Trial Outcomes & Findings for An Asian Study to Evaluate Efficacy and Safety of Oral Enzalutamide in Progressive Metastatic Prostate Cancer Participants (NCT NCT02294461)

Last Updated: 2025-10-24

Results Overview

The time to Prostate Specific Antigen (PSA) progression was defined as the time from randomization to the PSA progression. The PSA progression was defined according to the consensus guidelines of Prostate Cancer Clinical Trials Working Group 2 (PCWG2).For participants with PSA decline at Week 13, the PSA progression date was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which would be confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at Week 13, the PSA progression date was defined as the date when 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. Time to PSA progression was estimated using the Kaplan-Meier method. Participants without confirmed PSA progression were censored.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

395 participants

Primary outcome timeframe

From the date of randomization to PSA progression median follow-up time is 6.47 months for enzalutamide and 2.99 months for placebo

Results posted on

2025-10-24

Participant Flow

The study population consisted of men with asymptomatic or mildly symptomatic progressive metastatic prostate cancer, who had failed androgen deprivation therapy, and have not been treated with cytotoxic chemotherapy. Participants from 46 study sites in 4 countries (China, Korea, Taiwan and Hong Kong) were randomized for the study.

Participants who met inclusion criteria and none of the exclusion criteria were enrolled in the study.

Participant milestones

Participant milestones
Measure	Enzalutamide Participants received 160 milligrams (mg) of enzalutamide orally once a day during double blind period until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	Placebo Patients Crossover to Enzalutamide 160 mg Eligible participants who received enzalutamide matching placebo during Double Blind period and who provided consent to take part in Open label period, received 160 mg of enzalutamide orally once a day during open-label period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 53.8 months).
Double-blind Period (up to 29.4 Months) STARTED	202	193	0
Double-blind Period (up to 29.4 Months) Treated/Received Study Drug	202	193	0
Double-blind Period (up to 29.4 Months) COMPLETED	84	1	0
Double-blind Period (up to 29.4 Months) NOT COMPLETED	118	192	0
Open-label Period (up to 54.3 Months) STARTED	85	0	51
Open-label Period (up to 54.3 Months) COMPLETED	0	0	0
Open-label Period (up to 54.3 Months) NOT COMPLETED	85	0	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzalutamide Participants received 160 milligrams (mg) of enzalutamide orally once a day during double blind period until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	Placebo Patients Crossover to Enzalutamide 160 mg Eligible participants who received enzalutamide matching placebo during Double Blind period and who provided consent to take part in Open label period, received 160 mg of enzalutamide orally once a day during open-label period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 53.8 months).
Double-blind Period (up to 29.4 Months) Death	6	4	0
Double-blind Period (up to 29.4 Months) Miscellaneous	30	66	0
Double-blind Period (up to 29.4 Months) Withdrawal by Subject	27	54	0
Double-blind Period (up to 29.4 Months) Protocol Deviation	0	2	0
Double-blind Period (up to 29.4 Months) Lost to Follow-up	1	0	0
Double-blind Period (up to 29.4 Months) Progressive Disease	38	51	0
Double-blind Period (up to 29.4 Months) Adverse Event	16	15	0
Open-label Period (up to 54.3 Months) Miscellaneous	28	0	16
Open-label Period (up to 54.3 Months) Withdrawal by Subject	19	0	10
Open-label Period (up to 54.3 Months) Protocol Deviation	2	0	0
Open-label Period (up to 54.3 Months) Lost to Follow-up	4	0	2
Open-label Period (up to 54.3 Months) Progressive Disease	20	0	12
Open-label Period (up to 54.3 Months) Death	6	0	5
Open-label Period (up to 54.3 Months) Adverse Event	6	0	6

