Background: Etamicastat is a novel, potent, and reversible peripheral dopamineb-hydroxylase inhibitor that has been administered orally at doses up to 600 mg once daily for 10 days to male healthy volunteers and appears to be well tolerated. Objective: The aim of this study was to investigate the effect of food on the pharmacokinetics of etamicastat. Material and Methods: A single-center, open-label, randomized, two-way crossover study in 12 healthy male subjects was performed. Subjects were administered a single dose of etamicastat 200 mg following either a standard high-fat and high-calorie content meal (test) or 10 hours of fasting (reference). The statistical method for testing the effect of food on the pharmacokinetic parameters of interest was based upon the 90% confidence interval (CI) for the test/reference geometric mean ratio (GMR). The parameters of interest were maximum plasma concentration (C max), area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUC last), and AUC from time zero to infinity (AUC ¥). Bioequivalence was assumed when the 90% CI fell within the recommended acceptance interval (80, 125). Results: Etamicastat C max , AUC last , and AUC ¥ were 229 ng/mL, 1856 ng Á h/mL, and 2238 ng Á h/mL, respectively, following etamicastat in the fasting, and 166 ng/mL, 1737 ng Á h/mL, and 2119 ng Á h/mL, respectively, following etamicastat in the fed condition. Etamicastat test/reference GMR was 72.27% (90% CI 64.98, 80.38) for C max , 93.59% (90% CI 89.28, 98.11) for AUC last , and 96.47% (90% CI 91.67, 101.53) for AUC ¥. Time to C max was prolonged by the presence of food (p < 0.001). The C max , AUC last , and AUC ¥ values of the inactive metabolite BIA 5-961 were 275 ng/mL, 1827 ng Á h/mL, and 2009 ng Á h/mL, respectively, in the fasting, and 172 ng/mL, 1450 ng Á h/mL, and 1677 ng Á h/mL, respectively, in the fed condition. BIA 5-961 test/reference GMR was 62.42%