This is a single-center, single-dose, open-label, Phase I study to evaluate the mass balance, biotransformation, pharmacokinetic characteristics, excretion pathways, and safety of a single oral 200 mg/5 µCi dose of \[14C\]Zorifertinib in healthy Chinese adult male participants. The study includes a screening period (Day -14 to Day -1) and a dosing and observation period (Day 1 to Day 14). Blood, urine, and feces samples will be collected to measure radioactivity, drug concentrations, and metabolites. Safety will be assessed by adverse events, vital signs, laboratory tests, 12-lead ECG, and ophthalmic examinations. The target total radioactivity recovery is ≥90% of the administered dose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
Single oral administration of 200 mg/5 µCi \[¹⁴C\]Zorifertinib in healthy male subjects under fasting condition
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
Total radioactive recovery and cumulative total radioactive recovery in urine and feces at each time interval
Time frame: Pre-dose up to 312 hours after dosing, or until termination criteria met
Percentage of total radioactivity exposure (%AUC), percentage of parent drug and its metabolites (%Dose), and metabolite identification
Percentage of total radioactivity exposure (%AUC) accounted for by parent drug and its metabolites in plasma. Percentage of administered dose (%Dose) accounted for by parent drug and its metabolites in urine and faeces. Identification of metabolites in plasma, urine, and feces
Time frame: Pre-dose up to 312 hours after dosing, or until termination criteria met
Peak Plasma Concentration (Cmax)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Time to Peak Concentration (Tmax)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Area under the plasma concentration versus time curve (AUC)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Elimination Half-Life (t1/2)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Terminal Rate Constant (λz)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Apparent Volume of Distribution (Vz/F)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Apparent Clearance (CLz/F)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Mean Residence Time (MRT)
Pharmacokinetic parameters of total radioactivity in plasma and whole blood (if applicable)
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Whole blood / plasma total radioactivity ratio
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Peak Plasma Concentration (Cmax)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Time to Peak Concentration (Tmax)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Area under the plasma concentration versus time curve (AUC)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Elimination Half-Life (t1/2)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Terminal Rate Constant (λz)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Apparent Volume of Distribution (Vz/F)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Apparent Clearance (CLz/F)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
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Mean Residence Time (MRT)
Pharmacokinetic parameters for zorifertinib, its metabolite (AZ'1168), and other major metabolites (if applicable) in plasma
Time frame: Pre-dose up to 120 hours after dosing,or until termination criteria met
Incidence and severity of Adverse Events (AEs)
All adverse events were classified according to the CTCAE (version: 6.0)
Time frame: Pre-dose up to 312 hours after dosing, or until termination criteria met