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzalutamide n=202 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=193 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months). Eligible participants who received enzalutamide matching placebo during double-blind period and who provided consent to take part in open-label period, received 160 mg of enzalutamide orally once a day during open-label period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 53.8 months).	Total n=395 Participants Total of all reporting groups
Age, Continuous	71.6 Years STANDARD_DEVIATION 8.1 • n=202 Participants	71 Years STANDARD_DEVIATION 8.7 • n=193 Participants	71.3 Years STANDARD_DEVIATION 8.4 • n=395 Participants
Sex: Female, Male Female	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Sex: Female, Male Male	202 Participants n=202 Participants	193 Participants n=193 Participants	395 Participants n=395 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race (NIH/OMB) Asian	202 Participants n=202 Participants	193 Participants n=193 Participants	395 Participants n=395 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race (NIH/OMB) Black or African American	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race (NIH/OMB) White	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race (NIH/OMB) More than one race	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=202 Participants	0 Participants n=193 Participants	0 Participants n=395 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From the date of randomization to PSA progression median follow-up time is 6.47 months for enzalutamide and 2.99 months for placebo

Population: ITT population with available data.

Outcome measures

Outcome measures
Measure	Enzalutamide n=198 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=190 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Time to Prostate-specific Antigen (PSA) Progression	8.31 Months Interval 5.72 to 10.25	2.86 Months Interval 2.83 to 4.63	—	—

SECONDARY outcome

Timeframe: From the date of randomization to deaths from any cause median follow-up time is 42.32 months for enzalutamide and 26.81 months for placebo

Population: ITT population

Duration of overall survival was defined as the time from the randomization to deaths from any cause. For participants who were alive at the time of the data analysis, overall survival time was censored to the last know date the participants were known to be alive.

Outcome measures

Outcome measures
Measure	Enzalutamide n=202 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=193 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Duration of Overall Survival	39.06 Months Interval 29.24 to 57.63	27.10 Months Interval 21.88 to 37.82	—	—

SECONDARY outcome

Timeframe: From the date of randomization to the rPFS event (deaths from any cause and radiographic disease progression) median follow-up time is 5.55 months for enzalutamide and 3.71 months for placebo

Population: ITT population with available data.

Duration of Radiographic Progression-free Survival (rPFS) was defined as the time from randomization to the rPFS event (deaths from any cause and radiographic disease progression). Radiographic disease progression is defined by RECIST 1.1 for soft tissue disease, or PCWG2 for bone lesions. If a participant met the criteria for more than 1 censoring rule, they were censored with the earliest censoring date. The radiographic progression date was the first date when progression definition was met, not confirmed.

Outcome measures

Outcome measures
Measure	Enzalutamide n=198 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=190 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment	NA Months Interval 10.97 to Could not be estimated due to the low number of events	5.29 Months Interval 3.61 to 11.33	—	—

SECONDARY outcome

Timeframe: From the date of randomization to the first skeletal-related event median follow-up time is 7.39 months for enzalutamide and 5.29 months for placebo

Population: ITT population with available data.

Time to first skeletal-related event (SRE) was defined as the time from randomization to the first skeletal-related event, defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of anti-neoplastic therapy to treat bone pain. Participants who have not had a SRE at the time of the analysis were censored at their last assessment indicating no evidence of SRE.

Outcome measures

Outcome measures
Measure	Enzalutamide n=198 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=190 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Time to First Skeletal-Related Event	NA Months Could not be estimated due to the low number of events	NA Months Could not be estimated due to the low number of events	—	—

SECONDARY outcome

Timeframe: From the date of randomization to initiation of cytotoxic chemotherapy median follow-up time is 7.39 months for enzalutamide and 5.19 months for placebo

Population: ITT population with available data.

Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to initiation of cytotoxic chemotherapy. It included only therapies for prostate cancer. When multiple cytotoxic chemotherapies were initiated, the first chemotherapy was used to determine the time to event. Participants who did not start cytotoxic chemotherapy at the time of analysis data cutoff were censored at the date of their last assessment indicating no evidence of cytotoxic chemotherapy usage.

Outcome measures

Outcome measures
Measure	Enzalutamide n=198 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=190 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Time to Initiation of Cytotoxic Chemotherapy	NA Months Could not be estimated due to the low number of events	13.93 Months Could not be estimated due to the low number of events	—	—

SECONDARY outcome

Timeframe: From baseline to the lowest post-baseline PSA result median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo

Population: ITT population with available data.

Best PSA response was defined as as ≥50% reductions in PSA level from baseline to the lowest post-baseline PSA result as determined by the central laboratory, with a consecutive assessment conducted at least 3 weeks later to confirm the PSA response. Only participants who had both baseline and post-baseline assessments were included in the analysis.

Outcome measures

Outcome measures
Measure	Enzalutamide n=182 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=148 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)	120 Participants	15 Participants	—	—

SECONDARY outcome

Timeframe: From the date of randomization median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo

Population: ITT population with available data.

Participants with measurable soft tissue disease at screening visit (i.e., at least one target lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) who have an objective response (complete response (CR) or partial response (PR)) during the study were included in the best overall soft tissue response assessment. The best overall soft tissue response was based on the investigator assessment using RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.

Outcome measures

Outcome measures
Measure	Enzalutamide n=65 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=60 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Best Overall Soft Tissue Response	18 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85

Outcome measures

Outcome measures
Measure	Enzalutamide n=12 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=12 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=12 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=12 Participants Active metabolite
Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 1	0.975 hour Interval 0.5 to 6.05	24.0 hour Interval 0.55 to 24.9	24.0 hour Interval 0.55 to 24.9	0.975 hour Interval 0.5 to 24.0
Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 85	1.00 hour Interval 0.0 to 2.0	1.02 hour Interval 0.217 to 24.1	0 hour Interval 0.0 to 23.8	0.250 hour Interval 0.0 to 23.8

SECONDARY outcome

Timeframe: From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85

Outcome measures

Outcome measures
Measure	Enzalutamide n=12 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=12 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=12 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=12 Participants Active metabolite
Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 1	3.92 micrograms/milliliter (μg/mL) Standard Deviation 1.37	0.112 micrograms/milliliter (μg/mL) Standard Deviation 0.0794	0.175 micrograms/milliliter (μg/mL) Standard Deviation 0.0921	3.94 micrograms/milliliter (μg/mL) Standard Deviation 1.34
Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 85	20.0 micrograms/milliliter (μg/mL) Standard Deviation 3.22	14.0 micrograms/milliliter (μg/mL) Standard Deviation 23.5	15.2 micrograms/milliliter (μg/mL) Standard Deviation 3.44	34.2 micrograms/milliliter (μg/mL) Standard Deviation 4.98

SECONDARY outcome

Timeframe: From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85

Population: The Pharmacokinetic Analysis Set (PKAS) population consisted of all participants who received at least 1 dose of study drug and who provided blood samples for drug concentrations at at least 1 time point. Number of participants analyzed is the number of participants with available data at this time point.

Outcome measures

Outcome measures
Measure	Enzalutamide n=12 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=12 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=12 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=12 Participants Active metabolite
AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2	43.1 μg*h/mL Standard Deviation 9.64	1.81 μg*h/mL Standard Deviation 0.972	2.17 μg*h/mL Standard Deviation 1.30	45.3 μg*h/mL Standard Deviation 10.1

SECONDARY outcome

Timeframe: From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85

N is the number of participants with available data at this time point.

Outcome measures

Outcome measures
Measure	Enzalutamide n=12 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=12 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=12 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=12 Participants Active metabolite
Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 1	1.65 μg/mL Standard Deviation 0.343	0.111 μg/mL Standard Deviation 0.0801	0.164 μg/mL Standard Deviation 0.0942	1.82 μg/mL Standard Deviation 0.363
Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 85	17.6 μg/mL Standard Deviation 3.09	6.09 μg/mL Standard Deviation 3.07	13.7 μg/mL Standard Deviation 2.91	31.2 μg/mL Standard Deviation 4.00

SECONDARY outcome

Timeframe: From the date of randomization up to Days 2, 3, 8, 22, 29, 43, 57, 85, 86, 113, 141 and 169

N is the number of participants with available data at this time point.

