A Study to Evaluate the Potential Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With Enzalutamide

Inclusion Criteria

• Subject has histologically confirmed metastatic adenocarcinoma of the prostate.
• Subject has ongoing androgen deprivation therapy with a Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) or bilateral orchiectomy (i.e., surgical or medical castration).
• Subject has disease progression by at least one of the following:
• Prostate-Specific Antigen (PSA) progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each draw;
• Bone disease progression as defined by Prostate Cancer Working Group 2 guidelines (at least 2 new lesions) on bone scan; or
• Soft tissue disease progression as defined by RECIST 1.1
• For subjects who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the study.
• Subject must have failed at least one course of androgen deprivation therapy (ADT), i.e., treatment with GnRH analogues.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Subject has been evaluated by a local neurologist prior to study entry who has determined the subject has at least one risk factor for seizure including:
• past history of seizure due to any cause except a single febrile seizure in childhood. Patients with a history of seizures should not have had a seizure within 12 months of Screening and must have had no anticonvulsants for 12 months prior to Screening,
• history of cerebrovascular accident (CVA) or transient ischemic attack (TIA),
• history of traumatic brain or head injury with loss of consciousness
• unexplained loss of consciousness within the last 12 months,
• presence of a space occupying lesion in the brain including previously treated brain metastasis(es) or primary central nervous system (CNS) tumor,
• history of arteriovenous malformations of the brain,
• history of brain infection (i.e., abscess, meningitis, or encephalitis),
• current use of medication that may lower seizure threshold
• presence of Alzheimer's disease, meningioma, leptomeningeal disease from prostate cancer.
• Subject is able to swallow the study drug and comply with study requirements.
• Subject agrees not to participate in another interventional study while on treatment.
• Male subject and his female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period and for 3 months after final study drug administration.
• Two acceptable forms of birth control include:
• Condom (barrier method of contraception), AND
• One of the following acceptable forms of contraception is required:
• Established use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository).
• Vasectomy or surgical castration at least 6 months prior to Screening.
• Male subject must use a condom, if having sex with a pregnant woman.
• Male subject must not donate sperm starting at Screening and throughout the study period and for at least 3 months after final drug administration.

Exclusion Criteria

• Subject with a history of exposure to enzalutamide.
• Subject has severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment.
• Subject is currently being treated with anti-epileptics.
• Subject has a history of seizure within the past 12 months of Screening as assessed by neurology examination and history.
• Subject with rapidly progressing visceral disease who has not received and is thought to be able to tolerate cytotoxic chemotherapy. (However, subject who has previously received cytotoxic chemotherapy is per