- Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation, or signet cell or small cell features;
- Presence of bone metastatic disease as assessed by at least two lesions on whole body
metastable technetium-methylene diphosphonate (99mTc-MDP) bone scintigraphy;
- Throughout the study, ongoing androgen deprivation therapy with a luteinizing
hormone-releasing hormone (LHRH) analogue or prior bilateral orchiectomy (medical or
surgical castration);
- Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening;
- Progressive disease on androgen deprivation therapy at screening defined as a minimum
of two sequentially rising prostate-specific antigen (PSA) values (PSA1
PSA3);
- The screening PSA (PSA3) must be ≥ 2 μg/L (≥ 2 ng/mL).
- Prior enzalutamide, abiraterone acetate, aminoglutethimide, ketoconazole, radium Ra
223 dichloride or other bone-targeting radionuclides, or cytotoxic chemotherapy in the
CRPC setting for the treatment of prostate cancer or participation in a clinical trial
of an investigational agent that inhibits the androgen receptor or androgen synthesis
(unless treatment was placebo);
- Treatment with hormonal therapy (eg, androgen receptor inhibitors, 5-alpha reductase
inhibitors) or biologic therapy for prostate cancer (other than LHRH analogue therapy)
within 4 weeks before enrollment;
- Initiation of new treatment with denosumab, bisphosphonates, or systemic
corticosteroids for treatment of prostate cancer within 4 weeks before enrollment;
- Use of an investigational agent within 4 weeks before the screening visit;
- Radiation therapy to bone within 4 weeks before enrollment;
- Use of opiate analgesics for prostate cancer pain within 4 weeks before enrollment;
- Screening 99mTc-MDP bone scintigraphy showing a superscan;
- Visceral (eg, lung, liver) metastatic disease. Adenopathy is allowed;
- Current or previously treated brain metastasis or active leptomeningeal disease;
- History of seizure any time in the past for any reason or any condition that may
predispose to seizures.