Outcome measures

Outcome measures
Measure	Enzalutamide n=12 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=12 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=12 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=12 Participants Active metabolite
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 29 predose	19.6 μg/mL Standard Deviation 4.00	8.16 μg/mL Standard Deviation 12.5	10.9 μg/mL Standard Deviation 3.72	30.5 μg/mL Standard Deviation 5.47
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 2 predose	1.65 μg/mL Standard Deviation 0.343	0.111 μg/mL Standard Deviation 0.0801	0.164 μg/mL Standard Deviation 0.0942	1.82 μg/mL Standard Deviation 0.363
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 3 predose	3.29 μg/mL Standard Deviation 1.16	0.302 μg/mL Standard Deviation 0.256	0.367 μg/mL Standard Deviation 0.188	3.66 μg/mL Standard Deviation 1.24
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 8 predose	9.39 μg/mL Standard Deviation 2.07	1.21 μg/mL Standard Deviation 0.923	1.94 μg/mL Standard Deviation 0.983	11.3 μg/mL Standard Deviation 2.62
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 22 predose	17.6 μg/mL Standard Deviation 2.37	6.09 μg/mL Standard Deviation 8.26	8.34 μg/mL Standard Deviation 2.74	25.9 μg/mL Standard Deviation 3.25
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 43 predose	17.0 μg/mL Standard Deviation 4.13	12.5 μg/mL Standard Deviation 22.1	14.0 μg/mL Standard Deviation 3.99	31.0 μg/mL Standard Deviation 5.82
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 57 predose	17.8 μg/mL Standard Deviation 3.09	18.4 μg/mL Standard Deviation 28.2	14.7 μg/mL Standard Deviation 3.88	32.5 μg/mL Standard Deviation 4.57
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 85 predose	17.9 μg/mL Standard Deviation 3.19	6.33 μg/mL Standard Deviation 2.95	14.9 μg/mL Standard Deviation 3.67	32.8 μg/mL Standard Deviation 5.10
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 86 predose	17.6 μg/mL Standard Deviation 3.09	6.09 μg/mL Standard Deviation 3.07	13.7 μg/mL Standard Deviation 2.91	31.2 μg/mL Standard Deviation 4.00
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 113 predose	17.5 μg/mL Standard Deviation 4.14	17.5 μg/mL Standard Deviation 33.1	15.0 μg/mL Standard Deviation 3.21	32.5 μg/mL Standard Deviation 3.72
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 141 predose	17.3 μg/mL Standard Deviation 3.73	5.52 μg/mL Standard Deviation 2.10	14.3 μg/mL Standard Deviation 3.90	31.6 μg/mL Standard Deviation 4.70
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Day 169 predose	17.2 μg/mL Standard Deviation 5.55	5.09 μg/mL Standard Deviation 2.27	14.0 μg/mL Standard Deviation 4.80	31.2 μg/mL Standard Deviation 5.02

SECONDARY outcome

Timeframe: From the date of randomization up to Multiple Dosing Day 85

Outcome measures

Outcome measures
Measure	Enzalutamide n=10 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=10 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=10 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=10 Participants Active metabolite
Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)	0.387 L/h Standard Error 0.0774	NA L/h Standard Error NA Metabolite dose was unknown.	NA L/h Standard Error NA Metabolite dose was unknown.	NA L/h Standard Error NA Metabolite dose was unknown.

