Study on the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets

Launched by FUJIAN COSUNTER PHARMACEUTICAL CO. LTD · Apr 28, 2021

Keywords

ClinConnect Summary

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.

Gender

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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\<90×10\^9/L; leukocyte count\<3.0×10\^9/L; neutrophil absolute value\<1.3×10\^9/L; serum total bilirubin\>2×ULN; albumin\<30 g/L; creatinine clearance rate≤60ml/min (calculated by MDRD formula); international standardization ratio value of prothrombin time (INR) \>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.