An Asian Study to Evaluate Efficacy and Safety of Oral En... | NCT02294461

ID	Type	Description	Link
CTR20140131	Registry Identifier	ChinaDrugTrials.org.cn

Label	Type	Description	Intervention Names
Enzalutamide	Experimental	Participants received 160 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. 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.	Drug: Enzalutamide
Placebo	Experimental	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.	Drug: Placebo
Placebo followed by Enzalutamide	Experimental	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.

Name	Type	Description	Arm Group Labels	Other Names
Enzalutamide	Drug	Oral	Enzalutamide Placebo followed by Enzalutamide

Measure	Description	Time Frame
Time to Prostate-specific Antigen (PSA) Progression	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.	From the date of randomization to PSA progression median follow-up time is 6.47 months for enzalutamide and 2.99 months for placebo

Measure	Description	Time Frame
Duration of Overall Survival	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.	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

Name	Affiliation	Role
Central Contact	Astellas Pharma Inc	Study Director

PubMed Identifier	Type	Citation	Retractions
35397772	Derived	Pu YS, Ahn H, Han W, Huang SP, Wu HC, Ma L, Yamada S, Suga K, Xie LP. Enzalutamide in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study. Adv Ther. 2022 Jun;39(6):2641-2656. doi: 10.1007/s12325-022-02140-2. Epub 2022 Apr 10.

Label	URL
Link to results and other applicable study documents on the Astellas Clinical Trials website.	View source

ID	Title	Description
FG000	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).

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Prostate-specific Antigen (PSA) Progression

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.

ITT population with available data.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	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).

Units	Counts
Participants	OG000198 OG001190

Title

Denominators

Categories

Title	Measurements
	OG0008.31(5.72 to 10.25) OG0012.86(2.83 to 4.63)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	P-value is based on an unstratified log-rank test. Hazard ratio calculated using unstratified Cox Proportional Hazards model with treatment as the only covariate for enzalutamide group versus placebo group.	Hazard Ratio		<0.0001		Unstratified Cox Proportional Hazards	0.38			2-Sided	95	0.27	0.52					Superiority or Other (legacy)

Secondary

Duration of Overall Survival

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.

ITT population

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	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).

Secondary

Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment

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.

ITT population with available data.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Enzalutamide	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).

Secondary

Time to First Skeletal-Related Event

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.

ITT population with available data.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Enzalutamide	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).

Secondary

Time to Initiation of Cytotoxic Chemotherapy

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.

ITT population with available data.

Posted

Median

95% Confidence Interval

Months

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

ID	Title	Description
OG000	Enzalutamide	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).

Secondary

Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)

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.

ITT population with available data.

Posted

Number

Participants

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001

Secondary

Best Overall Soft Tissue Response

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.

ITT population with available data.

Posted

Number

Participants

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

ID	Title	Description
OG000	Enzalutamide	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).

Secondary

Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2

Posted

Median

Full Range

hour

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite
OG002

Secondary

Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2

Posted

Mean

Standard Deviation

micrograms/milliliter (μg/mL)

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite

Secondary

AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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.

Posted

Mean

Standard Deviation

μg*h/mL

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite

Secondary

Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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

Posted

Mean

Standard Deviation

μg/mL

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite

Secondary

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

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

Posted

Mean

Standard Deviation

μg/mL

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

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite

Secondary

Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)

Posted

Mean

Standard Error

L/h

From the date of randomization up to Multiple Dosing Day 85

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite.

Secondary

Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2

Posted

Mean

Standard Deviation

Ratio

From the date of randomization up to Multiple Dosing Day 85

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite.
OG002

Secondary

AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2

Posted

Mean

Standard Deviation

μg*h/mL

From the date of randomization up to Multiple Dosing Day 85

ID	Title	Description
OG000	Enzalutamide	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).
OG001	M1- Carboxylic Acid Metabolite	Inactive metabolite

Secondary

Number of Participants With Adverse Events (AE)

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.

