A Clinical Trial of HRS5580 for Injection Combined With Palonosetron Hydrochloride for the Prevention of Postoperative Nausea and Vomiting

Inclusion Criteria: 1. Voluntarily sign the informed consent form prior to the start of any trial-related activities, fully understand the purpose and significance of the study, and voluntarily comply with the trial procedures; 2. 2、Scheduled to undergo elective surgery under general anesthesia with an expected surgical duration of ≥ 2 hours (surgery types include gynecological surgery, hepatobiliary surgery, intestinal surgery, urological surgery, etc.); 3. Aged ≥ 18 years; 4. Body Mass Index (BMI) between 18 kg/m² and 28 kg/m² (inclusive); 5. American Society of Anesthesiologists (ASA) Physical Status Classification I or II; 6. Expected postoperative hospital stay ≥ 72 hours; 7. Presence of ≥ 3 risk factors for PONV (female, history of PONV or motion sickness, non-smoker, postoperative opioid use); 8. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and must not be breastfeeding; female participants of childbearing potential must use highly effective contraceptive measures (see Appendix 13.1.2) from 30 days prior to the screening period until 6 months after the last dose, and have no plans for egg donation or pregnancy; male participants with a female partner of childbearing potential must use highly effective contraceptive measures from the time of signing the informed consent form until 6 months after the last dose. Exclusion Criteria: 1. Patients with a history of vestibular disorders (including but not limited to: peripheral vestibular syndrome, central vestibular syndrome, etc.) or dizziness (excluding history of motion sickness), or a history of central nervous system disorders that may cause nausea and vomiting; 2. History of chronic nausea or vomiting/retching; 3. History of new-onset myocardial infarction or unstable angina pectoris within 6 months prior to screening, or history of severe cardiac arrhythmias such as second-degree or higher atrioventricular block, or history of New York Heart Association (NYHA) Functional Classification Class II or higher; 4. Any other medical condition that, in the investigator's judgment, may confound the assessment of postoperative nausea and/or vomiting. 5. Random blood glucose \> 11.1 mmol/L during the screening period; 6. Prolonged QTc interval during the screening period: \> 450 ms in males, \> 470 ms in females; 7. Systolic blood pressure ≥ 160 mmHg or \< 90 mmHg, and/or diastolic blood pressure ≥ 100 mmHg or \< 60 mmHg from the time of signing the ICF to before entering the operating room, which is considered clinically significant by the investigator; 8. Abnormal liver function during the screening period: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or gamma-glutamyl transferase (GGT) ≥ 3.0 × ULN and/or total bilirubin (TBIL) ≥ 1.5 × ULN; 9. Abnormal renal function during the screening period: serum creatinine (Cr) ≥ 1.5 × ULN and/or participants undergoing dialysis; 10. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody during the screening period; 11. Known allergy or contraindication to NK-1 receptor antagonists and/or 5-HT3 receptor antagonists and other medications that may be used during the trial; 12. Receipt of any treatment with potential antiemetic effects, including pharmacological and non-pharmacological treatments, within 48 hours prior to the start of investigational product administration (refer to the Prohibited Concomitant Treatments table); 13. Participants whose last use of an opioid occurred less than 5 half-lives before the start of investigational product administration; 14. Use of strong CYP3A4 inducers, strong inhibitors, or specific CYP2D6 substrates within 28 days prior to randomization. 15. Participants who have received chemotherapy within 4 weeks prior to surgery; 16. Use of other medications that may affect antiemetic efficacy as determined by the investigator, with the last use occurring less than 5 half-lives before the start of investigational product administration (based on the actual drug label; if the half-life is unknown, a 48-hour washout period should be applied). 17. Participants scheduled to receive anesthetic methods not specified in the protocol, including local anesthesia, regional anesthesia \[e.g., nerve block, neuraxial block (including subarachnoid block, epidural anesthesia, or combined spinal-epidural anesthesia)\], and total intravenous anesthesia; 18. Participants expected to require an in-place nasogastric tube or orogastric tube after surgery completion; 19. Participants expected to be transferred to the ICU for sedation with endotracheal intubation after surgery or those unable to undergo nausea and vomiting record assessments; 20. Participation in another clinical study of a drug or device within 3 months prior to screening (having signed informed consent and received investigational product/device treatment); 21. Daily excessive consumption of tea, coffee, grapefruit/grapefruit juice, pomelo juice, or caffeinated beverages (average \> 8 cups per day, 200 mL per cup) within 14 days prior to randomization; 22. Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in this trial.

Reproduced word-for-word from the public registry record — the study team can answer questions about it.