Trial Outcomes & Findings for Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (NCT NCT00974311)

Last Updated: 2018-12-11

Results Overview

Survival was defined as time from randomization to death due to any cause. The duration of overall survival was right-censored for participants who were lost to follow-up since randomization or not known to have died at the data analysis cut-off date (this included participants who were known to have died after the data analysis cut-off date).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1199 participants

Primary outcome timeframe

During study period (up to 101 months)

Results posted on

2018-12-11

Participant Flow

A total of 1199 participants were enrolled and randomized for double-blind (DB) phase. Out of which, 159 participants entered the optional open-label extension (OLE) phase.

Participants were randomized 2:1 to receive either Enzalutamide or Placebo in DB phase. All participants who continued in OLE phase, received Enzalutamide.

Participant milestones

Participant milestones
Measure	Enzalutamide In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).
DB Phase (up to 24 Months) STARTED	800	399
DB Phase (up to 24 Months) COMPLETED	109	50
DB Phase (up to 24 Months) NOT COMPLETED	691	349
OLE Phase (up to 77 Months) STARTED	109	50
OLE Phase (up to 77 Months) COMPLETED	0	0
OLE Phase (up to 77 Months) NOT COMPLETED	109	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzalutamide In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).
DB Phase (up to 24 Months) Lost to Follow-up	5	2
DB Phase (up to 24 Months) Death	561	298
DB Phase (up to 24 Months) Withdrawal by Subject	16	7
DB Phase (up to 24 Months) Study Terminated by Sponsor	108	42
DB Phase (up to 24 Months) Other	1	0
OLE Phase (up to 77 Months) Death	14	21
OLE Phase (up to 77 Months) Study Terminated by Sponsor	78	26
OLE Phase (up to 77 Months) Other	15	2
OLE Phase (up to 77 Months) Withdrawal by Subject	2	1

Baseline Characteristics

Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Total n=1199 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	232 Participants n=5 Participants	130 Participants n=7 Participants	362 Participants n=5 Participants
Age, Categorical >=65 years	568 Participants n=5 Participants	269 Participants n=7 Participants	837 Participants n=5 Participants
Age, Continuous	68.8 years STANDARD_DEVIATION 7.96 • n=5 Participants	68.6 years STANDARD_DEVIATION 8.39 • n=7 Participants	68.7 years STANDARD_DEVIATION 8.11 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	800 Participants n=5 Participants	399 Participants n=7 Participants	1199 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	23 Participants n=7 Participants	55 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	768 Participants n=5 Participants	376 Participants n=7 Participants	1144 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	27 Participants n=5 Participants	20 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) White	745 Participants n=5 Participants	366 Participants n=7 Participants	1111 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	21 Participants n=5 Participants	4 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	181 Participants n=5 Participants	107 Participants n=7 Participants	288 Participants n=5 Participants
Region of Enrollment Spain	23 Participants n=5 Participants	13 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment Austria	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Chile	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United Kingdom	82 Participants n=5 Participants	50 Participants n=7 Participants	132 Participants n=5 Participants
Region of Enrollment Italy	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment France	193 Participants n=5 Participants	80 Participants n=7 Participants	273 Participants n=5 Participants
Region of Enrollment Canada	82 Participants n=5 Participants	25 Participants n=7 Participants	107 Participants n=5 Participants
Region of Enrollment Argentina	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Belgium	27 Participants n=5 Participants	18 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Poland	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Australia	60 Participants n=5 Participants	33 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment South Africa	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Germany	62 Participants n=5 Participants	24 Participants n=7 Participants	86 Participants n=5 Participants
Region of Enrollment Netherlands	32 Participants n=5 Participants	14 Participants n=7 Participants	46 Participants n=5 Participants

PRIMARY outcome

Timeframe: During study period (up to 101 months)

Population: ITT included all participants who were randomized into the study.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Overall Survival	18.4 Months Interval 17.3 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment	13.6 Months Interval 11.3 to 15.8	—

SECONDARY outcome

Timeframe: During DB phase (up to 24 months)

Population: ITT included all participants who were randomized into the study.