SECONDARY outcome

Timeframe: From the date of randomization up to Multiple Dosing Day 85

Outcome measures

Outcome measures
Measure	Enzalutamide n=10 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=10 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=10 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=10 Participants Active metabolite
Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2	1.15 Ratio Standard Deviation 0.110	1.19 Ratio Standard Deviation 0.364	1.09 Ratio Standard Deviation 0.0897	1.08 Ratio Standard Deviation 0.0581

SECONDARY outcome

Timeframe: From the date of randomization up to Multiple Dosing Day 85

Outcome measures

Outcome measures
Measure	Enzalutamide n=10 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=10 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=10 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 n=10 Participants Active metabolite
AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2	427 μg*h/mL Standard Deviation 79.8	149 μg*h/mL Standard Deviation 74.1	308 μg*h/mL Standard Deviation 68.2	735 μg*h/mL Standard Deviation 109

SECONDARY outcome

Timeframe: From first dose on Day 1 until 28 days after the last dose of study drug, or one day before the date of initiation of cytotoxic chemotherapy or an investigational agent for treatment of prostate cancer, whichever comes first, up to 123 months and 24 days

Population: Safety Analysis Set consisted of all randomized participants who received at least 1 dose of study drug.

An AE was defined as any untoward medical occurrence, temporally associated with use of medicinal product, whether considered related to medicinal product. AE could therefore be any unfavorable \& unintended sign, symptom, or disease temporally associated with use of a medicinal product. An AE was considered serious if, results in death; is life-threatening; results in persistent disability; results in congenital anomaly; requires inpatient hospitalization; or leads to prolongation of hospitalization; other medically important events. TEAE was defined as AE occurring from time of study drug administration on Day 1 until follow-up visit (28 days after last dose, or one day before date of initiation of cytotoxic chemotherapy or an investigational agent, whichever comes first). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.

Outcome measures

Outcome measures
Measure	Enzalutamide n=202 Participants Participants received 160 mg of enzalutamide orally once a day during double blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 29.4 months). Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 54.3 months).	Placebo n=193 Participants Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer (up to 18.6 months).	M2- N-Desmethyl Enzalutamide n=51 Participants N-desmethyl enzalutamide (active metabolite)	Enzalutamide Plus M2 Active metabolite
Number of Participants With Adverse Events (AE) Treatment Emergent Adverse Events (TEAEs)	190 Participants	166 Participants	47 Participants	—
Number of Participants With Adverse Events (AE) Grade 3 or Higher TEAE	98 Participants	66 Participants	28 Participants	—
Number of Participants With Adverse Events (AE) TEAE Leading to Death	24 Participants	7 Participants	7 Participants	—
Number of Participants With Adverse Events (AE) Serious TEAE	87 Participants	57 Participants	24 Participants	—
Number of Participants With Adverse Events (AE) TEAE That Was Primary Reason for Treatment Discontinuation	32 Participants	33 Participants	7 Participants	—
Number of Participants With Adverse Events (AE) TEAE Leading to Study Drug Discontinuation	49 Participants	42 Participants	12 Participants	—
Number of Participants With Adverse Events (AE) TEAE Leading to Dose Reduction of Study Drug	4 Participants	3 Participants	2 Participants	—
Number of Participants With Adverse Events (AE) TEAE Leading to Dose Interruption of Study Drug	28 Participants	16 Participants	7 Participants	—
Number of Participants With Adverse Events (AE) TEAE Related to Study Drug	102 Participants	59 Participants	13 Participants	—
Number of Participants With Adverse Events (AE) Grade 3 or Higher TEAE Related to Study Drug	26 Participants	13 Participants	5 Participants	—
Number of Participants With Adverse Events (AE) Serious TEAE Related to Study Drug	14 Participants	7 Participants	3 Participants	—

Adverse Events

Enzalutamide

Serious events: 87 serious events

Other events: 169 other events

Deaths: 85 deaths

Placebo

Serious events: 57 serious events

Other events: 125 other events

Deaths: 57 deaths

Placebo Patients Crossover to Enzalutamide 160 mg

Serious events: 24 serious events

Other events: 31 other events

Deaths: 21 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosure

Astellas Pharma Inc

Phone: 8008887704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or 18 months after study completion date at all sites, whichever is first. Sponsor must receive a site's manuscript at least 45 days prior to publication for review and comment. If requested Sponsor may delay the publication for up to 60 days to seek patent protection.
Publication restrictions are in place

Restriction type: OTHER