A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC

This is a randomized (study medication assigned to participants by chance), double-blind
(neither the researchers nor the participants know what treatment the participant is
receiving), placebo-controlled, multinational, multicenter study of apalutamide in
participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days
before randomization), Treatment Phase (28 day treatment cycles until disease progression or
the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until
30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event
of a positive study result and notification of unblinding at either of the interim analyses
or at the final analysis, participants in the treatment Phase will have the opportunity to
enroll in an Open-label Extension Phase, which will allow participants to receive active drug
(apalutamide) for approximately 3 years. The radiographic progression-free survival or
overall survival will be evaluated. Participants' safety will be monitored throughout the
study.

Inclusion Criteria:

- Diagnosis of prostate adenocarcinoma as confirmed by the investigator

- Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc
bone scan. Participants with a single bone lesion must have confirmation of bone
metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1

- Participants who received docetaxel treatment must meet the following criteria: a)
Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last
dose of docetaxel <=2 months prior to randomization; c) Maintained a response to
docetaxel of stable disease or better, by investigator assessment of imaging and PSA,
prior to randomization

- Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or
surgical intervention; radiation therapy for metastatic lesions must be completed
prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to
randomization

- Allowed prior treatments for localized prostate cancer (all treatments must have been
completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other
forms of prior therapies including radiation therapy, prostatectomy,lymph node
dissection, and systemic therapies

Exclusion Criteria:

- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of
the prostate

- Known brain metastases

- Lymph nodes as only sites of metastases

- Visceral (ie, liver or lung) metastases as only sites of metastases

- Other prior malignancy less than or equal to 5 years prior to randomization with the
exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder
cancer

- Prior treatment with other next generation anti-androgens or other CYP17 inhibitors,
immunotherapy or radiopharmaceutical agents for prostate cancer

- History of seizures or medications known to lower seizure threshold