This is a single center,double-blind,randomized,parallel design, single and multiple dose trial to evaluate the pharmacokinetics(PK), safety and tolerability of ZSP1273,and the effect of food on ZSP1273 Pharmacokinetics.
The study will be divided in 3 parts : Study Part I(Single Ascending Dosing, SAD) will be a single ascending dose to be run at a maximum of 6 dose levels. Subjects included in this part of the study will receive only one dose level to limit the exposure to ZSP1273. Four subjects are planned to be included in the first group while 10 subjects are enrolled in every following cohort. Study Part II(Multiple Ascending Dosing, MAD) will start after completion of some Cohorts of Study Part I. Study Part II will be a multiple ascending dose to be run at a maximum of 3 dose levels. Subjects included in this part of the study will receive only one dose level. This part also enrolls 10 subjects in every cohort. Study Part III(Food Effect study, FE) will consists of 2 periods,and subjects will receive a single dose ranged from 100-600mg on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods.A total of 12 to 18 subjects will be included. All the 3 parts will be run in healthy subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
103
ZSP1273 tablet administered orally once daily under fasted condition
Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state.
ZSP1273 tablets administered orally once daily under fasted condition
The First Hospital of Jilin University
Changchun, Jilin, China
Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE)
Number of participants with TEAEs as assessed by CTCAE v5.0.
Time frame: At day 5, 9, 12 days post first dosing for SAD, MAD, FE part respectively
Tmax
The time after dosing when Cmax occurs (Tmax)
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
Cmax
Maximum concentration (Cmax)
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
t1/2z
t1/2z is defined as the time to decline half of the drug concentration in plasma.
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
AUCinf(AUC0-∞)
Area under the curve extrapolated until time is infinity (AUCinf)
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
AUClast(AUC0-t)
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
CL/F
CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F).
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
λz
λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
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Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition
ZSP1273 tablets administered orally once daily in the fasting state
Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state
ZSP1273 tablets administered orally once daily under fasted condition
Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition
ZSP1273 tablets administered orally once daily in the fasting state
Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition
ZSP1273 tablets administered orally once daily in the fasting state
Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state
ZSP1273 tablets administered orally once daily under fasted or fed condition
Participants will receive placebo matching to ZSP1273 orally once daily under fasted or fed condition
ZSP1273 tablets administered orally once daily under fasted or fed condition for 5 Days.
Participants will receive placebo matching to ZSP1273 orally once daily under fasted or fed condition for 5 Days.
ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.
Participants will receive placebo matching to ZSP1273 orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.
ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.
Participants will receive placebo matching to ZSP1273 orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
CLr
CLr is defined as how many milliliters of plasma in which some substance can be completely eliminated in the unit time (per minute) of two kidneys.
Time frame: UP to 5, 9, 12 days for SAD, MAD, FE part respectively
Food Effect PK Parameter: Fe0-t
Fe0-t is defined as the cumulative excretion rate of the drug in urine and feces.
Time frame: UP to 12 days
Food Effect PK Parameter: Ae
Ae is defined as the amount of unchanged drug excreted in urine or faeces after administration.
Time frame: UP to 12 days
Multiple-dose plasma PK parameter: Rac of ZSP1273 at steady state
Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1
Time frame: Up to 9 days
Multiple-dose plasma PK parameter: DF of ZSP1273 at steady state
DF is defined as the percentage of fluctuation in steady state is 100 \* (Cmax, ss - Cmin, ss)/Cavg, ss.
Time frame: Up to 9 days
Multiple-dose plasma PK parameter: Cmin of ZSP1273 at steady state
Cmin is defined as the minimum observed concentration of drug in plasma at steady state.
Time frame: Up to 9 days