baseline: quite a bit	67 7.2%	32 6.8%
Baseline: very much	27 2.9%	15 3.2%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	637 68.3%	293 62.6%
Week 17: a little	136 14.6%	92 19.7%
Week 17: quite a bit	45 4.8%	20 4.3%
Week 17: very much	21 2.3%	14 3%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	542 58.1%	251 53.6%
Week 33: a little	136 14.6%	66 14.1%
Week 33: quite a bit	37 4%	18 3.8%
Week 33: very much	22 2.4%	6 1.3%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	483 51.8%	180 38.5%
Week 49: a little	106 11.4%	50 10.7%
Week 49: quite a bit	33 3.5%	12 2.6%
Week 49: very much	13 1.4%	8 1.7%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	417 44.7%	143 30.6%
Week 65: a little	78 8.4%	37 7.9%
Week 65: quite a bit	27 2.9%	9 1.9%
Week 65: very much	14 1.5%	4 0.9%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	320 34.3%	114 24.4%
Week 81: a little	76 8.1%	24 5.1%
Week 81: quite a bit	26 2.8%	9 1.9%
Week 81: very much	12 1.3%	1 0.2%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	286 30.7%	65 13.9%
Week 97: a little	52 5.6%	19 4.1%
Week 97: quite a bit	20 2.1%	8 1.7%
Week 97: very much	7 0.8%	3 0.6%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	218 23.4%	59 12.6%
Week 113: a little	36 3.9%	11 2.4%
Week 113: quite a bit	14 1.5%	1 0.2%
Week 113: very much	7 0.8%	2 0.4%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	156 16.7%	33 7.1%
Week 129: a little	24 2.6%	6 1.3%
Week 129: quite a bit	9 1%	2 0.4%
Week 129: very much	3 0.3%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	92 9.9%	14 3%
Week 145: a little	16 1.7%	3 0.6%
Week 145: quite a bit	7 0.8%	4 0.9%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	30 3.2%	5 1.1%
Week 161: a little	5 0.5%	2 0.4%
Week 161: quite a bit	4 0.4%	1 0.2%
Week 161: very much	1 0.1%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	4 0.4%	1 0.2%
Week 177: a little	1 0.1%	0 0%
Week 177: quite a bit	1 0.1%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

37. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 51
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 51 are reported. Question 51 was following: "To what extent were you sexually active (with or without intercourse)?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	735 78.8%	374 79.9%
Baseline: a little	98 10.5%	38 8.1%
Baseline: quite a bit	41 4.4%	19 4.1%
Baseline: very much	10 1.1%	8 1.7%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	734 78.7%	354 75.6%
Week 17: a little	71 7.6%	44 9.4%
Week 17: quite a bit	24 2.6%	13 2.8%
Week 17: very much	10 1.1%	8 1.7%
Week 17: not answered	0 0%	0 0%
Week 33: not at all	642 68.8%	299 63.9%
Week 33: a little	68 7.3%	28 6%
Week 33: quite a bit	20 2.1%	9 1.9%
Week 33: very much	7 0.8%	5 1.1%
Week 33: not answered	0 0%	0 0%
Week 49: not at all	569 61%	214 45.7%
Week 49: a little	46 4.9%	26 5.6%
Week 49: quite a bit	15 1.6%	6 1.3%
Week 49: very much	5 0.5%	4 0.9%
Week 49: not answered	0 0%	0 0%
Week 65: not at all	485 52%	170 36.3%
Week 65: a little	37 4%	14 3%
Week 65: quite a bit	12 1.3%	7 1.5%
Week 65: very much	2 0.2%	2 0.4%
Week 65: not answered	0 0%	0 0%
Week 81: not at all	381 40.8%	130 27.8%
Week 81: a little	32 3.4%	13 2.8%
Week 81: quite a bit	15 1.6%	5 1.1%
Week 81: very much	6 0.6%	0 0%
Week 81: not answered	0 0%	0 0%
Week 97: not at all	333 35.7%	79 16.9%
Week 97: a little	20 2.1%	12 2.6%
Week 97: quite a bit	9 1%	4 0.9%
Week 97: very much	3 0.3%	0 0%
Week 97: not answered	0 0%	0 0%
Week 113: not at all	250 26.8%	68 14.5%
Week 113: a little	16 1.7%	3 0.6%
Week 113: quite a bit	6 0.6%	2 0.4%
Week 113: very much	3 0.3%	0 0%
Week 113: not answered	0 0%	0 0%
Week 129: not at all	176 18.9%	37 7.9%
Week 129: a little	8 0.9%	3 0.6%
Week 129: quite a bit	5 0.5%	1 0.2%
Week 129: very much	3 0.3%	0 0%
Week 129: not answered	0 0%	0 0%
Week 145: not at all	106 11.4%	17 3.6%
Week 145: a little	4 0.4%	3 0.6%
Week 145: quite a bit	5 0.5%	1 0.2%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	0 0%	0 0%
Week 161: not at all	35 3.8%	6 1.3%
Week 161: a little	3 0.3%	2 0.4%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	1 0.1%	0 0%
Week 161: not answered	0 0%	0 0%
Week 177: not at all	5 0.5%	1 0.2%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	1 0.1%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	0 0%	0 0%

38. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 52
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 52 are reported. Question 52 was following: "To what extent was sex enjoyable for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	5 0.5%	6 1.3%
Baseline: a little	23 2.5%	11 2.4%
Baseline: quite a bit	14 1.5%	5 1.1%
Baseline: very much	8 0.9%	2 0.4%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	7 0.8%	3 0.6%
Week 17: a little	13 1.4%	9 1.9%
Week 17: quite a bit	16 1.7%	11 2.4%
Week 17: very much	3 0.3%	4 0.9%
Week 17: not answered	800 85.7%	392 83.8%
Week 33: not at all	8 0.9%	4 0.9%
Week 33: a little	17 1.8%	8 1.7%
Week 33: quite a bit	11 1.2%	5 1.1%
Week 33: very much	4 0.4%	0 0%
Week 33: not answered	697 74.7%	324 69.2%
Week 49: not at all	3 0.3%	4 0.9%
Week 49: a little	6 0.6%	5 1.1%
Week 49: quite a bit	9 1%	5 1.1%
Week 49: very much	3 0.3%	4 0.9%
Week 49: not answered	614 65.8%	232 49.6%
Week 65: not at all	4 0.4%	2 0.4%
Week 65: a little	6 0.6%	4 0.9%
Week 65: quite a bit	9 1%	4 0.9%
Week 65: very much	3 0.3%	0 0%
Week 65: not answered	514 55.1%	183 39.1%
Week 81: not at all	5 0.5%	2 0.4%
Week 81: a little	7 0.8%	3 0.6%
Week 81: quite a bit	4 0.4%	2 0.4%
Week 81: very much	5 0.5%	1 0.2%
Week 81: not answered	413 44.3%	140 29.9%
Week 97: not at all	2 0.2%	2 0.4%
Week 97: a little	5 0.5%	0 0%
Week 97: quite a bit	3 0.3%	3 0.6%
Week 97: very much	3 0.3%	0 0%
Week 97: not answered	352 37.7%	90 19.2%
Week 113: not at all	0 0%	1 0.2%
Week 113: a little	5 0.5%	1 0.2%
Week 113: quite a bit	2 0.2%	0 0%
Week 113: very much	2 0.2%	0 0%
Week 113: not answered	266 28.5%	71 15.2%
Week 129: not at all	1 0.1%	0 0%
Week 129: a little	1 0.1%	0 0%
Week 129: quite a bit	1 0.1%	0 0%
Week 129: very much	1 0.1%	0 0%
Week 129: not answered	188 20.2%	41 8.8%
Week 145: not at all	1 0.1%	0 0%
Week 145: a little	0 0%	0 0%
Week 145: quite a bit	1 0.1%	1 0.2%
Week 145: very much	0 0%	0 0%
Week 145: not answered	114 12.2%	20 4.3%
Week 161: not at all	1 0.1%	0 0%
Week 161: a little	1 0.1%	0 0%
Week 161: quite a bit	0 0%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	38 4.1%	8 1.7%
Week 177: not at all	0 0%	0 0%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	6 0.6%	1 0.2%

39. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 53
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 53 are reported. Question 53 was following: "Did you have difficulty getting or maintaining an erection?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	6 0.6%	4 0.9%
Baseline: a little	19 2%	5 1.1%
Baseline: quite a bit	4 0.4%	4 0.9%
Baseline: very much	21 2.3%	11 2.4%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	10 1.1%	8 1.7%
Week 17: a little	8 0.9%	8 1.7%
Week 17: quite a bit	8 0.9%	4 0.9%
Week 17: very much	13 1.4%	7 1.5%
Week 17: not answered	800 85.7%	392 83.8%
Week 33: not at all	6 0.6%	2 0.4%
Week 33: a little	8 0.9%	6 1.3%
Week 33: quite a bit	8 0.9%	3 0.6%
Week 33: very much	18 1.9%	6 1.3%
Week 33: not answered	697 74.7%	324 69.2%
Week 49: not at all	4 0.4%	6 1.3%
Week 49: a little	6 0.6%	5 1.1%
Week 49: quite a bit	0 0%	1 0.2%
Week 49: very much	11 1.2%	6 1.3%
Week 49: not answered	614 65.8%	232 49.6%
Week 65: not at all	3 0.3%	1 0.2%
Week 65: a little	4 0.4%	4 0.9%
Week 65: quite a bit	4 0.4%	2 0.4%
Week 65: very much	11 1.2%	3 0.6%
Week 65: not answered	514 55.1%	183 39.1%
Week 81: not at all	7 0.8%	3 0.6%
Week 81: a little	2 0.2%	2 0.4%
Week 81: quite a bit	3 0.3%	2 0.4%
Week 81: very much	9 1%	1 0.2%
Week 81: not answered	413 44.3%	140 29.9%
Week 97: not at all	2 0.2%	1 0.2%
Week 97: a little	5 0.5%	1 0.2%
Week 97: quite a bit	1 0.1%	1 0.2%
Week 97: very much	5 0.5%	2 0.4%
Week 97: not answered	352 37.7%	90 19.2%
Week 113: not at all	1 0.1%	0 0%
Week 113: a little	3 0.3%	1 0.2%
Week 113: quite a bit	1 0.1%	0 0%
Week 113: very much	4 0.4%	1 0.2%
Week 113: not answered	266 28.5%	71 15.2%
Week 129: not at all	0 0%	0 0%
Week 129: a little	1 0.1%	0 0%
Week 129: quite a bit	0 0%	0 0%
Week 129: very much	3 0.3%	0 0%
Week 129: not answered	188 20.2%	41 8.8%
Week 145: not at all	1 0.1%	0 0%
Week 145: a little	0 0%	1 0.2%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	1 0.1%	0 0%
Week 145: not answered	114 12.2%	20 4.3%
Week 161: not at all	1 0.1%	0 0%
Week 161: a little	0 0%	0 0%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	38 4.1%	8 1.7%
Week 177: not at all	0 0%	0 0%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	6 0.6%	1 0.2%

40. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 54
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 54 are reported. Question 54 was following: "Did you have ejaculation problems (e.g, dry ejaculation)?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	11 1.2%	7 1.5%
Baseline: a little	14 1.5%	4 0.9%
Baseline: quite a bit	3 0.3%	2 0.4%
Baseline: very much	22 2.4%	11 2.4%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	13 1.4%	11 2.4%
Week 17: a little	5 0.5%	5 1.1%
Week 17: quite a bit	3 0.3%	1 0.2%
Week 17: very much	18 1.9%	10 2.1%
Week 17: not answered	800 85.7%	392 83.8%
Week 33: not at all	12 1.3%	10 2.1%
Week 33: a little	9 1%	1 0.2%
Week 33: quite a bit	5 0.5%	0 0%
Week 33: very much	14 1.5%	6 1.3%
Week 33: not answered	697 74.7%	324 69.2%
Week 49: not at all	7 0.8%	6 1.3%
Week 49: a little	3 0.3%	5 1.1%
Week 49: quite a bit	1 0.1%	1 0.2%
Week 49: very much	10 1.1%	6 1.3%
Week 49: not answered	614 65.8%	232 49.6%
Week 65: not at all	8 0.9%	3 0.6%
Week 65: a little	2 0.2%	1 0.2%
Week 65: quite a bit	1 0.1%	2 0.4%
Week 65: very much	11 1.2%	4 0.9%
Week 65: not answered	514 55.1%	183 39.1%
Week 81: not at all	7 0.8%	4 0.9%
Week 81: a little	0 0%	0 0%
Week 81: quite a bit	3 0.3%	0 0%
Week 81: very much	11 1.2%	4 0.9%
Week 81: not answered	413 44.3%	140 29.9%
Week 97: not at all	5 0.5%	2 0.4%
Week 97: a little	3 0.3%	0 0%
Week 97: quite a bit	0 0%	1 0.2%
Week 97: very much	5 0.5%	2 0.4%
Week 97: not answered	352 37.7%	90 19.2%
Week 113: not at all	3 0.3%	2 0.4%
Week 113: a little	1 0.1%	0 0%
Week 113: quite a bit	0 0%	0 0%
Week 113: very much	5 0.5%	0 0%
Week 113: not answered	266 28.5%	71 15.2%
Week 129: not at all	1 0.1%	0 0%
Week 129: a little	0 0%	0 0%
Week 129: quite a bit	0 0%	0 0%
Week 129: very much	3 0.3%	0 0%
Week 129: not answered	188 20.2%	41 8.8%
Week 145: not at all	2 0.2%	0 0%
Week 145: a little	0 0%	1 0.2%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	114 12.2%	20 4.3%
Week 161: not at all	1 0.1%	0 0%
Week 161: a little	0 0%	0 0%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	38 4.1%	8 1.7%
Week 177: not at all	0 0%	0 0%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	6 0.6%	1 0.2%

41. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 55
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 55 are reported. Question 55 was following: "Have you felt uncomfortable about being sexually intimate?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	933	468
Baseline: not at all	31 3.3%	13 2.8%
Baseline: a little	13 1.4%	8 1.7%
Baseline: quite a bit	4 0.4%	0 0%
Baseline: very much	2 0.2%	3 0.6%
Baseline: not answered	0 0%	0 0%
Week 17: not at all	23 2.5%	14 3%
Week 17: a little	11 1.2%	7 1.5%
Week 17: quite a bit	2 0.2%	3 0.6%
Week 17: very much	3 0.3%	3 0.6%
Week 17: not answered	800 85.7%	392 83.8%
Week 33: not at all	24 2.6%	10 2.1%
Week 33: a little	6 0.6%	4 0.9%
Week 33: quite a bit	6 0.6%	2 0.4%
Week 33: very much	4 0.4%	1 0.2%
Week 33: not answered	697 74.7%	324 69.2%
Week 49: not at all	16 1.7%	10 2.1%
Week 49: a little	4 0.4%	6 1.3%
Week 49: quite a bit	1 0.1%	1 0.2%
Week 49: very much	0 0%	1 0.2%
Week 49: not answered	614 65.8%	232 49.6%
Week 65: not at all	13 1.4%	5 1.1%
Week 65: a little	7 0.8%	3 0.6%
Week 65: quite a bit	1 0.1%	2 0.4%
Week 65: very much	1 0.1%	0 0%
Week 65: not answered	514 55.1%	183 39.1%
Week 81: not at all	13 1.4%	5 1.1%
Week 81: a little	6 0.6%	1 0.2%
Week 81: quite a bit	1 0.1%	1 0.2%
Week 81: very much	1 0.1%	1 0.2%
Week 81: not answered	413 44.3%	140 29.9%
Week 97: not at all	8 0.9%	3 0.6%
Week 97: a little	3 0.3%	2 0.4%
Week 97: quite a bit	1 0.1%	0 0%
Week 97: very much	1 0.1%	0 0%
Week 97: not answered	352 37.7%	90 19.2%
Week 113: not at all	7 0.8%	2 0.4%
Week 113: a little	0 0%	0 0%
Week 113: quite a bit	1 0.1%	0 0%
Week 113: very much	1 0.1%	0 0%
Week 113: not answered	266 28.5%	71 15.2%
Week 129: not at all	3 0.3%	0 0%
Week 129: a little	0 0%	0 0%
Week 129: quite a bit	1 0.1%	0 0%
Week 129: very much	0 0%	0 0%
Week 129: not answered	188 20.2%	41 8.8%
Week 145: not at all	2 0.2%	1 0.2%
Week 145: a little	0 0%	0 0%
Week 145: quite a bit	0 0%	0 0%
Week 145: very much	0 0%	0 0%
Week 145: not answered	114 12.2%	20 4.3%
Week 161: not at all	1 0.1%	0 0%
Week 161: a little	0 0%	0 0%
Week 161: quite a bit	1 0.1%	0 0%
Week 161: very much	0 0%	0 0%
Week 161: not answered	38 4.1%	8 1.7%
Week 177: not at all	0 0%	0 0%
Week 177: a little	0 0%	0 0%
Week 177: quite a bit	0 0%	0 0%
Week 177: very much	0 0%	0 0%
Week 177: not answered	6 0.6%	1 0.2%

42. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first). AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
AEs	808 86.6%	360 76.9%
SAEs	226 24.2%	85 18.2%

43. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events Greater Than or Equal to Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0
Description	An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first).Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
Count of Participants [Participants]	292 31.3%	109 23.3%

44. Secondary Outcome

Title	Number of Participants With Discontinuations From Study Treatment Due to Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
Count of Participants [Participants]	87 9.3%	28 6%

45. Secondary Outcome

Title	Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Hematology
Description	Hematology parameters: Haemoglobin (grams per liter [g/L]); leukocytes (log 10 raised to power 9 per liter [10*9/L]); lymphocytes (log 10 raised to power 6 per liter [10*6/L]); neutrophils (log 10 raised to power 6 per liter [10*6/L]); platelets (log 10 raised to power 9 per litre [10*9/L]).
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
Haemoglobin (Low)	12 1.3%	7 1.5%
Leukocytes (Low)	7 0.8%	7 1.5%
Lymphocytes (High)	4 0.4%	2 0.4%
Lymphocytes (Low)	44 4.7%	26 5.6%
Neutrophils (Low)	13 1.4%	4 0.9%
Platelets (Low)	3 0.3%	2 0.4%

