Pharmacokinetics and Safety of Enzalutamide in Healthy Chinese Male Volunteers

Abstract Purpose This open-label, single-dose study evaluated the pharmacokinetic profiles of enzalutamide and its major metabolites and the safety of enzalutamide in healthy, Chinese male volunteers. Methods Fourteen volunteers (median age, 28.5 years) received a single oral dose of enzalutamide (160 mg) under fasting conditions on day 1 and were followed for 50 days. Pharmacokinetic profiles were obtained for enzalutamide and its major metabolites, carboxylic acid metabolite (M1; inactive metabolite) and N -desmethyl enzalutamide (M2; active metabolite), on day 1 up to 1176 hours (49 days). Safety data were also collected. Findings Enzalutamide plasma concentration rapidly increased (median T max , 1.5 hours) followed by a slow decrease (mean t ½ , 90.7 hours). M1 and M2 plasma concentrations increased gradually with a median T max of 72.0 and 121 hours, respectively. M1 and M2 mean metabolite-to-parent ratios were 0.2 and 1.3, respectively. Mean AUC 0–∞ of enzalutamide plus M2 was 828 μg h/mL versus 368 μg h/mL for enzalutamide alone. Mean t ½ , maximum concentration, and T max of enzalutamide plus M2 were comparable with those of enzalutamide. Drug-related treatment-emergent adverse events were reported in 4 men (28.6%): 1 each of upper respiratory tract infection, chest discomfort, increased blood bilirubin, and decreased white blood cell count. No deaths or serious treatment-emergent adverse events were observed. Implications The pharmacokinetic profiles of enzalutamide, M1, M2, and enzalutamide plus M2 in healthy Chinese men were generally consistent with those in white men. No new safety concerns were found. Chinese Clinical Trial Registration identifier: CTR20150635.