Radiographic progression-free survival was defined as time from randomization to the earliest objective evidence of radiographic progression or death due to any cause. Participants were assessed for objective disease progression at regularly scheduled visits. The consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2 were taken into consideration for the determination of disease progression. Radiographic disease progression was defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for soft tissue disease, or the appearance of two or more new bone lesions on bone scan. Progression at the first scheduled reassessment at Week 13 required a confirmatory scan 6 or more weeks later. Participants who did not reach the endpoint were right censored at their last assessment.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Radiographic Progression-free Survival	8.3 Months Interval 8.2 to 9.4	2.9 Months Interval 2.8 to 3.4	—

SECONDARY outcome

Timeframe: During DB Phase (up to 24 months)

Population: ITT included all participants who were randomized into the study.

The time to first skeletal-related event was defined as time from randomization to the occurrence of the first skeletal-related event. Participants were assessed for skeletal-related events at regularly scheduled visits. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. Participants who did not reach the endpoint were right censored at their last assessment.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Time to First Skeletal-related Event	16.7 Months Interval 14.6 to 19.1	13.3 Months Interval 9.9 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment	—

SECONDARY outcome

Timeframe: Baseline up to 24 months

Population: Evaluable intent to treat (ITT) - all participants who were part of the ITT population and had a global FACT-P score at baseline and at least 1 post-baseline assessment.

The FACT-P was a 39-item participant questionnaire which assessed physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items were scored from 0 (not at all) to 4 (very much). The sum of scores on all 5 domains constitutes the global FACT-P. The global/total FACT-P score ranged from 0 (worst) to 156 (best), higher scores indicate better health status. Responders were those participants who had a 10-point improvement in their total FACT-P score, as compared with baseline, on two consecutive measurements obtained at least 3 weeks apart.

Outcome measures

Outcome measures
Measure	Enzalutamide n=651 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=257 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P)	43.2 Percentage of participants Interval 39.3 to 47.1	18.3 Percentage of participants Interval 13.8 to 23.6	—

SECONDARY outcome

Timeframe: Baseline and at every study visit from Week 13 while on study drug (up to 24 months)

Population: ITT included all participants who were randomized into the study.

Time to PSA progression was defined as time from randomization to PSA progression. Participants who did not reach the endpoint were right censored at their last assessment or for participants with no post-baseline PSA assessment, date of randomization. For participants with PSA declines at Week 13, the PSA progression date was defined as the date that a \>=25% increase and an absolute increase of \>=2 nanogram per milliliter (ng/mL) above the nadir was documented, which was confirmed by a second consecutive value obtained 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment). For participants with no PSA declines at Week 13, PSA progression date was defined as the date that a \>=25% increase and an absolute increase of \>=2 ng/mL above the baseline was documented, which was confirmed by a second consecutive value 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment).

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Time to Prostate-specific Antigen (PSA) Progression	8.3 Months Interval 5.8 to 8.3	3.0 Months Interval 2.9 to 3.7	—

SECONDARY outcome

Timeframe: Baseline up to 24 months

Population: Evaluable ITT Population included participants with metastatic bone disease at baseline; provided answers to Question #3 of the Brief Pain Inventory - Short Form for a minimum of 4 out of 7 days in the baseline run-in period; stable baseline pain; stable analgesic use; and had an average pain score during the baseline run-in period of \>= 4.

The proportion of participants with pain palliation was assessed for participants with a stable and sufficient pain burden at study entry. Pain burden was measured by question #3 of the Brief Pain Inventory (Short Form). This scale measures pain on a 0 to 10 scale with 0 indicating no pain and 10 indicating pain as bad as you can imagine. Pain palliation at Week 13 was determined for the proportion of men with baseline bone metastasis(es) who had baseline pain attributable to the metastasis(es). Palliation was defined as \>=30% reduction in average pain score at Week 13 compared to baseline without a \>=30% increase in analgesic use.

Outcome measures

Outcome measures
Measure	Enzalutamide n=49 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=15 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Percentage of Participants With Pain Palliation	44.9 Percentage of participants Interval 30.7 to 59.8	6.7 Percentage of participants Interval 0.2 to 31.9	—

SECONDARY outcome

Timeframe: During DB phase (up to 24 months)

Population: Evaluable ITT population included participants who were part of the ITT Population and had a PSA level measured at baseline and at least 1 post-baseline assessment.

