Effect of Food on the Pharmacokinetics of Limertinib (ASK120067) and its Main Metabolite in Healthy Chinese Volunteers

Limertinib (ASK120067) is a newly developed third-generation epidermal growth factor receptor tyrosine kinase inhibitor. This phase I, open-label, 2-period crossover study was conducted to evaluate the effect of food on the pharmacokinetics (PK) of limertinib and its active metabolite CCB4580030 in Chinese healthy volunteers (HVs). HVs were randomly assigned (1:1) to receive a single dose of limertinib (160 mg) under the fasted state in period 1 and fed condition in period 2, or vice versa. Twenty-four HVs were enrolled, and 20 HVs completed both study periods. PK were assessed before dosing and ≤72 hours after dosing. PK parameters were analyzed by a noncompartmental method. Limertinib was absorbed faster in the fasted state compared with the fed state. The geometric mean ratios (fed/fast) of maximum concentration, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity for ASK120067 were 145.5%, 145.4%, and 141.9%, respectively. Geometric mean ratios of the PK parameters of CCB4580030 were >125.00% and 90% confidence intervals were outside the preset bioequivalent range. Safety profiles were similar in both prandial states, and limertinib was well tolerated. Food reduced the rate and increased the extent of limertinib absorption following oral administration. Whether limertinib can be administered regardless of prandial state in patients warrants further investigation of efficacy and safety.