A Clinical Study to Evaluate the Absorption, Metabolism, and Excretion of Oral [14C]GS1-144 in Healthy Postmenopausal Female Participants

A Clinical Study to Evaluate the Absorption, Metabolism, and Excretion of Oral [14C]GS1-144 in Healthy Postmenopausal Female Participants

This is a single-center, non-randomized, open-label, single-dose clinical PK study in healthy postmenopausal female participants.

This is a single-center, single-dose, open-label design study, planned to enroll 6-8 healthy postmenopausal female participants to evaluate the human mass balance of [14C]GS1-144. Each participant will receive a single oral dose of approximately 30 mg/100 µCi of [14C]GS1-144 oral formulation. During the study, blood, urine, and feces samples will be collected at specified time points/intervals. By measuring the the total radioactivity （TRA ）concentration in whole blood and plasma, and the concentrations of GS1-144, its metabolite M1, and other metabolites (if applicable) in plasma, the PK parameters of TRA of [14C]GS1-144 in plasma and whole blood (if applicable) and the PK parameters of GS1-144, its metabolite M1, and other metabolites (if applicable) in plasma will be calculated, and the distribution of TRA between whole blood and plasma will be determined; by measuring the amount of radioactivity in urine and feces, the TRA recovery, radioactivity excretion data, and main excretion pathways will be obtained; through the analysis of the radioactive metabolite profile in plasma, urine, and feces and the structural identification of major metabolites, the metabolic and elimination pathways of GS1-144 in humans will be determined.

Inclusion Criteria:

1. Healthy postmenopausal female participants meeting the menopause criteria at screening visit: natural menopause (defined as continuous spontaneous amenorrhea ≥ 12 months) or continuous spontaneous amenorrhea ≥ 6 months with serum follicle-stimulating hormone (FSH) > 40 IU/L, or ≥ 6 weeks after bilateral oophorectomy for benign disease (with or without hysterectomy);
2. Age at the time of signing the informed consent form (ICF): 40-65 years old (inclusive);
3. Body mass index (BMI) range of 19-27.9 kg/m2 (inclusive), and body weight not less than 45 kg;
4. Fully understand the purpose and requirements of this study, and voluntarily sign the ICF;
5. Able to communicate well with the study personnel and to complete the study in accordance with the protocol.

Exclusion Criteria:

Auxiliary Examinations:

1. Clinically significant abnormalities found during vital signs, physical examination, chest X-ray (posteroanterior view), ophthalmological examination, digital rectal examination, abdominal B-ultrasound, or gynecologic ultrasound;

2. Abnormal laboratory tests at screening (hematology, blood chemistry, coagulation function, urinalysis, stool routine and occult blood, thyroid function, parathyroid function, sex hormones, see Appendix 2 for details) that are judged by the investigator to be clinically significant;

3. Resting corrected QT interval (corrected using Fridericia's formula, QTcF = QT/RR^1/3) obtained from 12-lead ECG > 460 ms for females; or other abnormalities judged by the investigator to be clinically significant;

4. Clinically significant abnormal results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody IgG (Anti-HCV IgG), treponema pallidum antibody, or human immunodeficiency virus antibody as judged by the investigator;

5. Abnormal serum pregnancy test results judged clinically significant by the investigator; participants with natural menopause, total hysterectomy, or bilateral oophorectomy may be exempted from pregnancy testing;

   Medication History:

6. Use of any prescription drugs within 4 weeks prior to first dose [including but not limited to any drugs that alter liver enzyme activity (e.g., glucocorticoids, sex hormones, anticonvulsants, cyclosporine, etc.)], or use of any over-the-counter drugs (including but not limited to Chinese herbal medicines, Chinese herbal compound preparations, health products, etc.) and vitamin supplements within 2 weeks prior to first dose; including use of cytochrome P450 1A2 (CYP1A2) inducers within 3 months prior to administration of the investigational product, or use of CYP1A2 inhibitors within 2 weeks or 5 half-lives (whichever is longer) prior to administration (see Appendix 1 for details);

   Medical and Surgical History:

7. History of syncope with hypotension, orthostatic hypotension, or hypertension within the past 2 years;

8. History of any clinically significant disease, or any disease or condition that, in the opinion of the investigator, could affect the study results, including but not limited to circulatory, respiratory, endocrine, nervous, digestive, or urinary system, hematological, immunological, psychiatric, and metabolic diseases;