Participants were evaluable for PSA response rate if they had a PSA level measured at baseline and at least 1 post-baseline assessment. Both PSA responses of \> 50% and \> 90% were determined. PSA responses required confirmation with a subsequent assessment that was conducted at least 3 weeks later.

Outcome measures

Outcome measures
Measure	Enzalutamide n=731 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=330 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Percentage of Participants With Prostate Specific Antigen (PSA) Response Decline >=50% from baseline	54 Percentage of participants	2 Percentage of participants	—
Percentage of Participants With Prostate Specific Antigen (PSA) Response Decline >=90% from baseline	25 Percentage of participants	1 Percentage of participants	—

SECONDARY outcome

Timeframe: During DB phase (up to 24 months)

Population: ITT with measurable disease population included participants who were part of the ITT Population and had measurable soft tissue disease at screening, defined by at least 1 target lesion according to RECIST v1.1.

The best overall soft tissue response as assessed using RECIST v1.1 during the study was summarized using the investigators' response assessments and also the derived response assessments by treatment group. Only participants with measurable soft tissue disease at screening were included in this analysis. Participants with measurable disease at screening are participants who had at least 1 target lesion identified per RECIST v1.1 at screening. Percentage of participants summarizes the number of participants with complete or partial objective response (%). Soft Tissue assessment based on Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228-247.

Outcome measures

Outcome measures
Measure	Enzalutamide n=446 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=208 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Percentage of Participants With Soft-tissue Objective Response	29 Percentage of participants	4 Percentage of participants	—

SECONDARY outcome

Timeframe: Week 13

Population: Evaluable ITT included participants who were part of the ITT Population and who were evaluable for EQ-5D.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Five parameters (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were assessed on 3-point categorical scale (1= no problems, 2= some/moderate problems and 3= severe problem). Score were transformed and resulted in a total EQ-5D score range of 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better health and quality of life.

Outcome measures

Outcome measures
Measure	Enzalutamide n=126 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=55 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
European Quality of Life Five-Domain (EQ-5D) Scale	67.2 units on a scale Standard Deviation 19.29	60.0 units on a scale Standard Deviation 19.26	—

SECONDARY outcome

Timeframe: Baseline up to 24 months

Population: CTC evaluable population included participants with a baseline and at least 1 post baseline CTC assessment.

CTC conversion was assessed for participants with baseline CTC counts of greater than or equal to (\>=) 5 cells per 7.5 milliliter (mL) of blood. A CTC conversion was defined as a decline in the CTC count to less than (\<) 5 cells per 7.5 mL of blood. In this outcome measure percentage of participants with CTC conversion was reported.

Outcome measures

Outcome measures
Measure	Enzalutamide n=127 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=62 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Percentage of Participants With Circulating Tumor Cell (CTC) Conversion	48 percentage of participants Interval 39.09 to 57.07	9.7 percentage of participants Interval 3.63 to 19.88	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months)

Population: Safety population was defined as all randomized participants who received at least 1 dose of study drug.

AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes or deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events which occurred between first dose of study drug and up to the safety follow-up visit or the initiation of another anti-neoplastic therapy, whichever occurred first (up to 101 months). AEs included both serious and non-serious AEs. Clinically significant physical examination abnormalities were reported as AEs. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase n=50 Participants Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) AEs	789 Participants	390 Participants	48 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	319 Participants	155 Participants	25 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months)

Population: Safety population was defined as all randomized participants who received at least 1 dose of study drug.

