Effect of Itraconazole on the Pharmacokinetics of Intravenous HRS-4642 in Healthy Participants

Inclusion Criteria:

1. Healthy participants aged 18 to 45 years (inclusive) at the time of signing the informed consent form.
2. Male participants with a body weight of at least 50.0 kg and female participants with a body weight of at least 45.0 kg, and a body mass index between 19 and 26 kg/m² (inclusive).
3. Women of childbearing potential who have not undergone surgical sterilization must use highly effective contraception from signing the informed consent form until 1 month after the last dose of HRS-4642. Male participants with female partners of childbearing potential must also use highly effective contraception during the same period. Women of childbearing potential must have a negative serum human chorionic gonadotropin test within 14 days before the first dose and must not be breastfeeding.
4. Participants who are able to communicate effectively with the investigator, understand and comply with all study requirements, and voluntarily sign the informed consent form.

**Exclusion Criteria:**

1. History or presence of any clinically significant serious disease involving the cardiovascular, endocrine, neurological, gastrointestinal, respiratory, genitourinary, hematological, immunological, psychiatric, or metabolic systems, or any other condition that may interfere with the study results.
2. Poorly controlled or severe cardiovascular or cerebrovascular disease, or arterial or venous thrombotic events within 6 months before study entry, including cerebral hemorrhage, cerebral infarction, severe or unstable angina, symptomatic congestive heart failure (New York Heart Association Class II-IV), myocardial infarction, arrhythmias requiring medical intervention, or deep vein thrombosis.
3. Carotid artery stenosis of at least 50% on ultrasonography (preferably assessed using the European Carotid Surgery Trial method), or the presence of more than two high-risk plaque features.
4. Low-density lipoprotein cholesterol, total cholesterol, or triglyceride levels above the upper limit of the study site's reference range at screening, or moderate or higher risk of atherosclerotic cardiovascular disease as assessed by the investigator according to the Chinese Guidelines for Lipid Management (2023).
5. History of surgery within 6 months before screening or planned surgery during the study.
6. History of any surgery affecting gastrointestinal absorption, including gastrectomy, intestinal resection, or bariatric surgery, or a need for gastric acid-neutralizing medications during the study.
7. Blood donation or significant blood loss of at least 400 mL, blood transfusion, or use of blood products within 3 months before screening.
8. History of severe drug allergy or hypersensitivity reactions, or known hypersensitivity to HRS-4642 injection, itraconazole, or any of their excipients.
9. Regular use of sedatives, hypnotics, or other addictive medications; history of drug abuse within 1 year before screening; or a positive urine drug abuse screening test.
10. Use of potentially hepatotoxic medications, such as dapsone, erythromycin, fluconazole, ketoconazole, or rifampicin, for more than 7 consecutive days within 6 months before screening.
11. Participation in any clinical trial involving administration of an investigational drug within 3 months before the first dose.
12. Use of medications affecting hepatic enzyme activity or P-glycoprotein activity within 28 days before administration of the study drug.
13. Use of any prescription medications or traditional herbal supplements within 1 month before the first dose, or any over-the-counter medications or dietary supplements, including vitamins and calcium supplements, within 2 weeks before the first dose.
14. Smoking more than 5 cigarettes per day within 3 months before screening and inability to abstain from tobacco products during the study.
15. Regular alcohol consumption exceeding 14 units per week within 6 months before screening and inability to abstain from alcohol during the study, or a positive alcohol breath test. One unit of alcohol is equivalent to 285 mL of beer, 25 mL of spirits, or 100 mL of wine.
16. Clinically significant abnormalities in vital signs, physical examination, 12-lead electrocardiogram, abdominal ultrasonography, chest radiography, hematology, blood biochemistry, urinalysis, or coagulation tests during screening.
17. Positive screening results for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, or human immunodeficiency virus antibody.
18. Consumption of and unwillingness to abstain from methylxanthine-containing foods or beverages, such as coffee, tea, cola, or chocolate, from 48 hours before the first dose until study withdrawal; consumption of and unwillingness to abstain from grapefruit-containing foods or beverages from 14 days before the first dose until study withdrawal; or special dietary requirements that prevent compliance with standardized meals.
19. History of fainting in response to needles or blood, difficulty with blood collection, or inability to tolerate venipuncture.
20. Pregnant or breastfeeding women.
21. Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in the study.