Table 1.

Overview of clinical studies and studies of enzalutamide in healthy volunteers

Study	Population	Key eligibility criteria	Dosea and food intake
Dose escalation	140 patients with mCRPC	Progressive castration-resistant prostate cancer [5] and ECOG performance status grade of 0–1 (2 was allowed if due to bone pain)	Dose escalation: enzalutamide 30, 60, 150, 240, 360, 480 (as 240 mg bid), and 600 (as 300 mg bid) mg qd; for the single dose, drug was taken in the clinic with breakfast (patient could provide his own breakfast), and for the multiple-dose period, food intake was not controlled
Mass balance and biotransformation	6 healthy males	Healthy subjects, aged 18–55 years, BMI ≥18.5 and ≤30.0 kg/m2 inclusive	14C-enzalutamide 160 mg (100 µCi) single dose under fasting conditionsb
Food effect	60 healthy males under fed (n = 30) or fasted (n = 30) conditions	Healthy subjects, aged 18–55 years, body weight >50 kg, BMI 18–30 kg/m2 inclusive	Enzalutamide 160 mg single dose under fastedb or fed conditions (high-fat, high-calorie meal)
Hepatic impairment	28 males: 6 with mild hepatic impairment, 8 with moderate hepatic impairment, and 14 with normal hepatic functionc	Aged 18–69 years, BMI ≥18.5 and ≤34.0 kg/m2 inclusive; criteria for mild and moderate hepatic impairment were based on Child–Pugh classification [9]	Enzalutamide 160 mg single dose under fasting conditionsb
Phase III efficacy and safety (AFFIRM)	1199 patients with mCRPC (randomized 2:1 active-to-placebo)	Progressive castration-resistant prostate cancer [2] previously treated with one or two prior chemotherapy regimens, at least one of which was docetaxel-based. ECOG performance status grade of 0–2	Enzalutamide 160 mg qd; food intake was not controlled

bid twice daily, BMI body mass index, ECOG Eastern Cooperative Oncology Group, mCRPC metastatic castration-resistant prostate cancer, qd once daily

^aAll clinical trials used the same drug product presentation as the commercial product (Xtandi^®): a liquid-filled capsule of enzalutamide fully dissolved in caprylocaproyl polyoxylglycerides

^bNo caloric intake for at least 10 h predose and 4 h postdose

^cA total of 32 subjects were evaluated for pharmacokinetics in this study; however, the pharmacokinetic comparisons were based on 28 subjects due to the exclusion of four subjects (i.e. two pairs of subjects) in the mild hepatic impairment arms because of a >15 % difference in BMI between the matched pairs