Safety, Tolerability and Pharmacokinetic Characteristics Evaluation on GST-HG121 Tablets

Overview

This phase I clinical study is a phase I clinical study on the safety, tolerability, pharmacokinetic characteristics and food effects of single / continuous administration in Chinese adult healthy subjects

This study will be divided into three parts: single dose escalation (SAD) study, multiple dose escalation (MAD) study and food impact study. The sad study and mad study adopted a randomized, double-blind, placebo-controlled, dose increasing trial design to evaluate the safety, tolerability and pharmacokinetic characteristics of gst-hg121 tablets. A randomized, two cycle, double crossover trial design was adopted for the study of food effects. Healthy Chinese adult volunteers were randomly divided into two groups. In the first cycle, the drug was administered on an empty stomach and after a meal, and in the second cycle, the drug was administered on an empty stomach and after a meal to evaluate the effects of food on the pharmacokinetic characteristics of gst-hg121 tablets. Part I: Study on single dose increment A total of 5 dose groups were set for a single administration: 5mg (group I), 15mg (Group II), 30mg (Group III), 60mg (Group IV) and 100mg (Group V). According to the safety, tolerance and PK parameters of group V, higher dose group studies (150mg and 200mg are not excluded). There were 10 subjects in each group, of which 8 received gst-hg121 tablets and 2 received placebo. Therefore, it is planned to recruit 50 subjects to study the safety, tolerance and pharmacokinetics of single administration. Each group was administered once, and gst-hg121 tablet or placebo was orally administered once under the fasting condition of D1. The subjects will be kept in the hospital to observe the vital signs and whether there are adverse events. Safety inspection is required at D2, D4 and D6, tolerance evaluation is required at D6, and pharmacokinetic indexes of gst-hg121 are detected at the same time. Subjects in different dose groups will be enrolled in the group in turn. After all the subjects in one group have completed the evaluation, the researchers and the sponsor will jointly evaluate the safety, tolerance and PK parameters under the dose level to determine whether to conduct the next dose group study. If necessary, relevant clinical experts can be invited to consult and make decisions. After obtaining the PK report of the first dose group, it is possible to adjust the time point of collection or inspection of PK samples or other inspection items. After the completion of all 5 dose groups, the single dose increment test will be terminated. If the tolerance and safety of the drug at the highest dose are good, the investigator and the sponsor shall conduct a comprehensive evaluation, and it is not excluded to conduct the trial of the higher dose standby group (\> 100mg). Part II: Study on multiple dose escalation According to the results of single dose study, it is planned to select 1-3 dose groups within the range of single dose for oral administration test for 7 consecutive days (the specific dose group is determined according to the results of single dose increment test). There were 12 subjects in each group, of which 10 received gst-hg121 tablets and 2 received placebo. Therefore, it is planned to recruit 36 subjects for safety, tolerance and pharmacokinetics study of multiple administration. From D 1 to d 7, take gst-hg121 tablets or placebo orally on an empty stomach once a day (the specific administration frequency may be adjusted based on the results of the single dose increment test). After the first administration, conduct safety inspection on D3, D6 and D12, and conduct tolerance evaluation on D12. After a group of subjects have completed the evaluation, the researcher and the sponsor will jointly evaluate the safety, tolerance and PK parameters at the dose level to determine whether to conduct the next dose group study. If necessary, relevant clinical experts can be invited to consult and make decisions. After obtaining the PK results of the first dose group in the multiple dose increment test, it is possible to adjust the time point of collection or inspection of PK samples or other inspection items. After the multiple dose increasing test is terminated, the investigator and the sponsor shall conduct comprehensive evaluation, and it is not excluded to select other doses within the safe dose range for further test. Part III: Food impact study The 30mg (Group III) dose group or 60mg (Group IV) dose group (the final dose is determined according to the results of the single dose study) is tentatively determined, and the single dose, food impact and drug metabolism and transformation studies need to be completed. 18 subjects are planned to be enrolled into the group and divided into two groups: 10 subjects in group A (including 8 subjects receiving gst-hg121 tablets and 2 subjects receiving placebo) and 8 subjects in group B (all receiving gst-hg121 tablets). Subjects in group a need to participate in the study on the effects of single administration of 30mg or 60mg and food on pharmacokinetics, and subjects in group B need to participate in the study on the effects of food on pharmacokinetics and drug metabolism and transformation. In group A, the first cycle was administered under the fasting condition of D1, and the second cycle was administered under the standard postprandial condition of one day of d8-d15. In group B, the first cycle was administered under the standard postprandial condition of D1, and the second cycle was administered under the fasting condition of one day of d8-d15. The two cycles were administered alternately, and the cleaning period was 7-14 days (the cleaning period was determined according to the results of the single administration study). The administration study of group A under fasting condition is equivalent to the single administration study of 30mg or 60mg gst-hg121 tablets. After the first administration, the safety inspection was conducted on D2, D4 and D6, and the tolerance evaluation was conducted on D6. If the first administration of group A is completed and the tolerance evaluation result indicates that it can be tolerated, the second cycle of group A and the first cycle of group B can be carried out. During the trial, blood samples will be collected from the subjects at the time point planned in the protocol for pharmacokinetic analysis. As gst-hg121 tablet has not been applied in human body and there is no human PK parameter for reference, this study will be conducted by sentinel enrollment. Group I, group II, group III, group IV, group A and group V: two subjects were enrolled first (two subjects received the test drug gst-hg121 tablets, half male and half female), and the remaining eight subjects were enrolled after at least 48 hours of observation (the two subjects in the first group need to take blood samples and complete the drug concentration detection and data analysis. If it is necessary to fine tune the PK sample collection time point, it can be adjusted in group II). The fourth group (group B) included 8 subjects (all taking the test drug gst-hg121). Two subjects (taking the test drug gst-hg121 tablets, half male and half female) were enrolled in each dose group after multiple administration, and the remaining 10 subjects were enrolled in the group after at least 72 hours of observation.

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