This is a single-center, open-label, single-dose phase I study, the study is divided into two stages. The stage 1 is to investigate the absorption, metabolism and excretion of XZP-3621 tablets in healthy Chinese subjects. The stage 2 is to evaluate the effect of food on the Pharmacokinetics of single-dose XZP-3621 tablets in Chinese Healthy Volunteers. In addition, the safety of XZP-3621 tablets in Chinese Healthy Volunteers will also be evaluated.
Stage 1: 10 healthy adult subjects will be included in the study. Excretion (feces, urine) and vomit samples will be collected daily and tested for prototype drug and metabolites of XZP-3621, the metabolites will be identified in all substrates except vomits pose-dose of 400 mg XZP-3621 tablets. Vomit samples collection: Time interval for subject vomit collection (if any) (planned):0\~4 h,4\~8 h,8\~12 h,12\~24 h,24\~48 h,48\~72 h,72\~96 h,96\~120 h,120\~144 h,144\~168 h,168\~192 h after taking single XZP-3621 tablet. Samples of all vomits during that time interval will be collected at each time interval after taking single XZP-3621 tablet. Urine samples collection: Time interval for sample collection(planned):24h before taking single XZP-3621 tablet,0\~4 h,4\~8 h,8\~12 h,12\~24 h,24\~48 h,48\~72 h,72\~96 h,96\~120 h,120\~144 h,144\~168 h,168\~192 h after taking single XZP-3621 tablet, Urine samples were collected from each subject at a total of 12 time intervals (Only one urine sample should be collected within 24 hours before taking single XZP-3621 tablet), Urine volume was accurately recorded for each time period. Feces samples collection: Interval of fecal sample collection of subjects (planned):24h before taking single XZP-3621 tablet,0\~24 h,24\~48 h,48\~72 h,72\~96 h,96\~120 h,120\~144 h,144\~168 h,168\~192 h after taking single XZP-3621 tablet. Feces samples will be collected from each subject at a total of 9 time intervals (Only one sample was collected within 24 h before taking single XZP-3621 tablet), And accurate fecal weight will be recorded for each time period. PK blood sample collection: PK blood samples of subjects will be collected before administration (within 2 h before administration) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 h after administration at 18 collection points. Plasma samples for metabolite identification should be separately packaged. Stage 2: This stage of study will be a randomized, open, three-cycle crossover study to evaluate the pharmacokinetic effects and safety of a single oral dose of XZP-3621 in healthy subjects on a high-fat diet versus a standard diet. In this study stage, 24 healthy subjects meeting the requirements of the protocol will be planned to be enrolled and randomly divided into groups A, B, C, D, E and F at 1:1:1:1:1:1 , with 4 subjects in each group. Each subject will undergo three cycles of fasting administration, high-fat postprandial administration, and standard postprandial administration (in random order) throughout the study. PK blood sample collection: PK blood samples will be collected before taking single XZP-3621 tablet (within 2 h before drug administration) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192 h after taking single XZP-3621 tablet in each cycle, with a total of 18 collection points.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Administer a single dose of XZP-3621 tablet after a low-fat meal.
Cycle1(D1-D9): Administer the XZP-3621 tablet on an empty stomach in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet after a standard meal in a single dose on Day19.
Cycle1(D1-D9) : Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet after a standard meal in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet after on an empty stomach in a single dose on Day19.
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, China
AUC0-t(area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
Pharmacokinetic Data Analysis for XZP-3621 and its metabolites
Time frame: up to 192 hours
Cmax(maximum measured concentration of the analyte in plasma)
Pharmacokinetic Data Analysis for XZP-3621 and its metabolites
Time frame: up to 192 hours
AUC0-∞(area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Pharmacokinetic Data Analysis for XZP-3621 and its metabolites
Time frame: up to 192 hours
to determine the Mass Balance recovery of orally administered XZP-3621 and its metabolites in all (urine, faeces and vomits) amount excreted (Ae) expressed as a percentage of the administered dose (%Ae)
cumulative excretions after a single dose of XZP-3621 and its metabolites in urine, feces and vomits.
Time frame: MB stage:Day1-Day9
Tmax(the time from dosing at which Cmax was apparent)
Pharmacokinetic Data Analysis for XZP-3621 and its metabolites
Time frame: up to 192 hours
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE 5.0
Time frame: MB Stage:28±3 days,FE Stage:47±3 days
T1/2(Apparent terminal elimination half-life )
Pharmacokinetic Data Analysis for XZP-3621 and its metabolites
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Cycle1(D1-D9): Administer the XZP-3621 tablet after a standard meal in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet on an empty stomach in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day19.
Cycle1(D1-D9) : Administer the XZP-3621 tablet on an empty stomach in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet after a standard meal in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day19.
Cycle1(D1-D9): Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet on an empty stomach in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet after a standard meal in a single dose on Day19.
Cycle1(D1-D9): Administer the XZP-3621 tablet after a standard meal in a single dose on Day1; Cycle2(D10-D18): Administer the XZP-3621 tablet after a high-fat meal in a single dose on Day10; Cycle3(D19-D27): Administer the XZP-3621 tablet on an empty stomach in a single dose on Day19.
Time frame: up to 192 hours