46. Secondary Outcome

Title	Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Chemistry
Description	Chemistry parameters: Alanine aminotransferase (units per liter [U/L]); albumin (g/L); alkaline phosphatase (U/L); bilirubin (micromoles per liter [umol/L]); calcium (millimoles per liter [mmol/L]); creatine kinase (U/L); creatinine (umol/L); glucose, magnesium, phosphate, potassium, sodium (mmol/L).
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
Alanine Aminotransferase (High)	4 0.4%	1 0.2%
Albumin (Low)	7 0.8%	0 0%
Alkaline Phosphatase (High)	3 0.3%	6 1.3%
Aspartate Aminotransferase (High)	3 0.3%	1 0.2%
Bilirubin (High)	4 0.4%	1 0.2%
Calcium (High)	1 0.1%	1 0.2%
Calcium (Low)	2 0.2%	1 0.2%
Creatine Kinase (High)	4 0.4%	3 0.6%
Creatinine (High)	1 0.1%	7 1.5%
Glucose (High)	26 2.8%	8 1.7%
Glucose (Low)	5 0.5%	1 0.2%
Magnesium (High)	1 0.1%	0 0%
Magnesium (Low)	1 0.1%	0 0%
Phosphate (Low)	30 3.2%	13 2.8%
Potassium (High)	14 1.5%	5 1.1%
Potassium (Low)	0 0%	3 0.6%
Sodium (High)	2 0.2%	1 0.2%
Sodium (Low)	12 1.3%	7 1.5%

47. Secondary Outcome

Title	Number of Participants With Clinically Significant Vital Signs
Description	Vital signs included Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and heart rate.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Measure Participants	930	465
SBP	738 79.1%	328 70.1%
DBP	563 60.3%	229 48.9%
Heart rate	7 0.8%	4 0.9%

