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This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single-and multiple-oral doses of ZSP0678 on fasted condition, and characterize PK of ZSP0678 on an empty stomach (fasted condition) and following a high fat, high calorie meal (fed condition) in a 2-period, 2-sequence manner. The study will be conducted in 3 parts (Ascending single dose, multiple dose and food effect). Participants will receive either ZSP0678 or placebo .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZSP0678-10mg (single dose)-Cohort 1 | Experimental | ZSP0678/Placebo 10mg |
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| ZSP0678-30mg (single dose)-Cohort 2 | Experimental | ZSP0678/Placebo 30 mg Enrollment into Cohort 2 will begin upon assurance of safety for Cohort 1. |
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| ZSP0678-60mg (single dose)-Cohort 3 | Experimental | ZSP0678/Placebo 60mg Enrollment into Cohort 3 will begin upon assurance of safety for Cohort 2. |
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| ZSP0678-120mg (single dose)-Cohort 4 | Experimental | ZSP0678/Placebo 120mg Enrollment into Cohort 4 will begin upon assurance of safety for Cohort 3. |
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| ZSP0678-180mg (single dose)-Cohort 5 | Experimental | ZSP0678/Placebo 180mg Enrollment into Cohort 5 will begin upon assurance of safety for Cohort 4. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZSP0678-10mg | Drug | ZSP0678 tablet administered orally under fasted condition |
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| Measure | Description | Time Frame |
|---|---|---|
| Number and severity of adverse events (AEs) and Serious Adverse Events(SAE) following oral doses of ZSP0678 and placebo. | SAD Group: Up to 5 days, MAD: Up to 18 days, FE group: Up to11 days after first dose ] | |
| Tmax | The time after dosing when Cmax occurs | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| Cmax | Maximum concentration | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| t1/2 | t1/2 is defined as the time to decline half of the drug concentration in plasma. | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| AUCinf(AUC0-∞) | Area under the curve extrapolated until time is infinity (AUCinf) | UP to 5, 18, 11 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. | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| CL/F | CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F). | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| λz |
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Inclusion Criteria:
Subjects are required to meet the following criteria in order to be included in the trial:
Signature signed informed consent before the trial, and fully understood the content, process and possible adverse reactions.
Subjects must be willing and able to complete the research according to the experimental protocol.
Subjects (including partners) are willing to take effective contraceptive measures and have no pregnancy plan during the whole study period until 6 months after drug withdrawal.
Male and female subjects aged 18-50 (including 18 and 50)
Body weight of male subjects should not be less than 50kg and that of female subjects should not be less than 45kg.Body mass index (BMI) = weight (kg)/height 2 (m2), the range of 19~26kg/m2 (including the critical value);
Physical condition:No significant abnormalities in medical history, including cardiovascular system, liver, kidneys, gastrointestinal system, neural system, respiratory system (eg.asthma,asthma induced by exercise,chronic obstructive pulmonary disease), mental, metabolism, etc.
Subjects in general good health or No significant abnormalities in the opinion of the investigator as determined by vital signs and a physical examination.
Exclusion Criteria:
Eligible subjects must not meet any of the following exclusion criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Friendship Hospital Affiliated to Capital Medical Universit | Beijing | Beijing Municipality | 100050 | China |
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| ZSP0678-240mg (single dose)-Cohort 6 | Experimental | ZSP0678/Placebo 240mg Enrollment into Cohort 6 will begin upon assurance of safety for Cohort 5. |
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| ZSP0678-320mg (single dose)-Cohort 7 | Experimental | ZSP0678/Placebo 320mg Enrollment into Cohort 7 will begin upon assurance of safety for Cohort 6. |
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| ZSP0678 (food effect)-Cohort FE | Experimental | Period 1: Group A and Group B receive ZSP0678/Placebo under the fasting or fed condition ,respectively on Day1. Period 2: Group A and Group B receive ZSP0678/Placebo under the fed or fasting condition ,respectively on Day8. Enrollment into Cohort FE will begin upon assurance of safety for Cohort 4. |
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| ZSP0678 Dose1 (multiple doses)-Cohort 8 | Experimental | ZSP0678/Placebo Dose1 will be administrated according to the results of Cohort 2&3 |
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| ZSP0678 Dose2 (multiple doses)-Cohort 9 | Experimental | ZSP0678/Placebo Dose2 will be administrated according to the results of Cohort 3&4 |
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| ZSP0678 Dose3 (multiple doses)-Cohort 10 | Experimental | ZSP0678/Placebo Dose3 will be administrated according to the results of Cohort 4&5 |
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| ZSP0678-30mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678-60mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678-120mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678-180mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678-240mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678-320mg | Drug | ZSP0678 tablets administered orally under fasted condition |
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| ZSP0678 | Drug | ZSP0678 tablets administered orally under fasted or fed condition |
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| ZSP0678-Dose 1 | Drug | ZSP0678 tablets administered orally once daily for 14 Days |
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| ZSP0678-Dose 2 | Drug | ZSP0678 tablets administered orally once daily for 14 Days |
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| ZSP0678-Dose 3 | Drug | ZSP0678 tablets administered orally once daily for 14 Days |
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| ZSP0678 Placebo | Drug | Participants will receive placebo matching to ZSP0678 orally. |
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λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
| UP to 5, 18, 11 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. | UP to 5, 18, 11 days for SAD, MAD, FE part respectively |
| Multiple-dose plasma PK parameter: Rac of ZSP0678 at steady state | Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1 | UP to 18 days. |
| Multiple-dose plasma PK parameter: DF of ZSP0678 at steady state | DF is defined as the percentage of fluctuation in steady state is 100 * (Cmax, ss - Cmin, ss)/Cavg, ss. | UP to 18 days. |
| Multiple-dose plasma PK parameter: Cmin of ZSP0678 at steady state | Cmin is defined as the minimum observed concentration of drug in plasma at steady state. | UP to 18 days. |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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