Pharmacokinetic Study of Buagafuran Capsules in Participants With Hepatic Impairment and Normal Hepatic Function

Pharmacokinetic and Safety Study of Buagafuran Capsules in Participants With Hepatic Impairment and Normal Hepatic Function

This study adopts a non-randomized, open label, parallel, single-dose design to evaluate the safety and pharmacokinetic characteristics of Buagafuran capsules in participants with hepatic impairment.

This study adopts a non-randomized, open label, parallel, single-dose design to evaluate the safety and pharmacokinetic characteristics of Buagafuran capsules in participants with hepatic impairment.

This study enrolled 24 participants, both male and female. Three experimental groups were set up, with Day1 taking 30 mg Buagafuran capsules on an empty stomach in the morning.Participants can leave on Day3.

Inclusion Criteria:

1. Voluntarily sign an informed consent form before the start of activities related to this trial, understand the procedures and methods of this trial, and be willing to strictly follow the clinical trial protocol to complete this trial;
2. Participants (including partners) are willing to have no fertility plans from screening to within 6 months after the last administration of the study drug, and voluntarily adopt highly effective contraceptive measures;
3. On the day of signing the informed consent form, the age range is 18 to 70 years old (including both ends), and both males and females are eligible;
4. Male participants should weigh no less than 50 kg, and female participants should weigh no less than 45 kg; Body Mass Index (BMI) should be between 18 and 32 kg/m2 (including both ends), with BMI=weight (kg)/height (m2);
5. Creatinine clearance rate ≥ 60 mL/min;
6. Participants with normal hepatic function must also meet all of the following criteria: a): Weight matching with the hepatic impairment group, with an average weight range of ± 10 kg; b): Age matching with the hepatic impairment group, with an average age range of ± 10 years; c): The number of participants of each gender is similar to that of the hepatic impairment group (mean ± 1 participant/gender);
7. Participants with hepatic impairment must also meet all of the following conditions: a): Chronic hepatic impairment caused by primary hepatic diseases, and hepatic impairment patients with Child Pugh classification of A or B; b):The clinical diagnosis is cirrhosis; c): Individuals who have a stable medication regimen for treating hepatic impairment, complications, and other accompanying diseases for at least 14 days prior to taking the investigational drug, and whose medication does not require adjustment; or those who have not taken medication;

Exclusion Criteria:

1. Allergic constitution, including individuals with a history of severe drug allergies or drug hypersensitivity reactions, known to be allergic to the study drug or any component of the study drug;

2. During the screening period, the electrocardiogram showed a QTc interval of>470 milliseconds in males and>480 milliseconds in females;

3. Individuals with a history of swallowing difficulties or any gastrointestinal diseases that affect drug absorption, including frequent nausea or vomiting caused by any underlying cause;

4. Those who need treatment for bacterial, viral, parasitic or fungal infection with any clinical symptoms during screening (excluding hepatitis B and hepatitis C), and those who have a history of serious active infection within 1 month before screening;

5. Individuals who have undergone major surgeries within the previous 6 months (defined as surgeries involving intracranial, chest, abdominal, pelvic, or limb organs that cause significant tissue trauma and require long-term recovery (such as organ transplantation, heart surgery, or joint replacement), or those who plan to undergo surgery during the study period; Individuals with a history of liver transplantation; Participants who have undergone surgery that may affect drug absorption, distribution, metabolism, and excretion in the past (such as gastric and duodenal resection surgery) or who may be hospitalized due to surgery or other reasons during the expected trial period;

6. Screening individuals who have received the vaccine within the previous 14 days or plan to receive the vaccine during the study period;

7. Screening individuals who have donated blood or lost blood ≥ 200 mL within the first 3 months, or plan to donate blood during the trial period or within 1 month after the trial ends;

8. Screening for individuals who have used other clinical trial drugs within the previous 3 months or plan to participate in other clinical trials during the study period;

9. Within one month prior to screening (or 5 times the half-life, whichever is longer), strong or moderate inducers or inhibitors of CYP2B6, CYP3A4, renal transporter inhibitors, etc. have been used;

10. Consuming grapefruit or products containing grapefruit, food or beverages containing caffeine, xanthine, or alcohol (including chocolate, tea, coffee, cola, etc) 48 hours prior to receiving the investigational drug; Those who engage in vigorous exercise or have other factors that affect drug absorption, distribution, metabolism, excretion, etc;

11. Screening for alcoholics within the first 3 months, those who consume more than 14 units of alcohol per week (1 unit=360 mL of beer, 45 mL of strong liquor with an alcohol content of 40%, or 150 mL of wine) or have a positive alcohol screening result; Individuals who smoke an average of 10 or more cigarettes per day within the first 3 months of screening;

12. Individuals with a history of drug use, drug abuse, or positive drug abuse screening;

13. Pregnant or lactating women, or women of childbearing age who test positive for pregnancy;

14. Those who cannot tolerate venipuncture or have a history of needle and blood dizziness;

15. Other reasons why researchers believe it is not suitable for inclusion;

    Participants with normal hepatic function who meet any of the following exclusion criteria need to be excluded:

16. History of hepatic impairment;

17. Individuals who have previously or currently suffered from any clinically serious diseases such as circulatory system, endocrine system, nervous system, digestive system, respiratory system, hematology, immunology, psychiatry, and metabolic abnormalities, or any other diseases that may interfere with the test results;

18. Abnormal physical examination, vital signs, laboratory tests, 12 lead electrocardiogram, abdominal ultrasound and other examinations have clinical significance as determined by the researchers;

19. Those who are positive in any index screening of hepatitis B surface antigen, hepatitis C antibody, HIV antigen/antibody or syphilis antibody;

20. Have used any prescription drugs, over-the-counter drugs, herbal medicines, or supplements within 14 days prior to receiving the investigational drug.

    Participants with hepatic impairment who meet any of the following exclusion criteria must be excluded:

21. Participants have any of the following conditions: acute hepatic function damage caused by various reasons; History of liver transplantation; And researchers believe that patients with liver cirrhosis complicated with the following complications: including but not limited to hepatic failure, hepatic encephalopathy, hepatocellular carcinoma (excluding liver cancer patients who have received curative treatment and have not relapsed; excluding liver cancer patients with BCLC stage 0), and those who have experienced esophageal and gastric variceal bleeding within the past 3 months before screening;

22. The laboratory test results during screening meet any of the following criteria: (a) ALT or AST>10 × ULN; (b) NE#<0.75×109/L；(c) HGB<60 g/L； (d) AFP>100 ng/mL; (e) Platelet count<40 × 109/L; any remaining abnormalities that have clinical significance and have been determined by the researchers to be unsuitable for participation in this trial;

23. Individuals who test positive for HIV antigen/antibody screening; If syphilis antibodies are positive, rapid plasma reagin (RPR) testing should be added. If RPR is also positive, it should be excluded;

24. In addition to the primary liver disease itself, those who have previously or currently suffered from other serious organ systemic diseases, including but not limited to gastrointestinal, respiratory, renal, neurological, blood, endocrine, tumor, immune, psychiatric or cardiovascular diseases, or abnormalities with clinical significance such as physical examination and chest radiograph, and have been determined by the research doctor to be unsuitable for participation in this trial.