Adverse Events

Time Frame	Baseline up to 30 days after last dose of study drug or till death, whichever occurred first (up to a maximum duration of 69.8 months)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Data reported in this section was collected and analyzed only for participants who were treated with at least 1 dose of study drug.
Arm/Group Title	Enzalutamide 160 mg		Placebo		Placebo Patients Crossover to Enzalutamide 160 mg
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.		Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.		Participants who received placebo in double-blind phase and who agreed to proceed to open-label phase, received 4 capsules of Enzalutamide 40 mg each (total dose of 160 mg per day), orally once daily (up to a maximum of 18.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
All Cause Mortality
	Enzalutamide 160 mg		Placebo		Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	285/930 (30.6%)		173/465 (37.2%)		4/87 (4.6%)
Serious Adverse Events
	Enzalutamide 160 mg		Placebo		Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	372/930 (40%)		100/465 (21.5%)		12/87 (13.8%)
Blood and lymphatic system disorders
Anaemia	10/930 (1.1%)		1/465 (0.2%)		1/87 (1.1%)
Anaemia macrocytic	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Haemolytic anaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Thrombocytopenia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Neutropenia	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Normochromic normocytic anaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Splenic haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cardiac disorders
Acute coronary syndrome	6/930 (0.6%)		2/465 (0.4%)		0/87 (0%)
Acute myocardial infarction	10/930 (1.1%)		2/465 (0.4%)		1/87 (1.1%)
Angina pectoris	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Angina unstable	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Aortic valve incompetence	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Aortic valve stenosis	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Arrhythmia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Atrial fibrillation	9/930 (1%)		3/465 (0.6%)		0/87 (0%)
Atrial flutter	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Atrioventricular block complete	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bradycardia	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Cardiac arrest	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Cardiac failure	10/930 (1.1%)		0/465 (0%)		0/87 (0%)
Cardio-respiratory arrest	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Conduction disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Coronary artery disease	8/930 (0.9%)		0/465 (0%)		0/87 (0%)
Left ventricular failure	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Mitral valve incompetence	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Myocardial infarction	10/930 (1.1%)		0/465 (0%)		0/87 (0%)
Myocardial ischaemia	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Pericardial effusion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Right ventricular failure	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Sick sinus syndrome	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Sinus bradycardia	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Ventricular arrhythmia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Ventricular extrasystoles	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Atrioventricular block second degree	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cardiac aneurysm	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cardiac failure acute	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Cardiac failure congestive	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cardiogenic shock	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cardiovascular insufficiency	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Left ventricular dysfunction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pericarditis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Sinus arrest	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Tricuspid valve disease	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Ventricular tachycardia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Congenital, familial and genetic disorders
Phimosis	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Ear and labyrinth disorders
Vertigo	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Eye disorders
Cataract	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastrointestinal disorders
Abdominal hernia	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Abdominal pain	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Acquired oesophageal web	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Constipation	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Diarrhoea	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Duodenal stenosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Duodenal ulcer haemorrhage	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Dysphagia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Faecaloma	1/930 (0.1%)		2/465 (0.4%)		0/87 (0%)
Gastric haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastrointestinal mucosal disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hiatus hernia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Ileus	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Inguinal hernia	4/930 (0.4%)		3/465 (0.6%)		0/87 (0%)
Intestinal congestion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Intestinal ischaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Large intestinal stenosis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Melaena	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Mesenteric vein thrombosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Nausea	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Oesophageal varices haemorrhage	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Peptic ulcer	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Peptic ulcer haemorrhage	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Pharyngo-oesophageal diverticulum	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Small intestinal haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Small intestinal obstruction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Upper gastrointestinal haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Rectal haemorrhage	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Abdominal distension	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Colitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Colonic pseudo-obstruction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastritis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastrointestinal haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastrointestinal necrosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Inguinal hernia strangulated	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Intestinal obstruction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lower gastrointestinal haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Periproctitis	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Volvulus	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
General disorders
Asthenia	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Chest pain	7/930 (0.8%)		1/465 (0.2%)		0/87 (0%)
Death	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Device occlusion	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Disease progression	3/930 (0.3%)		0/465 (0%)		1/87 (1.1%)
Fatigue	4/930 (0.4%)		1/465 (0.2%)		0/87 (0%)
General physical health deterioration	3/930 (0.3%)		0/465 (0%)		1/87 (1.1%)
Non-cardiac chest pain	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Oedema peripheral	0/930 (0%)		2/465 (0.4%)		0/87 (0%)
Pain	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Pyrexia	3/930 (0.3%)		2/465 (0.4%)		0/87 (0%)
Stent-graft endoleak	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Sudden death	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Vessel puncture site haematoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Malaise	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Performance status decreased	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Sudden cardiac death	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Swelling	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hepatobiliary disorders
Cholangitis acute	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Cholecystitis	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Cholecystitis acute	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cholelithiasis	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Hepatic cirrhosis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Hepatic failure	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bile duct stone	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Biliary colic	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cholelithiasis obstructive	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hepatic function abnormal	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Immune system disorders
Anaphylactic reaction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Anaphylactic shock	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Iodine allergy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Infections and infestations
Appendicitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Arthritis bacterial	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bacteraemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Biliary tract infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bronchitis	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Bronchopneumonia	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cellulitis	6/930 (0.6%)		1/465 (0.2%)		0/87 (0%)
Diverticulitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Enterocolitis infectious	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastroenteritis	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Herpes zoster	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Infection	0/930 (0%)		1/465 (0.2%)		1/87 (1.1%)
Lower respiratory tract infection	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Lung infection	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Pneumonia	20/930 (2.2%)		2/465 (0.4%)		0/87 (0%)
Pneumonia bacterial	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pyelonephritis	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Respiratory tract infection	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Septic shock	3/930 (0.3%)		0/465 (0%)		1/87 (1.1%)
Sinusitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Skin infection	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Small intestine gangrene	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Soft tissue infection	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Tracheobronchitis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Upper respiratory tract infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Urinary tract infection	11/930 (1.2%)		6/465 (1.3%)		0/87 (0%)
Urosepsis	9/930 (1%)		1/465 (0.2%)		0/87 (0%)
Viral diarrhoea	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Viral infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Sepsis	6/930 (0.6%)		0/465 (0%)		0/87 (0%)
Pyelonephritis acute	0/930 (0%)		2/465 (0.4%)		0/87 (0%)
Bacterial sepsis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cystitis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Device related infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Diarrhoea infectious	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Erysipelas	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lobar pneumonia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Nail bed infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Peritonsillar abscess	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Tooth infection	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Injury, poisoning and procedural complications
Ankle fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Clavicle fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Comminuted fracture	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Concussion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cystitis radiation	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Excoriation	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Fall	12/930 (1.3%)		2/465 (0.4%)		0/87 (0%)
Femoral neck fracture	6/930 (0.6%)		0/465 (0%)		0/87 (0%)
Femur fracture	5/930 (0.5%)		1/465 (0.2%)		0/87 (0%)
Fibula fracture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Forearm fracture	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Fracture	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Heat stroke	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hip fracture	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Humerus fracture	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Infusion related reaction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lumbar vertebral fracture	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Patella fracture	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Pelvic fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Pubis fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Radius fracture	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Rib fracture	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Spinal fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Subdural haematoma	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Tendon rupture	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Tibia fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Ulna fracture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Upper limb fracture	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Urostomy complication	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Venous injury	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Spinal compression fracture	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Thoracic vertebral fracture	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cervical vertebral fracture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Chemical cystitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Facial bones fracture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Laceration	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Toxicity to various agents	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Investigations
Alanine aminotransferase increased	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Blood creatinine increased	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Blood pressure decreased	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Blood urea increased	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Haemoglobin decreased	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
International normalised ratio increased	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Metabolism and nutrition disorders
Dehydration	4/930 (0.4%)		1/465 (0.2%)		0/87 (0%)
Haemochromatosis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Hyperkalaemia	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Hyponatraemia	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Decreased appetite	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Type 2 diabetes mellitus	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Back pain	1/930 (0.1%)		3/465 (0.6%)		0/87 (0%)
Bone pain	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cervical spinal stenosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Flank pain	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Intervertebral disc protrusion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lumbar spinal stenosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Mobility decreased	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Muscular weakness	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Musculoskeletal pain	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Osteoarthritis	5/930 (0.5%)		3/465 (0.6%)		1/87 (1.1%)
Osteonecrosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pathological fracture	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Rheumatoid arthritis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Rotator cuff syndrome	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Spinal column stenosis	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Arthralgia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Osteoporotic fracture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pain in extremity	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Adenocarcinoma of colon	6/930 (0.6%)		2/465 (0.4%)		0/87 (0%)
Basal cell carcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bladder cancer	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Bladder neoplasm	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bladder papilloma	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Bladder transitional cell carcinoma	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Brain neoplasm	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Chronic lymphocytic leukaemia	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Colon cancer	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Colorectal adenocarcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Gastric cancer	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Malignant neoplasm of unknown primary site	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Mesothelioma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Metastases to bone	2/930 (0.2%)		2/465 (0.4%)		0/87 (0%)
Metastases to liver	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Metastases to lymph nodes	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Metastases to peritoneum	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Metastases to rectum	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Metastases to spine	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Metastatic neoplasm	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Neoplasm	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Neoplasm progression	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Non-Hodgkin's lymphoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Non-small cell lung cancer	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pancreatic carcinoma metastatic	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Pituitary tumour benign	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Prostate cancer metastatic	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Rectal adenocarcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Rectal adenoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Small cell lung cancer	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Small intestine adenocarcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Transitional cell carcinoma	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Waldenstrom's macroglobulinaemia	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Prostate cancer	2/930 (0.2%)		1/465 (0.2%)		0/87 (0%)
