A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate without neuroendocrine
differentiation or small cell features

- Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone
(LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of
randomization or bilateral orchiectomy (i.e., surgical or medical castration)

- Metastatic disease documented by one of the following:

- At least two bone lesions on bone scan, or

- Soft tissue disease documented by computed tomography (CT)/ magnetic resonance
imaging (MRI), or

- Unequivocal pelvic adenopathy short axis >2.0 cm in diameter by computed
tomography (CT)/ magnetic resonance imaging (MRI)

- Progressive disease at study entry defined as one or more of the following three
criteria occurring in the setting of castrate levels of testosterone:

- Prostate Specific Antigen (PSA) progression defined by a minimum of three rising
PSA levels with an interval of ≥ 1 week between each determination. The PSA
value should be ≥ 2 µg/L (2 ng/mL);

- Soft tissue disease progression defined by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1;

- Bone disease progression defined by two or more new lesions on bone scan

- Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief
Pain Inventory-Short Form (BPI-SF) Question #3 must be < 4); no use of opiate
analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior
to randomization

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including
subjects with decreased performance status not attributed to progressive and
symptomatic prostate cancer

- Estimated life expectancy of ≥ 12 months

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

Exclusion Criteria:

- Prior cytotoxic chemotherapy for prostate cancer

- Severe concurrent disease, infection, or comorbidity that would make the subject
inappropriate for enrollment

- Known or suspected brain and/or skull metastasis or active epidural disease

- History of another malignancy within the previous 5 years other than curatively
treated non-melanomatous skin cancer

- Current or prior treatment with estrogens and/or drugs with anti-androgenic
properties such as spironolactone > 50 mg/kg, or progestational agents for the
treatment of prostate cancer within 6 months prior to randomization

- Current or prior use of ketoconazole for the treatment of prostate cancer

- Use of antiandrogens within 6 weeks prior to randomization

- Documented prior disease progression while receiving antiandrogens. Disease
progression defined as PSA progression, radiographic progression and/or clinical
deterioration.

- Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within
6 months prior to randomization

- Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within
3 months prior to randomization or expectation of their use during the study

- Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to
randomization

- Major surgery within 2 months prior to randomization

- History of seizure including febrile seizure or any condition that may predispose to
seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss
of consciousness requiring hospitalization). Also, current or prior treatment with
anti-epileptic medications for the treatment of seizures or history of loss of
consciousness or transient ischemic attack within 12 months prior to randomization

- Clinically significant cardiovascular disease including myocardial infarction within
past six months or uncontrolled angina within past three months