GS1-144 in Participants with Hepatic Impairment and Healthy Female

Pharmacokinetic Study of GS1-144 Tablets in Female Participants with Hepatic Impairment and Healthy Female Participants

Inclusion Criteria:

• Participants who sign the ICF prior to the trial, have a full understanding of the trial content, procedures, and possible adverse reactions, and are able to complete the study in accordance with the protocol requirements。

• Female participants aged 18-70 years (inclusive) (age-matched between the normal hepatic function group and the hepatic impairment groups, mean ±10 years).

• Females of childbearing potential who are willing to use adequate and effective contraception from the date of signing the ICF until 1 month after administration of the investigational drug.

• Body weight ≥ 45.0 kg (body weight matched between the normal hepatic function group and the hepatic impairment groups, mean body weight ±10 kg), with BMI within 18.0-32.0 kg/m2 (inclusive).

• For participants with normal hepatic function, findings from physical examination, vital signs, clinical laboratory tests (hematology, blood chemistry, urinalysis, coagulation tests, thyroid function test [FT3, FT4, and TSH], and parathyroid hormone), Chest x-ray (PA), abdominal ultrasound examinations, etc., are normal or abnormal without clinical significance.

• For participants with hepatic impairment, the following inclusion criteria must also be met to be eligible for this study:

  1. Hepatic impairment caused by hepatitis B, hepatitis C, autoimmune hepatitis, nonalcoholic fatty liver disease, alcoholic liver disease, etc., with Child-Pugh classification assessed as Class A/mild (Child-Pugh score: 5-6) or Class B/moderate (Child-Pugh score: 7-9)
  2. A stable medication regimen for the treatment of hepatic impairment, complications, and/or other concomitant diseases for at least 14 days prior to screening, with no need for modification (e.g., medication type, dose, or dosing frequency); or not receiving medication.
  3. Clinical laboratory tests: absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1,000/mm3), platelets (PLT) ≥ 35.0 × 109/L (35,000/mm3), hemoglobin (HGB) ≥ 8.0 g/dL (80 g/L), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal (ULN), creatinine clearance (CLcr, calculated using the Cockcroft-Gault formula) ≥ 60 mL/min.
  4. Systolic blood pressure 90-159 mmHg (Inclusive), diastolic blood pressure 60-99 mmHg (inclusive), and pulse rate 50-100 beats per minute (bpm, inclusive).

Exclusion Criteria:

• Allergic constitution (e.g., allergy to more than two drugs or foods), or a history of allergy to the investigational drug or any excipients thereof.
• Use of tobacco-containing products, nicotine, or nicotine-containing products (e.g., e-cigarettes) within 1 month prior to screening, or unwillingness to stop smoking during the study.
• Alcohol abuse within 3 months prior to screening (weekly consumption ≥ 14 units of alcohol: 1 unit = 360 mL of beer, or 45 mL of spirits with an alcohol content of 40%, or 150 mL of wine), or unwillingness to stop drinking during the study.
• Blood loss or donation of ≥ 450 mL of whole blood or plasma within 3 months prior to screening, or receipt of any transfusion of blood or blood products within 60 days.
• Use of CYP1A2 inducers or CYP1A2 inhibitors within 1 month or within 5 half-lives prior to screening (whichever is longer), and throughout the study (except stable concomitant medications for participants with hepatic impairment).
• Use of any of the following drugs within 1 month or within 5 half-lives prior to screening (whichever is longer) (including vitamins, hormonal contraceptives, hormone replacement therapy [HRT], and traditional Chinese medicines, herbal medicines, and Chinese patent medicines [e.g., St. John's wort]), except for occasional use of acetaminophen (≤ 2 g/day), topical dermatologic medications (including corticosteroids), and stable concomitant medications for participants with hepatic impairment.
• Clinically significant abnormal 12-lead ECG findings [e.g., tachycardia/bradycardia requiring drug treatment, second- to third-degree atrioventricular block, or QTcF > 470 ms (corrected by Fridericia's formula), or other clinically significant abnormalities], and deemed by the investigator as unsuitable for participation.
• Participation in any clinical study within 3 months or within 5 half-lives prior to screening (whichever is longer) (except those who did not receive treatment).
• Severe infection, trauma, gastrointestinal surgery, portosystemic shunt, or other major surgeries within 4 weeks prior to screening.
• Pregnancy, lactation, or a positive serum pregnancy test.
• Consumption of excessive amounts of tea, coffee, or caffeinated beverages (≥8 cups per day; 1 cup = 250 mL) within 3 months prior to screening; or intake of any food or beverage containing caffeine or xanthine, or that may produce caffeine or xanthine metabolites after ingestion (e.g., coffee, tea, chocolate, cola) within 1 day prior to dosing.
• Positive urine drug screening (including morphine, methamphetamine, ketamine, 3,4-methylenedioxymethamphetamine [MDMA], tetrahydrocannabinolic acid, or cocaine). Positive alcohol breath test.
• Any other condition deemed by the investigator to make the participant unsuitable for participation in this study.
• Participants with normal hepatic function with a history or current serious disease of the gastrointestinal, respiratory, renal, neurologic, hematologic, endocrine, immune, psychiatric, or cardio-cerebrovascular systems.
• Participants with normal hepatic function who test positive for any of the following: hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus antibody (HIV Ab), or TP Ab.
• participants with hepatic impairment with History of liver transplantation.
• participants with hepatic impairmen with liver failure or drug-induced liver injury, or with hepatic encephalopathy, hepatocellular carcinoma (except BCLC stage 0), esophageal and gastric variceal rupture bleeding, or other cirrhosis-related complications deemed by the investigator as unsuitable.
• participants with hepatic impairmen in addition to the primary liver disease, a history or current serious disease of the gastrointestinal, respiratory, renal, neurologic, hematologic, endocrine, immune, psychiatric, cardiovascular, or cerebrovascular systems, or clinically significant laboratory or other test abnormalities that, in the opinion of the investigator, would make them unsuitable for participation.
• participants with hepatic impairmen with positive HIV antigen/antibody screening; if TP Ab is positive, an additional RPR test is required; if the RPR is also positive, the participant must be excluded.