Effect of Food (Low and High Fat) on Pharmacokinetics of FCN-159, a Selective MEK Inhibitor, in Healthy Chinese Males.

Introduction: FCN-159 is a novel, oral, potent, selective MEK1/2 inhibitor in clinical development for the treatment of NRAS-mutant advanced melanoma and neurofibromatosis type 1. We investigated the effect of food on the pharmacokinetics (PK), safety, and tolerability of FCN-159. Methods: In this single-center, open-label, phase 1 study with a three-period, three-sequence, crossover design, healthy Chinese male subjects (n = 24) were randomized (1:1:1) to receive a single, oral 8 mg dose of FCN-159 in the fasted state (overnight, > 10 h), and with a low-fat and a high-fat meal, separated by a 10-day washout. PK parameters including time to maximum plasma concentration (C_max) and area under the concentration–time curve (AUC) were compared using geometric least-squares mean ratios (GLSMR), with the fasted state as the reference. A 90% CI for the GLSMR within 80–125% indicated no significant food effect. Results: A low-fat meal (n = 23) did not affect the PK profile of FCN-159: G LSMR for AUC from time 0 to t (AUC_0–t), 106.9% (90% CI 99.9–114.4%); AUC from time 0 to infinity (AUC_0–∞), 106.8% (90% CI 100.0–114.0%); C_max, 96.4% (90% CI 83.9–110.8%). A high-fat meal (n = 24) did not affect exposure to FCN-159 (GLSMR for AUC_0–t, 99.4%; 90% CI 99.0–106.3%; AUC_0–∞, 99.5 5%; 90% CI 93.2–106.1%), but modestly reduced C_max by 15% (GLSMR 84.9%; 90% CI 74.0–97.3%). Both the low-fat and high-fat meals slightly prolonged the median time to C_max by 0.5 h (90% CI 0.5–1.0 h). FCN-159 was generally well tolerated, with a lower incidence of treatment-emergent adverse events following administration in the fasted state than with a low-fat or high-fat meal (20.8%, 39.1%, and 37.5%, respectively). Conclusion: Food did not affect the PK profile of FCN-159 to a clinically meaningful extent compared with administration in the fasted state. [ABSTRACT FROM AUTHOR]