A Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Patients With Metastatic Castration-Resistant Prostate Cancer

• Toxicity related to dosing after low-fat or high-fat meals [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
  Grade 3 or higher AEs of special interest, including fluid retention/edema, hypokalemia, cardiac disorders, hepatotoxicity (liver function test [LFT] abnormalities), and hypertension; or Grade 3 or higher serious adverse events (SAEs) that occur during the food safety evaluation period.
  
  
• Physical exams [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
  Grade 3 or higher AEs of fluid retention/edema, cardiac disorders, and hypertension
  
  
• Vital sign measurements [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
  Grade 3 or higher cardiac disorders, and hypertension
  
  
• Hematology and chemistry assessments [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
  Grade 3 or higher hypokalemia, hepatotoxicity (liver function test [LFT] abnormalities)
  
  

• Plasma levels of study agents [ Time Frame: Cycle 1 Day 7 through Cycle 1 Day 14 ] [ Designated as safety issue: No ]
  The metrics of abiraterone systemic exposure (Cmax and AUC) in the different prandial states
  
  

This is a multicenter, open-label study of 24 (up to a total of 28) men to assess the short-term safety of oral abiraterone acetate 1 g and oral prednisone 5 mg twice daily administered in the modified fasted state and after meals of various fat contents. All patients will take daily abiraterone acetate for the first 7 days in the modified fasted state (no food for 2 hours before and 1 hour after the dose). In Cohort 1, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized low-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14; or, in Cohort 2, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14. All patients will then continue to take abiraterone acetate daily in the modified fasted state starting on Cycle 1 Day 15 until disease progression. Toxicity related to dosing after the low-fat or high-fat meals is defined as Grade 3 or higher AEs of special interest; or Grade 3 or higher serious adverse events (SAEs) that occur during the food safety evaluation period. Cohort 2 may be expanded to a total of 18 evaluable patients if deemed to be safe. Decisions regarding the escalation of cohort or expansion of cohorts will be made by a study evaluation team. Pharmacokinetic evaluation for each cohort will be performed on Cycle 1 Days 7 and 14 at predose and multiple timepoints postdose over 24 hours; Cycle 1 Days 8 and 11 at 2 hours following abiraterone acetate dose administration. Abiraterone acetate, 1 g (four 250-mg tablets) orally (taken by mouth) once daily. Patients may take abiraterone acetate until progression of clinical disease. Prednisone, 5 mg, orally, twice a day.