18 Years and up
Accepting Healthy Volunteers?
- Subject is considered an adult according to local regulation at the time of signing
- Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of
the prostate without neuroendocrine differentiation, signet cell or small cell
- Subject has metastatic prostate cancer documented by positive bone scan (for bone
disease) or metastatic lesions on computed tomography (CT) or magnetic resonance
imaging (MRI) scan (for soft tissue). Subjects whose disease spread is limited to
regional pelvic lymph nodes are not eligible.
- Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist
during study treatment or have a history of bilateral orchiectomy (i.e., medical or
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Inclusion Criteria for Open-Label Extension:
- Subject received randomized double-blind treatment in ARCHES
- Subject has not met any of the discontinuation criteria in the main ARCHES protocol
- Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a
- Subject is able to swallow enzalutamide capsules whole and to comply with study
requirements throughout the study
- Subject and subject's female partner agree to follow contraception and sperm donation
requirements in main protocol
- Subject has received any prior pharmacotherapy, radiation therapy or surgery for
metastatic prostate cancer (the following exceptions are permitted):
- Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or
without concurrent antiandrogens prior to day 1, with no radiographic evidence of
disease progression or rising PSA levels prior to day 1;
- Subject may have 1 course of palliative radiation or surgical therapy to treat
symptoms resulting from metastatic disease if it was administered at least 4
weeks prior to day 1;
- Up to 6 cycles of docetaxel therapy with final treatment administration completed
within 2 months of day 1 and no evidence of disease progression during or after
the completion of docetaxel therapy;
- Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or
without concurrent antiandrogens prior to day 1 if subject was treated with
docetaxel, with no radiographic evidence of disease progression or rising PSA
levels prior to day 1;
- Prior ADT given for < 39 months in duration and > 9 months before randomization
as neoadjuvant/adjuvant therapy.
- Subject had a major surgery within 4 weeks prior to day 1.
- Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride)
within 4 weeks prior to day 1.
- Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4
weeks prior to day 1.
- Subject received treatment with systemic glucocorticoids greater than the equivalent
of 10 mg per day of prednisone within 4 weeks prior to day 1, intended for the
treatment of prostate cancer.
- Subject received treatment with herbal medications that have known hormonal
antiprostate cancer activity and/or are known to decrease PSA levels within 4 weeks
prior to day 1.
- Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or
enzalutamide for the treatment of prostate cancer or participation in a clinical study
of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700,
- Subject has known or suspected brain metastasis or active leptomeningeal disease.
- Subject has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or
hemoglobin < 10 g/dL (6.2 mmol/L).
- Subject has total bilirubin (TBL) ≥ 1.5 x the upper limit of normal (ULN) (except
subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) ≥ 2.5 x the ULN .
- Subject has creatinine > 2 mg/dL (177 μmol/L).
- Subject has albumin < 3.0 g/dL (30 g/L).
- Subject has a history of seizure or any condition that may predispose to seizure.
- Subject has history of loss of consciousness or transient ischemic attack within 12
months prior to day 1.
- Subject has clinically significant cardiovascular disease.
- Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless
administered at stable dose or to treat diagnosed osteoporosis
Exclusion Criteria for Open-Label Extension:
- Subject has taken commercially available enzalutamide (Xtandi).
- Subject's disease has progressed radiographically during the double-blind period of
the study and treatment with study drug was stopped prior to study-wide unblinding.
(Note: Subjects who progressed radiographically while in the double-blind portion of
the study and continued treatment per protocol are allowed to participate in the open
- After study-wide unblinding, subject has started any new investigational agent or
anti-neoplastic therapy intended to treat prostate cancer
- Subject has any clinically significant disorder or condition including excessive
alcohol or drug abuse, or secondary malignancy, which may interfere with study
- Subject has current or previously treated brain metastasis or active leptomeningeal
- Subject has a history of seizure or any condition that may increase the risk of