A Study to Evaluate the Effect of Multiple Doses of Enzalutamide on the Pharmacokinetics of Substrates of P-glycoprotein (Digoxin) and Breast Cancer Resistant Protein (Rosuvastatin) in Male Subjects With Prostate Cancer

Inclusion Criteria:

* Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
* Subject has a serum testosterone level \< 1.7 nmol/L (50 ng/dL) during the screening period if under androgen deprivation therapy (ADT).
* Subject has newly diagnosed metastatic prostate cancer or progressive disease on ADT confirmed by prostate-specific antigen (PSA) or imaging. Disease progression at screening is defined as 1 or more of the following 3 criteria:

  * PSA progression defined by a minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination. At least 1 PSA value within the 3 months leading up to the screening period should be ≥ 2μg/L (2 ng/mL).
  * Soft tissue disease progression defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 for soft tissue disease.
  * Bone disease progression defined by 2 or more new lesions on a bone scan.
* Subject is able to swallow enzalutamide capsules and comply with study requirements.
* Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
* Subject with a female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after final investigational product (IP) administration.
* Subject must not donate sperm during the treatment period and for 3 months after final IP administration.
* Subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after final IP administration.
* Subject has a body mass index range of 18.5 to 35.0 kg/m2 inclusive. The subject weighs at least 50 kg at screening.
* Subject has an estimated life expectancy of at least 6 months.
* Subject agrees not to participate in another interventional study while receiving IP treatment in the present study/participating in the present study.

Exclusion Criteria:

* Subject has any condition, which makes the subject unsuitable for study participation or is not likely to complete the study for any reason.
* Subject has known metastases in the liver or any hepatic disorder that could affect drug metabolism deemed clinically significant.
* Subject is self-reported as Asian.
* Subject has known or suspected brain metastasis or active leptomeningeal disease.
* Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation).
* Subject has a history of loss of consciousness or transient ischemic attack within 12 months of day 1.
* Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equine syndrome.
* Subject has clinically significant cardiovascular disease including the following:

  * Myocardial infarction within 6 months before screening
  * Unstable angina within 3 months before screening
  * New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure, unless a screening echocardiogram or multigated acquisition scan performed within 3 months before screening demonstrates a left ventricular ejection fraction ≥ 45%
  * History of clinically significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  * History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
  * Hypotension as indicated by systolic blood pressure \< 86 mm Hg at screening
  * Bradycardia as indicated by a heart rate of ≤ 45 beats per minute on the screening electrocardiogram (ECG)
  * Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mm Hg or diastolic blood pressure \> 105 mm Hg at screening
* Subject has previously received treatment with enzalutamide.
* Subject has undergone major surgery within 4 weeks prior to day 1.
* Subject has a known hypersensitivity reaction to enzalutamide, digoxin, rosuvastatin, contrast agents or any of the components of the formulations used.
* Subject has an absolute neutrophil count \< 1500/μL, platelet count \< 100000/μL and hemoglobin \< 6.2 mmol/L (9 g/dL) during the screening period.
* Subject has received any growth factors or blood transfusions within 7 days prior to the hematologic laboratory values obtained during the screening period.
* Subject has a total bilirubin (TBL) \> 1.5 times the upper limit of normal (ULN) (except for subjects with documented Gilbert's disease), alanine aminotransferase (ALT) \> 2.5 times the ULN or aspartate aminotransferase (AST) \> 2.5 times the ULN during the screening period. Subject with alkaline phosphatase (ALP) \> 3 times ULN will be excluded, unless deemed to be related to bone metastasis, rather than liver disease, and after discussion with the sponsor's medical monitor.
* Subject has an albumin \< 30 g/L (3.0 g/dL) or creatinine \> 177 μmol/L (\> 2 mg/dL) during the screening period.
* Subject has clinical signs and symptoms of hereditary or acquired coagulation disorders within 6 months prior to enrollment (day 1 visit).
* Subject has a history of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence. The medical monitor and investigator must agree that the possibility of recurrence is remote.
* Subject received treatment with chemotherapy within 4 weeks prior to enrollment (day 1) or plans to initiate treatment with chemotherapy during the study.
* Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 28 days or 5 half-lives, whichever is longer, prior to the initiation of screening.
* Subject has a gastrointestinal disorder affecting absorption.
* Subject uses concomitant medications that are inducers or inhibitors of P-gp and/or BCRP or strong CYP2C8 inhibitors or strong CYP3A4 inducers.
* Subject uses digoxin or rosuvastatin or concomitant medications that are contraindicated with digoxin or rosuvastatin.
* Subject has any history or evidence of any clinically significant gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease.
* Subject has used drugs of abuse (if not medically indicated) within 3 months prior to admission to the clinical unit.
* Subject has a history of consuming \> 21 units of alcohol per week within 3 months prior to day -1 (note: 1 unit = 10 g pure alcohol, 250 mL of beer \[5%\], 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) or the subject tests positive for alcohol at screening or on day -1.
* Subject has known active hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive, associated with positive anti-hepatitis B core and detectable hepatitis B virus DNA), active hepatitis C (hepatitis C virus \[HCV\] RNA \[qualitative\] is detected) or active viral hepatitis A (immunoglobulin M).
* Subject has a positive human immunodeficiency virus type 1 and/or type 2 at screening.
* Subject is an employee of Astellas, the study-related contract research organizations (CRO) or the clinical unit.