Evaluation of Safety and Efficacy of Nalbuphine Versus Morphine for Postoperative Analgesia

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase III Clinical Study to Evaluate the Efficacy and Safety of Nalbuphine Versus Morphine for the Treatment of Postoperative Analgesia

Evaluation of safety and efficacy of Nalbuphine versus Morphine patient controlled intravenous analgesia (PCIA) for the treatment of postoperative analgesia

Inclusion Criteria:

1. Age 18-65 years (inclusive), regardless of gender.
2. Weight 45-100 kg (inclusive) and BMI 18.0-30.0 kg/m² (inclusive).
3. Preoperative ASA Physical Status Class I-III.
4. Scheduled for elective general anesthesia in abdominal surgery (single incision ≥5 cm) or orthopedic surgery (limb/joint procedures); completed anesthesia recovery within 4 hours postoperatively, with NRS score ≥4, and willingness to accept protocol-defined analgesia.
5. Ability to comprehend study objectives, operate PCIA devices, and communicate effectively with investigators.
6. Female subjects must be non-pregnant, non-lactating, and agree to use contraception (including partners) for 3 months post-study.
7. Voluntary participation with signed informed consent.

Exclusion Criteria:

1. Known or suspected allergy/hypersensitivity to any component of the investigational product, other opioids, or contraindicated drugs specified in the protocol .

2. Neurological/psychiatric disorders including:

   1. Clinically significant neurological diseases (e.g., epilepsy, cognitive impairment) .
   2. History of brain injury, increased intracranial pressure, or psychiatric disorders (e.g., schizophrenia, bipolar disorder, depression, anxiety) that may interfere with safety or study assessments as judged by the investigator .

3. Cardiovascular diseases/history:

   1. Severe cardiovascular conditions (NYHA Class II or higher), myocardial infarction, angina, or severe arrhythmia within the past year .
   2. Abnormal 12-lead ECG findings during screening (e.g., sinus bradycardia ≤55 bpm, ≥Grade II AV block) deemed unsuitable by the investigator .
   3. Resting systolic blood pressure ≥160 mmHg or <90 mmHg, diastolic ≥100 mmHg pre-surgery .
   4. Intraoperative circulatory instability (e.g., hypotension, bradycardia) assessed as high-risk for trial continuation .

4. Respiratory disorders/history:

   1. Bronchial asthma, high-risk respiratory depression conditions (e.g., severe COPD ≥GOLD 3, sleep apnea syndrome) .
   2. Preoperative SpO2 <93% (room air) or intraoperative respiratory depression/ventilatory dysfunction deemed unsafe .

5. Paralytic ileus, biliary/pancreatic diseases within 12 months before screening .

6. Major surgery within 3 months prior to screening.

7. Acute/chronic non-surgical pain interfering with postoperative pain assessment .

8. Preoperative anemia: Hemoglobin <70 g/L or hematocrit <25% .

9. High bleeding risk:

   1. Congenital bleeding disorders (e.g., hemophilia) .
   2. Platelet count <0.75×LLN, PT >ULN+3s, or APTT >ULN+10s .

10. Organ dysfunction:

    1. Albumin <35 g/L (untreated) .
    2. Liver/kidney function abnormalities: TBIL/ALT/AST/ALP ≥1.5×ULN ; Creatinine ≥1.5×ULN or clinically significant renal impairment; Recent dialysis (within 28 days) .

11. Random blood glucose ≥11.1 mmol/L during screening (preoperative) .

12. Participation in other clinical trials with active treatment within 3 months before surgery .

13. Other conditions deemed unsuitable by the investigator for safety or protocol compliance.