Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation, signet cell, or small cell features;

- Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH)
agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);

- Testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening;

- Progressive disease on androgen deprivation therapy at enrollment;

- PSA and the screening PSA assessed by the central laboratory (central PSA) should be ≥
2 µg/L (2 ng/mL:

- PSA doubling time ≤ 10 months;

- No prior or present evidence of metastatic disease;

- Asymptomatic prostate cancer;

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

- Estimated life expectancy ≥ 12 months.

Exclusion Criteria:

- Prior cytotoxic chemotherapy;

- Use of hormonal therapy or biologic therapy for prostate cancer (other than approved
bone targeting agents and GnRH agonist/antagonist therapy) or use of an
investigational agent within 4 weeks of randomization;

- Known or suspected brain metastasis or active leptomeningeal disease;

- History of another invasive cancer within 3 years of randomization;

- Absolute neutrophil count < 1000/μL, platelet count < 100,000/μL, or hemoglobin < 10
g/dL (6.2 mmol/L) at screening;

- Total bilirubin ≥ 1.5 times the upper limit of normal;

- Creatinine > 2 mg/dL (177 µmol/L) at screening;

- Albumin < 3.0 g/dL (30 g/L) at screening;

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

- Clinically significant cardiovascular disease;

- Gastrointestinal disorder affecting absorption;

- Major surgery within 4 weeks of randomization;

- Hypersensitivity reaction to the active pharmaceutical ingredient or any of the
capsule components, including Labrasol, butylated hydroxyanisole, and butylated
hydroxytoluene;

- Any concurrent disease, infection, or comorbid condition that interferes with the
ability of the patient to participate in the trial, which places the patient at undue
risk, or complicates the interpretation of data, in the opinion of the investigator or
medical monitor.