Criteria for abnormalities in vital signs included: sitting/supine systolic blood pressure (SBP) values: absolute result greater than (\>) 180 millimeter of mercury (mmHg) and \>40 mmHg increase from baseline (BL) and less than (\<) 90 mmHg and \>30 mmHg decrease from BL; diastolic blood pressure (DBP) values: absolute result \>105 mmHg and \>30 mmHg increase from BL and absolute result \< 50 mmHg and \>20 mmHg decrease from BL; any abnormalities in SBP or DBP; heart rate values: absolute result \> 120 beats per minute (bpm) and \>30 bpm increase from BL and absolute result \< 50 bpm and \>20 bpm decrease from BL or any abnormalities in heart rate. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase n=50 Participants Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Number of Participants With Clinically Significant Changes in Vital Signs SBP: >180 mmHg and >40 mmHg Increase from BL	28 Participants	7 Participants	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs SBP: < 90 mmHg and >30 mmHg Decrease from BL	13 Participants	5 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs DBP: >105 mmHg and >30 mmHg Increase from BL	5 Participants	2 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs DBP: < 50 mmHg and >20 mmHg Decrease from BL	13 Participants	3 Participants	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Any abnormalities in SBP or DBP	52 Participants	16 Participants	2 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate: > 120 bpm and >30 bpm Increase from BL	7 Participants	5 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate: < 50 bpm and >20 bpm Decrease from BL	18 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Any abnormalities in Heart Rate	25 Participants	6 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to the end of DB phase or unscheduled visit (up to 24 months)

Population: Safety population was defined as all randomized participants who received at least 1 dose of study drug.

Any new post baseline abnormality was defined as any abnormal ECG finding that appeared after baseline assessment which was not seen at the screening or baseline ECG assessment. Where, criteria of abnormality was QTcF interval \> 470 millisecond (msec). Participants were counted once only for a specific abnormality. This outcome measure was planned to be analysed in double blind phase only. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Number of Participants With Any Newly Clinically Significant Abnormal Finding in Electrocardiogram (ECG)	28 Participants	13 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months)

Population: Safety population was defined as all randomized participants who received at least 1 dose of study drug.

Laboratory parameters included hematological and chemistry parameters. Chemistry parameters included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, creatine kinase, creatinine, glucose, magnesium, phosphate, potassium and sodium. Hematology parameters included haemoglobin, leukocytes, lymphocytes, neutrophils and platelet. Test abnormalities were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 as Grade 3= severe and Grade 4= life-threatening or disabling. Only categories with at least 1 participant with abnormality are reported in this outcome measure. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.

Outcome measures

Outcome measures
Measure	Enzalutamide n=800 Participants In DB Phase, participants received Enzalutamide capsules 160 mg orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received same treatment until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 8.3 months).	Placebo n=399 Participants In DB Phase, participants received placebo capsules (for Enzalutamide) orally per day. Participants who completed DB Phase, entered in optional OLE Phase and received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 3.0 months in DB Phase and 7.7 months in OLE Phase).	Placebo (DB) /Enzalutamide 160 mg (OLE) Phase n=50 Participants Participants who received placebo in DB phase, completed DB Phase and entered in optional OLE Phase, received Enzalutamide capsules 160 mg orally per day until unacceptable toxicity, confirmed disease progression and the participant was scheduled to initiate a new systemic anti-neoplastic therapy, death or withdrawal (median treatment duration was 7.7 months).
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Alkaline Phosphatase: High	102 Participants	74 Participants	3 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Aspartate Aminotransferase: High	3 Participants	4 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Bilirubin: High	2 Participants	0 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Calcium: Low	14 Participants	15 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Calcium: High	1 Participants	0 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Magnesium: Low	0 Participants	1 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Magnesium: High	1 Participants	1 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Potassium: Low	7 Participants	4 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Potassium: High	2 Participants	3 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Sodium: Low	19 Participants	13 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Sodium: High	0 Participants	1 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Hemoglobin: Low	38 Participants	20 Participants	4 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Hemoglobin: High	1 Participants	0 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Leukocytes: Low	8 Participants	1 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Lymphocytes: Low	80 Participants	48 Participants	5 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Neutrophils: Low	10 Participants	0 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Platelet; Low	4 Participants	4 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Alanine Aminotransferase:High	2 Participants	2 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Albumin: Low	7 Participants	3 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Creatine Kinase: High	4 Participants	2 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Creatinine: High	0 Participants	2 Participants	0 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Glucose: High	17 Participants	10 Participants	1 Participants
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) Phosphate: Low	28 Participants	10 Participants	2 Participants

Adverse Events

Enzalutamide: DB + OLE Phase

Serious events: 319 serious events

Other events: 784 other events

Deaths: 0 deaths

Placebo: DB Phase

Serious events: 155 serious events

Other events: 385 other events

Deaths: 0 deaths

Placebo (DB) /Enzalutamide 160 mg (OLE) Phase

Serious events: 25 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER