Nonalcoholic Steatohepatitis (NASH)
Conditions
Brief summary
This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single- and multiple-oral doses of ZSP1601 on fasted condition, and characterize PK of ZSP1601 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 ZSP1601 or placebo .
Detailed description
The study is a randomized, double-blind phase 1 trial including 3 parts: single ascending dose(SAD) part,multiple ascending dose(MAD) part and postprandial pharmacokinetics part.The primary aims of the study as below: Evaluating the safety and tolerance of single and multiple dose of ZSP1601 in healthy volunteers. Evaluating the fasting and postprandial pharmacokinetic parameters of ZSP1601 in healthy volunteers. Eligible participants will be admitted to the trial center on Day -1. Subjects will be randomly assigned to either experimental groups or placebo groups, according to a randomisation schedule in a (4:1) ratio (8 in per experimental group). Subjects in SAD will receive 25、50、100、175、275、350 mg once daily respectively.Each dose will be administrated after assurance of safety for the former dose. Subjects in MAD will receive 50 or 100 mg once daily for 14days respectively.The treatment in food effect consists of 2 periods,and subjects will receive 100mg on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods.To monitor AEs,record abnormalities (12-lead ECG,Vital signs,Physical examination,Clinical Laboratory),and detect the pharmacokinetics of ZSP1601.
Interventions
DRUGZSP1601 25 mg
ZSP1601 tablet administered orally once daily under fasted condition
DRUGPlacebo 25mg
Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
DRUGZSP1601 50 mg
ZSP1601 tablet administered orally once daily under fasted condition
DRUGPlacebo 50 mg
Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
DRUGZSP1601 100 mg
ZSP1601 tablets administered orally once daily in the fasting state
DRUGPlacebo 100 mg
Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state
DRUGZSP1601 175 mg
ZSP1601 tablets administerekd orally once daily under fasted condition
DRUGPlacebo 175 mg
Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
DRUGZSP1601 275 mg
ZSP1601 tablets administered orally once daily in the fasting state
DRUGPlacebo 275 mg
Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state
DRUGZSP1601 350 mg
ZSP1601 tablets administered orally once daily under fasted condition
DRUGPlacebo 350mg
Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
DRUGPlacebo 100mg
Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition
Sponsors
Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking for Participant, Investigator and Clinical Research Associate
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects are required to meet the following criteria in order to be included in the trial: 1. Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects(including adverse events) of the trial prior to enrollment. 2. Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study. 3. Subjects(including partners)have no gestation plans and must use reliable methods of contraception during the study and until 6 months following the last dose of investigational product. 4. Males and female subjects between 18-50 years (Both inclusive). 5. Body weight is no less than 50kg in males and no less than 45kg in females.Body mass index (BMI) 18≤BMI≤28 kg/m2; BMI is determined by the following equation: BMI = weight/height2 (kg/m2). 6. 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. 7. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses(single,multiple and food effect)of ZSP1601 and placebo. | SAD Group: Up to 4 days, MAD: Up to 17days, FE group: Up to 11 days after first dose |
| Concomitant Medication | UP to 4, 17, 11 days for SAD, MAD, FE part respectively |
| Clinical Laboratory Abnormalities(Blood routine test, serum biochemical test, conventional coagulation examinations, urine examination ) post dose of ZSP1601 and placebo. | UP to 4, 17, 11 days for SAD, MAD, FE part respectively |
| 12-lead ECG Abnormalities following oral dosing of ZSP1601 and placebo. | UP to 4, 17, 11 days for SAD, MAD, FE part respectively |
| Vital signs Abnormalities following oral dosing of ZSP1601 and placebo. | UP to 4, 17, 11 days for SAD, MAD, FE part respectively |
| Physical examination Abnormalities following oral dossing of ZSP1601 and placebo. | UP to 4, 17, 11 days for SAD, MAD, FE part respectively |
| Cardiac color ultrasound(UCG) Abnormalities following multiple oral doses of ZSP1601 and placebo. | Screening, Day17 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CL/F of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F). |
| λz of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound. |
| CLr of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | 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 |
| AUClast（AUC0-t）of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration. |
| Multiple-dose plasma PK parameter: DF of ZSP1601 at steady state | Up to 16 days | DF is defined as the percentage of fluctuation in steady state is 100 \* (Cmax, ss - Cmin, ss)/Cavg, ss. |
| Multiple-dose plasma PK parameter: Cmin of ZSP1601 at steady state | Up to 16days | Cmin is defined as the minimum observed concentration of drug in plasma at steady state. |
| Multiple-dose plasma PK parameter: Rac of ZSP1601 at steady state | Up to 16days | Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1 |
| AUCinf（AUC0-∞）of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time). |
| Cmax of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | Cmax is defined as the maximum observed concentration of drug in plasma. |
| Tmax of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | Tmax is defined as the time to maximum concentration. |
| t1/2z of ZSP1601 | UP to 2, 16, 9 days for SAD, MAD, FE part respectively | t1/2z is defined as the time to decline half of the drug concentration in plasma. |
| Single-dose PK Parameter: Ae of ZSP1601 | Up to Day 2 post-dose | Ae is defined as the amount of unchanged drug excreted in urine or faeces after administration. |
| Single-dose PK Parameter: Fe0-t of ZSP1601 | Up to Day 2 post-dose | Fe0-t is defined as the cumulative excretion rate of the drug in urine and feces. |
Countries
China
Outcome results
None listed