Effect of CYP3A4 inhibitor and induction on the pharmacokinetics and safety of FHND9041, a novel EGFR T790M inhibitor, in healthy Chinese

Table 2 Summary of FHND9041 PK parameters in healthy subjects after single oral administration of FHND9041 capsules at different stages (Itraconazole + FHND9041 group, PKPS)

Phase(n)	Descriptive statisticians	C_max (ng/mL)	T_max (h)	AUC_{0 − last} (ng·h/mL)	T_last (h)	AUC_{0 − inf} (ng·h/mL)	C_L/F (L/h)	V_z/F (L)	t_1/2 (h)
Monotherapy Phase(n = 15)	n	15	15	14^a	14^a	14^a	14^a	14^a	14^a
Monotherapy Phase(n = 15)	n	27.5 ± 8.78(32.0%)	4.00 (2.00, 12.00)	1732 ± 567 (32.7%)	239.33 (168.00,239.3)	1896 ± 619 (32.7%)	23.2 ± 7.08 (30.6%)	1911 ± 476 (24.9%)	59.2 ± 12.1 (20.5%)
Co-administration phase(n = 14^a)	n	13^b 31.3 ± 8.1 9 (26.2%)	13^b 8.00 (4.00, 23.55)	13^b 2850 ± 732 (25.7%)	13^b 336.00 (239.33,336.0)	13^b 3090 ± 828 (26.8%)	13^b 13.7 ± 3.28 (23.9%)	13^b 1738 ± 385 (22.2%)	13^b 89.5 ± 15.1 (16.9%)

Note: a: Subject RD004 withdrew informed consent during the monotherapy phase and terminated the trial early, without proceeding to the co-administration phase. PK samples were collected only from pre-dose to 96 h post-dose during the monotherapy phase, which may underestimate AUC0-last and Tlast. These parameters were not included in the descriptive statistics. Additionally, since AUC_{_%Extrap} > 20%, λ_z and other parameters calculated based on λ_z (e.g., AUC_{0 − inf}, CL/F, V_z/F, t_1/2, etc.) could not be accurately calculated and were also excluded from the descriptive statistics
b: Subject RD010 had a pre-dose concentration of FHND9041 exceeding 5% of Cmax during the co-administration phase with Itraconazole. PK parameters for this subject during this phase were excluded from the descriptive statistics

ISSN: 2050-6511