Tolerance And Efficacy Of ZSP1601 Tablets In Patients With Nonalcoholic Steatohepatitis For 28 Days

AimTo evaluate the tolerance and efficacy of zsp1601 tablets in the treatment of patients with nonalcoholic steatohepatitis.MethodIn this randomized,double-blind,placebo-controlled multi-dose trial,36 adult patients with Nash diagnosis or Nash phenotype diagnosis [ liver fat ≥ 10%（measured by MRI-PDFF）and alanine aminotransferase ≥ 1.5×ULN at baseline ] were randomly divided into oral zsp1601 tablets 50 mg once daily（QD）,50 mg twice daily（bid）and 100 mg twice daily（bid）for 28 days.Of the 12 subjects in each group,9 received the test drug and3 received placebo.The drug tolerance was assessed by 12 lead ECG,clinical laboratory examination,vital signs and physical examination,including the changes of liver fat content relative to baseline on the 29 th day,the changes of liver biochemical indexes（alanine aminotransferase,aspartate aminotransferase,glutamyltranspeptidase,alkaline phosphatase）and metabolic indexes（body mass index,waist circumference,abdominal circumference,blood glucose and blood lipid）.ResultDuring the study period,zsp1601 tablets in each dose group were safe and tolerable.Most adverse events were grade 1 or 2,and there were no death,withdrawal or serious adverse events.The adverse event rates of zsp1601 tablets 50 mg QD group,50 mg bid group and 100 mg bid group were 77.8%,66.7% and 88.9% respectively.Adaptive headache was the most common adverse event and occurred only in the 100 mg twice daily（bid）group（14.7%）.On the 29 th day,the relative change rates of liver relative fat content in placebo group and zsp1601 tablets 50 mg QD group,50 mg bid group and 100 mg bid group were-12.80%,-12.43%,-21.88% and-21.50% respectively;The relative change rates of alanine aminotransferase compared with baseline were-14.06%,-20.93%,-35.69%and-49.03% respectively.There was significant difference between 50 mg twice daily（bid）group and 100 mg twice daily（bid）group and placebo group（P = 0.0225 and P = 0.0003）;The relative change rates of aspartate aminotransferase compared with baseline were-12.06%,-16.87%,-28.76% and-42.51%,respectively.There was significant difference between 100 mg twice daily（bid）group and placebo（P = 0.0115）.Compared with placebo group,the average cholesterol level of zsp1601 tablets in 50 mg twice daily（bid）group and100 mg twice daily（bid）group decreased significantly compared with baseline（P = 0.005 and P = 0.025）;Compared with the placebo group,the serum low density lipoprotein cholesterol and triglyceride in each dose of zsp1601 tablet group did not increase.ConclusionZSP1601 tablet has good tolerance and obvious curative effect in the treatment of NASH patients for 28 days,improves hepatic steatosis and inflammation,significantly reduces cholesterol,and does not increase serum low-density lipoprotein cholesterol and triglyceride.