This is a single-center, randomized, open lebal, single-dose, three-period, crossover clinical study in healthy Chinese male subjects to assess the pharmacokinetics and bioequivalence/bioavailability of two formulation savolitinib tablets.
Thirty six Chinese male subjects who met the inclusion criteria but not met the exclusion criteria, will be hospitalized in Phase I Ward one day before first dosing and randomized into three groups, 12 subjects each, at a ratio of 1:1:1. The subjects in the different group will follow the fixed dosing regimen with 600 mg savolitinib tablets (200 mg/tablet x 3 tablets) after the standard meal on day 1 in cycle 1, 2 and 3 respectively: TRR, RTR or RRT, where "T" indicates dry granulation savolitinib tablet and "R" indicates wet granulation savolitinib tablet. PK blood samples, 2 mL each time, will be collected at the following time points in each dosing cycle: within 0.5 hours before dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24, 36, 48 hours after dosing(16 time-points).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Test preparation (T): dry granulation savolitinib tablets.
Reference preparation (R): wet granulation savolitinib tablets.
Shanghai Xuhui District Central Hospital
Shanghai, Shanghai Municipality, China
The area under the curve(AUC) of savolitinib
The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Maximum observed plasma concentration (Cmax) of savolitinib
Maximum observed concentration, occurring at Tmax.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
The time to Cmax (peak time, Tmax) of savolitinib
The time at which maximum plasma concentration (Cmax) is observed.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Half-life (t1/2) of savolitinib
The time required for the concentration of the drug to reach half of its original value.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
Bioequivalence of savolitinib
A term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.
To observe the safety of healthy volunteers after a single oral dose of savolitinib
Incidence of adverse events evaluated by NCI CTCAE v4.03
Time frame: From the first dose to within 12 days after the last dose
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Relative bioavailability of savolitinib
The area under the curve (AUC) is the definite integral in a plot of drug concentration in blood plasma vs. time.
Time frame: Measured on the Cycle1 Day1 to Day3, Cycle2 Day1 to Day3, Cycle3 Day1 to Day3, each cycle is 10 days.