Clear cell renal cell carcinoma	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Squamous cell carcinoma of skin	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Bladder cancer recurrent	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Glioblastoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hypopharyngeal cancer	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Laryngeal cancer recurrent	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Laryngeal squamous cell carcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lung adenocarcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lung cancer metastatic	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Malignant melanoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Neuroendocrine carcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pancreatic carcinoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Nervous system disorders
Carotid artery occlusion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Carotid artery stenosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cerebral haemorrhage	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cerebral infarction	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Cerebral ischaemia	0/930 (0%)		2/465 (0.4%)		0/87 (0%)
Cerebrovascular accident	7/930 (0.8%)		1/465 (0.2%)		0/87 (0%)
Cognitive disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Convulsion	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cranial nerve disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Diplegia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Encephalopathy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Grand mal convulsion	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Ischaemic stroke	6/930 (0.6%)		1/465 (0.2%)		0/87 (0%)
Lacunar infarction	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lethargy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Loss of consciousness	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Presyncope	3/930 (0.3%)		0/465 (0%)		0/87 (0%)
Spinal cord compression	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Syncope	7/930 (0.8%)		2/465 (0.4%)		1/87 (1.1%)
Transient ischaemic attack	5/930 (0.5%)		1/465 (0.2%)		0/87 (0%)
Haemorrhagic stroke	1/930 (0.1%)		0/465 (0%)		1/87 (1.1%)
Headache	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Aphasia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Basal ganglia haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Dementia	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Lumbar radiculopathy	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Neuralgia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Sciatica	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Vertigo CNS origin	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Psychiatric disorders
Anxiety	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Depression	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Mania	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Alcohol abuse	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Confusional state	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Renal and urinary disorders
Azotaemia	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Bladder disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bladder hypertrophy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Bladder obstruction	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Bladder outlet obstruction	1/930 (0.1%)		2/465 (0.4%)		0/87 (0%)
Calculus bladder	2/930 (0.2%)		2/465 (0.4%)		0/87 (0%)
Calculus ureteric	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Cystitis haemorrhagic	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Cystitis noninfective	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Haematuria	31/930 (3.3%)		15/465 (3.2%)		1/87 (1.1%)
Hydronephrosis	5/930 (0.5%)		3/465 (0.6%)		1/87 (1.1%)
Hypertonic bladder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Nephrolithiasis	5/930 (0.5%)		2/465 (0.4%)		0/87 (0%)
Obstructive uropathy	0/930 (0%)		3/465 (0.6%)		0/87 (0%)
Postrenal failure	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Renal colic	2/930 (0.2%)		2/465 (0.4%)		0/87 (0%)
Renal failure	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Renal failure acute	7/930 (0.8%)		8/465 (1.7%)		0/87 (0%)
Renal failure chronic	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Renal impairment	1/930 (0.1%)		2/465 (0.4%)		0/87 (0%)
Renal pain	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Ureteric obstruction	2/930 (0.2%)		2/465 (0.4%)		1/87 (1.1%)
Ureteric stenosis	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Urethral obstruction	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Urethral stenosis	1/930 (0.1%)		3/465 (0.6%)		0/87 (0%)
Urinary fistula	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Urinary incontinence	3/930 (0.3%)		1/465 (0.2%)		0/87 (0%)
Urinary retention	13/930 (1.4%)		12/465 (2.6%)		0/87 (0%)
Urinary tract obstruction	4/930 (0.4%)		2/465 (0.4%)		0/87 (0%)
Vesical fistula	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Anuria	0/930 (0%)		0/465 (0%)		1/87 (1.1%)
Stress urinary incontinence	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Urinary bladder haemorrhage	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Urinary tract disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Penile pain	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Prostatic cyst	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Prostatic haemorrhage	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Prostatic obstruction	0/930 (0%)		1/465 (0.2%)		0/87 (0%)
Prostatomegaly	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Prostatitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Choking	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Chronic obstructive pulmonary disease	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Dyspnoea	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Interstitial lung disease	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Laryngeal oedema	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pleural effusion	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Pleurisy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pneumonia aspiration	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Pulmonary embolism	4/930 (0.4%)		3/465 (0.6%)		0/87 (0%)
Epistaxis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Lung disorder	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pneumonitis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Pulmonary oedema	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Surgical and medical procedures
Bladder calculus removal	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Cystoprostatectomy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Transurethral prostatectomy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Vascular disorders
Aortic aneurysm	4/930 (0.4%)		0/465 (0%)		0/87 (0%)
Aortic dissection	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Aortic stenosis	1/930 (0.1%)		1/465 (0.2%)		0/87 (0%)
Deep vein thrombosis	1/930 (0.1%)		2/465 (0.4%)		0/87 (0%)
Haemorrhage	2/930 (0.2%)		0/465 (0%)		0/87 (0%)
Hypertension	5/930 (0.5%)		0/465 (0%)		0/87 (0%)
Ischaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Peripheral arterial occlusive disease	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Peripheral artery stenosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Peripheral ischaemia	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Thrombosis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Angiopathy	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Aortic rupture	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Haematoma	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Hypertensive crisis	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Venous thrombosis limb	1/930 (0.1%)		0/465 (0%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Enzalutamide 160 mg		Placebo		Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	762/930 (81.9%)		299/465 (64.3%)		45/87 (51.7%)
Blood and lymphatic system disorders
Anaemia	63/930 (6.8%)		20/465 (4.3%)		7/87 (8%)
Gastrointestinal disorders
Constipation	121/930 (13%)		39/465 (8.4%)		1/87 (1.1%)
Diarrhoea	112/930 (12%)		47/465 (10.1%)		3/87 (3.4%)
Nausea	125/930 (13.4%)		42/465 (9%)		3/87 (3.4%)
General disorders
Asthenia	94/930 (10.1%)		32/465 (6.9%)		10/87 (11.5%)
Fatigue	348/930 (37.4%)		73/465 (15.7%)		13/87 (14.9%)
Oedema peripheral	59/930 (6.3%)		23/465 (4.9%)		4/87 (4.6%)
Infections and infestations
Urinary tract infection	70/930 (7.5%)		33/465 (7.1%)		1/87 (1.1%)
Injury, poisoning and procedural complications
Fall	164/930 (17.6%)		25/465 (5.4%)		2/87 (2.3%)
Rib fracture	64/930 (6.9%)		7/465 (1.5%)		1/87 (1.1%)
Investigations
Weight decreased	80/930 (8.6%)		11/465 (2.4%)		4/87 (4.6%)
Metabolism and nutrition disorders
Decreased appetite	108/930 (11.6%)		22/465 (4.7%)		3/87 (3.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	119/930 (12.8%)		36/465 (7.7%)		3/87 (3.4%)
Back pain	120/930 (12.9%)		38/465 (8.2%)		4/87 (4.6%)
Musculoskeletal pain	61/930 (6.6%)		15/465 (3.2%)		1/87 (1.1%)
Pain in extremity	56/930 (6%)		15/465 (3.2%)		2/87 (2.3%)
Nervous system disorders
Dizziness	112/930 (12%)		27/465 (5.8%)		6/87 (6.9%)
Headache	103/930 (11.1%)		23/465 (4.9%)		3/87 (3.4%)
Renal and urinary disorders
Haematuria	97/930 (10.4%)		41/465 (8.8%)		2/87 (2.3%)
Urinary retention	43/930 (4.6%)		36/465 (7.7%)		0/87 (0%)
Pollakiuria	43/930 (4.6%)		25/465 (5.4%)		0/87 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	48/930 (5.2%)		15/465 (3.2%)		1/87 (1.1%)
Vascular disorders
Hot flush	132/930 (14.2%)		38/465 (8.2%)		3/87 (3.4%)
Hypertension	161/930 (17.3%)		27/465 (5.8%)		6/87 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.