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 (EGFR) tyrosine kinase inhibitor. This Phase I, open-label, two-period crossover study aimed to assess the impact of food on the pharmacokinetics (PK) of limertinib and its active metabolite, CCB4580030, in healthy Chinese volunteers (HVs). Volunteers were randomly assigned (1:1) to receive a single 160 mg dose of limertinib in a fasted state during period 1 and a fed state during period 2, or vice versa. A total of 24 HVs were enrolled, with 20 completing both study periods. PK samples were collected before dosing and up to 72 hours post-dose. PK parameters were analyzed using a noncompartmental method.
The results showed that limertinib was absorbed more quickly in the fasted state compared to the fed state. The geometric mean ratios (fed/fast) for maximum concentration (Cmax), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last), and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) for ASK120067 were 145.5%, 145.4%, and 141.9%, respectively. For CCB4580030, the geometric mean ratios of PK parameters were >125.00%, with 90% confidence intervals outside the predefined bioequivalence range.
The safety profiles were consistent across both prandial states, with limertinib being well tolerated. Food intake reduced the rate but increased the extent of limertinib absorption. Further investigation into the efficacy and safety of administering limertinib regardless of prandial state is needed.