study on the tolerability, pharmacodynamics and pharmacokinetics of gst-hg141 tablets

Conditions: Hepatitis B

Summary: to evaluate the tolerability, pharmacodynamics and pharmacokinetics of gst-hg141 tablets in multiple-center, randomized, double-blind, placebo-controlled multiple-dose, multiple-administration study in patients with chronic hepatitis b (chb)

this study includes 3 cohorts of 25 mg bid, 50 mg bid and 100 mg bid. 30 patients with chronic hepatitis b will be enrolled in this study and each cohort will enroll 10 patients (gst-hg141 tablets : pbo=8:2). all enrolled patients will be given research drugs twice a day for 28 days (d28 was administered only once in the morning). and each cohort requires at least 4 subjects with elevated alt. tolerability, pharmacodynamics and pharmacokinetics will be evaluated according to the protocol.

Eligibility criteria:
inclusion criteria: 1. sign the informed consent before the study and fully understand the content and process of the study as well as the possible adverse drug reactions; 2. be able to complete the study in accordance with protocol requirements; 3. subjects (including partners) are willing to take effective contraceptive measures from completion of screening to 6 months after the last administration; 4. ages ranged from 18 to 70 years old (including 18 and 70 years old); 5. male subjects weighing no less than 45 kg, and female subjects weighing no less than 40 kg. \[body mass index (bmi) = body weight (kg) / height 2 (m\^2)\], body mass index is in the range of 18 \~ 32 kg / m\^2 (including critical value); 6. patients with hbsag-positive for at least 6 months (based on outpatient/inpatient medical records or laboratory report; or with igm hbcab-negative and hbsag-positive when screening; 7. patients without interferon/nucleoside analogue treatment when screening, or interferon treatment was stopped more than 1 year ago, and nucleoside analogue treatment was stopped more than 6 months ago. 8. for hbeag-positive patients, hbv dna ≥ 2×10\^5 iu/ml; for hbeag-negative patients, hbv dna ≥ 2×10\^4 iu/ml; 9. patients with serum alt less than 5×uln when screening. exclusion criteria: 1. patients with suspected allergy to any component of the study drug or allergic constitution (multiple drug and food allergy)； 2. patients who had major trauma or large surgical operation within 3 months before screening or are planning to take surgical treatment during the study ; 3. patients who had blood donation or massive blood loss (≥400 ml), or had a blood transfusion within 3 months before screening; or had blood donation or massive blood loss (≥200 ml) within 1 months before screening; 4. patients with smoking more than 5 cigarettes per day within 3 months before the study or heavy drinking within 4 weeks before screening (drinking more than 14 units of alcohol per week: 1 unit = 285 ml of beer, or 25 ml of spirits, or 100 ml of wine)； 5. patients who had used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or had received live attenuated vaccine within 1 month before screening; 6. patients who used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or who had received live attenuated vaccine within 1 month before screening; 7. patients with clinically significant acute or chronic liver disease caused by non hbv infection (fatty liver disease is ruled out or recruited by researcher); 8. patients with history of liver cirrhosis or progressive liver fibrosis (e.g., liver histopathology reported liver cirrhosis or endoscopy indicated esophageal and gastric varices); 9. patients with confirmed or suspected decompensated hepatitis b cirrhosis including but not limited to: hepatic encephalopathy, hepatorenal syndrome, esophageal and gastric variceal bleeding, splenomegaly, ascites, primary liver cancer, etc. ; 10. patients with history of other malignancies or complicating with other malignant tumors; 11. patients complicating with severe circulatory, digestive, respiratory, urinary, blood, metabolism, immune, nervous and other systemic; 12. patients with acute infection within 2 weeks before screening; 13. patients who had participated in clinical trials of drugs or medical devices within 1 month before screening; 14. patients who could not ban smoking, drinking, caffeinated food or drinks within 2 days before administration and during the study , and patients who have special dietary requirements and can not follow the unified diet; 15. laboratory examination: platelet count\ 2×uln; albumin\ 1.5; 16. patients with alpha fetoprotein (afp) more than 50 ug / l or imaging findings of malignant liver lesions; 17. patients with hcab-positive , aids ag/ab-positive, or positive syphilis spirochemical ab simultaneously rpr test-positive; 18. for patients with normal alt or less than 2×uln, lsm≥12.4 kpa; or for patients with alt≥2×uln, lsm≥17.0 kpa; 19. patients with positive urine drug screening (morphine, marijuana) or alcohol breath test; 20. patients with positive urine drug screening (morphine, marijuana) or alcohol breath test； 21. patients with other factors that are not suitable to participate in this study in researcher's thought.