This is an open-label, fixed-sequence Phase I clinical study that evaluates the effect of multiple doses of aumolertinib on the pharmacokinetics of midazolam (CYP 3A4 probe substrate) in sensitive EGFR (Epidermal Growth Factor Receptor) mutation-harboring patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
This is an open-label, fixed-sequence Phase I clinical study that evaluates the effect of multiple doses of aumolertinib on the pharmacokinetics of midazolam (CYP 3A4 probe substrate) in sensitive EGFR (Epidermal Growth Factor Receptor) mutation-harboring patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The study includes D1 (Day 1)-D2 (Day 2) of run-in period, C1D1 (Cycle 1 Day 1)-C1D21 (Cycle 1 Day 21) and C2D1 (Cycle 2 Day 1)-C2D2 (Cycle 2 Day 2). The enrolled subjects will receive a single oral dose of midazolam 2 mg (2 mg/mL, 1 mL) on D1 of the run-in period and on C2D1; and receive oral dose of aumolertinib 110 mg (55 mg/tablet, 2 tablets) once daily from C1D1 to C2D2.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Midazolam : The enrolled subjects will receive a single oral dose of Midazolam 2 mg (2 mg/mL, 1 mL) on D1 of the run-in period and on C2D1. Aumolertinib : Starting from C1D1, the enrolled subjects will receive oral dose of aumolertinib 110 mg (55 mg/tablet, 2 tablets) once daily until the criteria for terminating treatment are met.
Ethics Committee of the First Addiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGCmax, of midazolam and 1-hydroxymidazolam (midazolam combined with aumolertinib/midazolam administrated alone)
Maximum plasma concentration
Time frame: Day 1
AUC0-t of midazolam and 1-hydroxymidazolam (midazolam combined with aumolertinib/midazolam administrated alone)
Area under the plasma concentration-time curve from 0-t
Time frame: Day 1
AUC0-∞ of midazolam and 1-hydroxymidazolam (midazolam combined with aumolertinib/midazolam administrated alone)
Area under the plasma concentration-time curve from 0-∞
Time frame: Day 1
Cmin of aumolertinib, HAS-719 and other major metabolites (if applicable)
Minimum plasma concentration
Time frame: Day 1
Cmax of aumolertinib, HAS-719 and other major metabolites (if applicable)
Maximum plasma concentration
Time frame: Day 1
AUC0-24h of aumolertinib, HAS-719 and other major metabolites (if applicable)
Area under the plasma concentration-time curve from 0-24h
Time frame: Day 1
Tmax of aumolertinib, HAS-719 and other major metabolites (if applicable)
Time to reach Cmax
Time frame: Day 1
Incidence and severity of adverse event
Time frame: D25
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