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

Posted

Number

Participants

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

ID	Title	Description
OG000	Enzalutamide	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). This arm represents both double blind and open-label period.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0006 events4 affected202 at risk EG0014 events4 affected193 at risk EG0021 events1 affected51 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Angina pectoris	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0012 events1 affected193 at risk EG0020 events0 affected51 at risk
Angina unstable	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cardiac arrest	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cardiac failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0005 events5 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Cardiac failure acute	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Myocardial infarction	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Angle closure glaucoma	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cataract	Eye disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0022 events2 affected51 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Constipation	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Functional gastrointestinal disorder	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Gastric mucosal lesion	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Nausea	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0022 events2 affected51 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0022 events2 affected51 at risk
Asthenia	General disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected202 at risk EG0013 events2 affected193 at risk EG0021 events1 affected51 at risk
Chest discomfort	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Death	General disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0013 events3 affected193 at risk EG0021 events1 affected51 at risk
Disease progression	General disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hernia	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Malaise	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Oedema peripheral	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Pyrexia	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cholangitis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Arthritis infective	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Bronchitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Cellulitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Chronic sinusitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Helicobacter infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Influenza	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Large intestine infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Pneumonia	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG00017 events16 affected202 at risk EG0010 events0 affected193 at risk EG0023 events3 affected51 at risk
Sepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Septic shock	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0011 events1 affected193 at risk EG0023 events2 affected51 at risk
Subcutaneous abscess	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0012 events2 affected193 at risk EG0020 events0 affected51 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Urosepsis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0023 events2 affected51 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Neutrophil count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Platelet count decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Prostatic specific antigen increased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Weight decreased	Investigations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0022 events1 affected51 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0013 events2 affected193 at risk EG0021 events1 affected51 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0004 events4 affected202 at risk EG0015 events3 affected193 at risk EG0021 events1 affected51 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0022 events2 affected51 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Malignant neoplasm of thorax	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Metastases to bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0012 events2 affected193 at risk EG0020 events0 affected51 at risk
Metastases to rectum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Schwannoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0013 events1 affected193 at risk EG0020 events0 affected51 at risk
Spinal cord neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Brain oedema	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Cerebral infarction	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Cerebral thrombosis	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Cerebrovascular insufficiency	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Cognitive disorder	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Dizziness	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected202 at risk EG0010 events0 affected193 at risk EG0022 events1 affected51 at risk
Hydrocephalus	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Hypoaesthesia	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Ischaemic stroke	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Loss of consciousness	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Myelopathy	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Nerve compression	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Spinal cord compression	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Syncope	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Organic brain syndrome	Psychiatric disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0006 events4 affected202 at risk EG0011 events1 affected193 at risk EG0021 events1 affected51 at risk
Azotaemia	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Calculus bladder	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Calculus urinary	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Dysuria	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0013 events2 affected193 at risk EG0020 events0 affected51 at risk
End stage renal disease	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Haematuria	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG00010 events8 affected202 at risk EG0016 events6 affected193 at risk EG0020 events0 affected51 at risk
Haemorrhage urinary tract	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected202 at risk EG0011 events1 affected193 at risk EG0022 events2 affected51 at risk
Renal failure	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Ureteric rupture	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Urethral stenosis	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Urinary bladder haemorrhage	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Urinary retention	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0007 events7 affected202 at risk EG0012 events2 affected193 at risk EG0021 events1 affected51 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Prostatic haemorrhage	Reproductive system and breast disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0012 events1 affected193 at risk EG0020 events0 affected51 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0012 events2 affected193 at risk EG0020 events0 affected51 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0022 events1 affected51 at risk
Bilateral orchidectomy	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Chemotherapy	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0014 events4 affected193 at risk EG0020 events0 affected51 at risk
Medical device change	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Nephrostomy tube removal	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Radiotherapy	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Spinal laminectomy	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Tumour excision	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Ureteral stent insertion	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0010 events0 affected193 at risk EG0021 events1 affected51 at risk
Ureteral stent removal	Surgical and medical procedures	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0004 events3 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hypertensive crisis	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Hypotension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected202 at risk EG0011 events1 affected193 at risk EG0020 events0 affected51 at risk
Malignant hypertension	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk
Venous thrombosis limb	Vascular disorders	MedDRA v23.0	Systematic Assessment	EG0002 events1 affected202 at risk EG0010 events0 affected193 at risk EG0020 events0 affected51 at risk

Facility	Status	City	State	ZIP	Country	Contacts
CN00103		Beijing			China
CN00104

ID	Term
D055534	Bulbo-Spinal Atrophy, X-Linked
D011471	Prostatic Neoplasms

ID	Term
D009134	Muscular Atrophy, Spinal
D013118	Spinal Cord Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D016472	Motor Neuron Disease
D009468	Neuromuscular Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Title	Description
BG000	Enzalutamide	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).
BG001	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). 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).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Enzalutamide	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).	85	202	87	202	169	202
EG001	Placebo	Participants received enzalutamide matching placebo orally once a day during DB 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).	57	193	57	193	125	193
EG002	Placebo Patients Crossover to Enzalutamide 160 mg	Eligible participants who received enzalutamide matching placebo during DB period and who provided consent to take part in OLP, 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).	21	51	24	51	31	51