Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer

Inclusion Criteria:

   - Males age 18 or older;

   - Histologically or cytologically confirmed adenocarcinoma of the prostate;

   - Ongoing androgen deprivation therapy;

   - Serum testosterone level ≤ 50 ng/dL (1.73 nmol/L) at the Screening visit;

   - Progressive disease at study entry defined by prostate-specific antigen (PSA)
   progression and/or radiographic progression that occurred while the patient was on
   primary androgen deprivation therapy;

   - Asymptomatic or mildly symptomatic from prostate cancer;

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;

   - Estimated life expectancy of ≥ 12 months;

   - Able to swallow the study drug and comply with study requirements.

Exclusion Criteria:

   - Severe concurrent disease, infection, or co-morbidity;

   - Known or suspected brain metastasis or active leptomeningeal disease;

   - History of another invasive malignancy within the previous 5 years other than treated
   non-melanomatous skin cancer and American Joint Committee on Cancer (AJCC) Stage 0 or
   Stage 1 cancers that have a remote probability of recurrence;

   - Absolute neutrophil count < 1,500/µL, or platelet count < 100,000/µL, or hemoglobin <
   9 g/dL at the Screening visit;

   - Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >
   2.5 times the upper limit of normal (ULN) at the Screening visit;

   - Creatinine > 2 mg/dL at the Screening visit;

   - Albumin < 3.0 g/dL at the Screening visit;

   - History of seizure or any condition that may predispose to seizure;

   - Clinically significant cardiovascular disease;

   - Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer
   disease within last 3 months);

   - Major surgery within 4 weeks of enrollment;

   - Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment;

   - Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment;

   - Prior radiation or radionuclide therapy for treatment of distant metastases;

   - Prior ketoconazole, abiraterone, or cytotoxic chemotherapy for prostate cancer;

   - Treatment with hormonal therapy or biologic therapy for prostate cancer within 4 weeks
   of enrollment;

   - Use of antiandrogens within 4 weeks prior to enrollment;

   - Prior disease progression, as assessed by the Investigator, while receiving
   bicalutamide;

   - Participation in a previous clinical trial of enzalutamide or an investigational agent
   that inhibits the androgen receptor or androgen synthesis (patients who received
   placebo are acceptable);

   - Use of an investigational agent within 4 weeks of enrollment;

   - Use of herbal products that may have hormonal anti-prostate cancer activity and/or are
   known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids for
   prostate cancer within 4 weeks of enrollment;

   - Any condition or reason that, in the opinion of the Investigator, interferes with the
   ability of the patient to participate in the trial, which places the patient at undue
   risk, or complicates the interpretation of safety data.

Open-Label Treatment Period:

Inclusion Criteria:

   - Received randomized double blind treatment in MDV3100-09 as follows:

      - Randomized to enzalutamide and receiving enzalutamide at the time of study
      unblinding;

      - Randomized to bicalutamide and receiving bicalutamide at the time of study
      unblinding;

      - Randomized to bicalutamide and discontinued bicalutamide before study unblinding;

   - Willing to maintain androgen deprivation therapy with a gonadotropin releasing hormone
   (GnRH) agonist/antagonist or has had a bilateral orchiectomy.

Exclusion Criteria:

   - Is currently or has taken commercially available enzalutamide (Xtandi) prior to
   participation in this open-label extension;

   - Discontinued enzalutamide during the double-blind portion of the study prior to
   unblinding;

   - Has any clinically significant cardiovascular, dermatologic, endocrine,
   gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic,
   psychiatric, psychologic, pulmonary, or renal disorder or any other condition,
   including excessive alcohol or drug abuse, or secondary malignancy, that may interfere
   with study participation in the opinion of the investigator or medical monitor;

   - Has a current or previously treated brain metastasis or leptomeningeal disease;

   - Has a history of seizure or any condition that may predispose to seizure (eg, prior
   cortical stroke or significant brain trauma);

   - Has a history of loss of consciousness or transient ischemic attack within 12 months
   of open label day 1;

   - Has taken cytotoxic chemotherapy or investigational therapy within 4 weeks before
   enrollment (open label day 1).