9. History of organic heart disease, cardiac failure, myocardial infarction, angina pectoris, unexplained arrhythmia, Torsades de Pointes, ventricular tachycardia, atrioventricular block, long QT syndrome, or symptoms and family history of long QT syndrome (indicated by genetic proof or sudden cardiac death of a close relative at a young age);

10. History of dysphagia, oesophageal stenosis, or gastrointestinal diseases causing clinically significant symptoms such as nausea, vomiting, diarrhoea, or malabsorption syndrome, or a history of severe vomiting or diarrhoea within one week prior to screening;

11. History of surgery that, in the investigator's judgment, would affect drug absorption, distribution, metabolism, or excretion (e.g., gastrectomy, cholecystectomy, gastric bypass, duodenotomy, colectomy), or have undergone major surgery within 6 months prior to screening or whose surgical incision has not fully healed; major surgery includes, but is not limited to, any surgery with a significant risk of haemorrhage, a prolonged period of general anaesthesia, or incisional biopsy or significant traumatic injury, or planning to undergo surgery during the study;

12. History of any known allergy to drugs, food, or environmental factors, especially allergy to components similar to the investigational product, or having an allergic constitution;

13. Have symptomatic haemorrhoids or perianal diseases accompanied by regular/active haematochezia, irritable bowel syndrome, or inflammatory bowel disease;

14. History of abnormal urination due to congenital or acquired urinary tract stenosis caused by infection/tumor, or bladder dysfunction;

15. Clinically significant major infection within 2 months prior to screening (e.g., requiring hospitalization or parenteral antibacterial therapy), or active systemic bacterial, viral, or fungal infection, or clinically significant pyrexia, or unresolved infection within 2 weeks prior to screening, or a history of herpes zoster within 3 months prior to screening;

16. Known or suspected history of immunodeficiency (e.g., history of frequent recurrent infections), history of hereditary or acquired complement deficiency;

    Lifestyle Habits:

17. Habitual diarrhoea or average bowel movement frequency of less than once per day;

18. Alcohol breath test result > 0 mg/100 mL or alcohol abuse within 3 months prior to screening, i.e., weekly alcohol consumption exceeding 14 units (1 standard unit equals 17.5 mL or 14 g pure alcohol; alcohol content for different types of alcoholic beverages is indicated by volume percentage; 1 standard unit is approximately equivalent to 35 mL of 50° liquor or 350 mL of 5° beer), or unwillingness to stop consuming alcohol or any alcohol-containing products during the study period;

19. Use of tobacco products, nicotine, or nicotine-containing products (e.g., e-cigarettes) within 1 month prior to screening, or unwillingness to stop smoking during the study period;

20. History of drug abuse or drug addiction, or a positive urine drug abuse screen;

21. Excessive consumption (more than 8 cups per day, 1 cup = 250 mL) of tea, coffee, or caffeinated beverages daily within 3 months prior to screening; or intake of any foods or beverages containing or metabolized to produce caffeine or xanthine (e.g., coffee, tea, chocolate, cola, etc.) within 24 hours prior to admission;

22. Have special dietary requirements or are unable to comply with the standardized diet (e.g., intolerance to standard meals); or refusal to abstain from foods or beverages that may affect the metabolism of the investigational product (e.g., foods or beverages containing grapefruit, carambola, or their products, etc.) from 48 hours before dosing until the end of the study;

23. Plan to engage in strenuous exercise during the study;

    Others:

24. Occupation involving long-term exposure to radioactive conditions; or significant radioactive exposure (e.g., ≥2 chest/abdominal CT scans, or ≥3 other types of X-ray examinations) within 1 year prior to screening, or participation in a radiolabeled drug trial within 1 year prior to screening;

25. Have had blood loss or blood donation of >400 mL within 3 months prior to screening, or have had blood loss or blood donation of >200 mL within 1 month prior to dosing, or have received a transfusion of blood or blood components within 1 month, or plan to donate blood during the study drug administration period or within 3 months after discontinuation of the study drug;

26. History of needle phobia or hemophobia, or difficulty with blood collection or inability to tolerate venipuncture blood collection;

27. Have participated in any clinical trial and received an investigational drug or used an investigational device within 3 months prior to screening; or plan to participate in other clinical trials during this study, or not attending the clinical trial in person;

28. Have received any vaccination within 4 weeks prior to screening or plan to receive any vaccination during the study or within 1 month after the end of the study;

29. Have other factors deemed by the investigator to make the participant unsuitable for participation in this study, or participants who withdraw from the study for personal reasons.