Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH)

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 adhere to the visit schedule and protocol requirements and be available to complete the study.
• 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.
• Male and female subjects aged 18-65 (including 18 and 65).
• B ultrasound confirmed fatty liver.
• NASH diagnosis or NASH phenotypic diagnosis.
• Liver fat ≥10% at baseline (MRI-PDFF)

Exclusion criteria

• Eligible subjects must not meet any of the following exclusion criteria:

• Excessive drinking for 3 consecutive months within 1 year before screening.
• Allergic constitution.
• Subjects who donated blood or bleeding profusely(> 400 mL)in the 3 months preceding study screening.
• Subjects having a history of bariatric surgery or preparing for bariatric surgery recently.
• Subjects having a history of liver transplantation or plans for liver transplantation
• Any diseases that increase the risk of bleeding, such as hemorrhoids, acute gastritis or gastric and duodenal ulcers.
• Liver biopsy indicates cirrhosis or previous clinical diagnosis of cirrhosis.
• Type 1 diabetes mellitus.
• Uncontrolled type 2 diabetes mellitus (HbA1c≥8.0%)。
• Any clinically significant abnormality upon physical examination or in the clinical laboratory tests, history or presence of other causes of liver disease,but not limited to above disorders: hepatitis b or hepatitis c virus (HCV) infection and chronic alcoholic liver disease, drug-induced liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson 's disease, alpha 1 - antitrypsin deficiency, liver, obvious abnormal liver function (ALT and AST acuity 5 x ULN or TBIL acuity 1.5 x ULN), etc.
• Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.
• History of having any special food(including dragon fruit,mango,grapefruit,etc.),strenuous exercises,or other factors may interfere with the absorption, distribution, metabolism, or excretion of drug within 2 weeks prior to screening.
• Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
• Presence of clinically significant abnormalities in ECG or QTcB>450ms in males,or QTcB>470ms in females.
• HIV positive.
• Clinically significant nephropathy or renal dysfunction, blood creatinine >1.5×ULN, eGFR< 60 mL/min/1.73m2 [calculation formula: Ccr:(140-age)× weight (kg) /0.818×Scr(mumol /L), female ×0.85].
• Platelet count <100×109/L.
• Antinuclear antibody (ANA) confirmed positive and clinically significant.
• Abnormal TSH with clinical significance.
• Female during pregnancy and lactation or positive serum pregnancy test.
• Patients with contraindication of MRI scan.
• Take any product contains alcohol within 24 hours prior to dosing.
• Have chocolate, any food or beverage that contains caffeine or xanthine within 24 hours prior to dosing.
• Positive for urine drug screening or history of substance abuse for a period of 5 consecutive years before screening.
• Any acute illness or concomitant medication from screening to first dosing.
• As judged by the researcher, it is not suitable to join the clinical researcher.