A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Oral HRS5091 in Healthy Subjects and Chronic Hepatitis B Patients

Exclusion Criteria

• •Healthy subjects
• •1. Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases.
• •2. Have a digestive system disease or a medical history of severe digestive system disease at present or in the past month.
• •3. Have severe infection, severe trauma or major surgical operations within 3 months. Plan to receive surgery during the trial and within two weeks after the end of the trial.
• •4. 12-ECG test have clinical significant abnormality or the QT interval (QTc) \> 470 ms(male)/QTc)\> 480 ms(male) or\<300ms(female).
• •5. Have a medical history of immune-mediated diseases.
• •6. Screening for infectious diseases is positive,Including HBsAg, Anti-HCV(hepatitis C virus), TPPA(Treponema pallidum particle agglutination assay), Anti-HIV.Treponema pallidum antibody screen positive, at the investigator's discretion in conjunction with RPR(rapid plasma reagin assay) results.
• •7. Suspected allergy to any ingredient in the study drug.
• •8. Have any drug that inhibits or induces liver metabolism within 1 month.
• •9. Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines within 14 days before taking the study drug, or plan to take other drugs during the test period.
• •10. Participated in clinical trials of any drug or medical device within 3 months before screening.
• •11. Had donated blood/blood transfusion≥ 200 mL within 1 months prior to screening or donated blood or blood transfusion≥ 450 mL within 3 months prior to screening.
• •12. The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
• •13. Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
• •14. Pregnant or lactating women;
• •15. Drug screening or alcohol breath test is positive.
• •16. Other conditions that the investigator believes the subject is not suitable.
• •CHB subjects
• •1. Currently suffering from serious cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases other than hepatitis B.
• •2. People have acute or chronic liver disease by non-HBV infection (Whether fatty liver is excluded or not is determined by the investigator).
• •3. Liver stiffness (LSM)\> 12.4 kPa(kilopascal) by noninvasive transient liver elastography (eg Fibroscan®) or recorded liver biopsy suggesting cirrhosis or extensive fibrosis within 6 months before randomization.
• •4. Primary liver cancer, high-risk groups of primary liver cancer or AFP(alpha fetoprotein)\> 50g/L;
• •5. Have clinically demonstrated or history of liver function decompensation, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, splenomegaly, ascites, etc.;
• •6. Laboratory inspection:
• •1. Platelet count \<90×10⁹/L;
• •2. White blood cell count \<3.0×10⁹/L;
• •3. Absolute value of neutrophils \<1.5×10⁹/L;
• •4. Serum total bilirubin\>2×ULN;
• •5. Albumin \<30 g/L;
• •6. Creatinine clearance rate ≤60ml/min;
• •7. INR(international normalized ratio)\>1.5;
• •8. ALT\> 5 ULN on screening/baseline visit
• •7. HIV and/or syphilis antibody positive (Treponema pallidum antibody screen positive, at the investigator's discretion in conjunction with RPR results).
• •8. Subjects who have previously received organ/bone marrow transplantation;
• •9. Have used immunosuppressants, immunomodulators or cytotoxic drugs within 6 months before the study medication;
• •10. Suspected allergy to any ingredient in the study drug.
• •11. 12-ECG test have clinical significant abnormality or the QT interval (QTc) \> 470 ms(male)/QTc)\> 480 ms(male) or\<300ms(female).
• •12. The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
• •13. Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
• •14. Pregnant or lactating women;
• •15. Drug screening or alcohol breath test is positive.
• •16. Other conditions that the investigator believes the subject is not suitable.