Postoperative Pain
Conditions
Brief summary
This is a randomized, double-blind, active drug- and placebo-controlled, dose-escalation clinical study conducted in patients scheduled to undergo abdominal surgery. It aims to evaluate the tolerability, safety, pharmacokinetics, and efficacy of SYH9089 Injection for postoperative analgesia in these patients.
Interventions
DRUGSYH9089 injection
Before the surgical incision was closed, SYH9089 injection was applied to the incision wound.
Before the surgical incision was closed, 0.5% ropivacaine hydrochloride was injected into the incision wound, and a total of 20mL was given.
Before the surgical incision was closed, the incision wound was infiltrated with 0.9% sodium chloride injection.
Sponsors
CSPC Ouyi Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This is a randomized, double-blind, parallel-group, dose-escalation study. Sixty subjects scheduled for abdominal surgery will be enrolled and equally allocated to 5 dose groups (12 subjects per group). Within each group, subjects will be randomly assigned in a 4:1:1 ratio to receive SYH9089, active comparator, or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Fully understand the purpose and significance of this study, voluntarily participate in this study, voluntarily sign the informed consent, and voluntarily abide by the process of this study; 2. 18 years old ≤ age ≤75 years old, regardless of gender; 3. 19.0kg/m2≤BMI≤28.0kg/m2, ≥50.0kg for men and ≥45.0kg for women; 4. American Society of Anesthesiologists (ASA) grade I-II; 5. Elective abdominal surgery under general anesthesia, and the anticipated surgical incision is approximately 8-10 cm (inclusive), including at least one single incision of ≥ 5 cm in length; 6. Can understand the research process and the use of various scales involved in this study, and can effectively communicate with researchers.
Exclusion criteria
* 1\. Patients with a history of hypersensitivity to the investigational drug, comparator drug, surgical anesthetics, rescue analgesic drugs, or other drugs that may be used during the trial; 2. Patients with a history of drug abuse/substance use, or those with positive results on a drug abuse screening; 3. Patients with neurological/psychiatric, respiratory, endocrine, hematologic, musculoskeletal, gastrointestinal, cardiovascular systems, or hepatic/renal diseases, judged by the investigator to be unsuitable for the trial; 4. Patients with a history of diabetes mellitus; 5. Patients with a history of myocardial infarction or unstable angina within 1 year prior to randomization; 6. Patients scheduled to undergo purely diagnostic exploratory surgery or palliative tumor resection, judged by the investigator to be unsuitable for the trial; 7. Patients with advanced malignant tumors with extensive metastasis during the screening period, judged by the investigator to be unsuitable for the trial; 8. Combined with other pain conditions that may confound the evaluation of postoperative pain according to the investigator; 9. Patients with a history of severe or refractory postoperative nausea or vomiting; 10. Use of the following drugs for less than 5 half-lives before randomization (based on the actual drug instructions; or within 7 days prior to randomization if the half-life is unclear) which, in the investigator's judgement, may affect the evaluation of analgesic efficacy. These include, but are not limited to: narcotics (opioids), local anesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), sedative-hypnotics, non-benzodiazepines, sedative anesthetics, glucocorticoids (except for topical use), antiepileptics, anxiolytics, antidepressants, as well as Chinese herbal medicines or proprietary Chinese medicines with sedative or analgesic effects; 11. Use of strong CYP1A2 inhibitors for less than 5 half-lives before randomization (e.g., atazanavir, ciprofloxacin, enoxacin, fluvoxamine, ethinylestradiol) ； 12. Subjects with abnormal findings during the screening period (prior to admission) in vital signs, physical examination, 12-lead ECG, or laboratory tests, which in the investigator's judgement make the subject unsuitable for participation in this trial, including: 1. Patientss with poorly controlled blood pressure despite medication: systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg; or systolic blood pressure \<90 mmHg; 2. 12-lead ECG: QTcF ≥450 ms for males or ≥470 ms for females, or a history of severe arrhythmias such as second-degree type II or higher atrioventricular block, or a history of cardiac insufficiency; 3. Coagulation function: PT \> ULN + 3 seconds and/or APTT \> ULN + 10 seconds; 4. Liver function: ALT and/or AST ≥ 2 × ULN; TBIL ≥ 1.5 × ULN; ALB \< 30 g/L; 5. Renal function: Cr ≥ 1.5 × ULN; 6. PLT \< 80 × 10\^9/L; 7. HGB \< 90 g/L; 8. Random blood glucose \> 11.1 mmol/L. 13. Positive for HBsAg, HCV-Ab, HIV-Ab, or TP-Ab;; 14. Female subjects with a positive pregnancy test or who are breast feeding; fertile subjects who plan to become pregnant, are unwilling or unable to use effective contraception during the trial and within 3 months after administration, or who plan to donate sperm or ova; 15. Patients with a history of drug abuse, substance use, and/or alcoholism within 6 months prior to randomization, (alcoholism is defined as alcohol consumption exceeding 14 units per week:1 unit = 360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine); 16. Patients who underwent major surgery within 3 months prior to randomization, or surgery that may significantly affect the in vivo metabolism of the investigational product or the evaluation of safety; 17. Patients with blood loss or blood donation exceeding 400 mL, or who received blood transfusion or blood products within 3 months prior to randomization; 18. Patients who participated in any clinical trial of drugs or medical devices within 3 months prior to randomization; 19. Any other conditions judged by the investigator to be unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Profile | 14 days | Participants with an Adverse Event through 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) at Rest (NRS-R) Pain Intensity Scores | 0 to 120 hours | The AUC of NRS-R during 0-6 h，0-12 h，0-24 h，0-48 h，0-72 h，0-96 h，0-120 h，24-48 h，48-72 h，24-72 h，72-96 h，and 96-120 h after administration. Pain intensity was assessed on a scale of 0 to 10, where 0=no pain and 10=worst possible pain. |
| Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) With Activity (NRS-A) Pain Intensity Scores | 0 to 120 hours | The AUC of NRS-A during 0-6 h，0-12 h，0-24 h，0-48 h，0-72 h，0-96 h，0-120 h，24-48 h，48-72 h，24-72 h，72-96 h，and 96-120 h after administration. Pain intensity was assessed on a scale of 0 to 10, where 0=no pain and 10=worst possible pain. |
| Cumulative use of rescue analgesics during each period | 0 to 120 hours | Cumulative amount of rescue analgesics used during 0-6 h，0-12 h，0-24 h，0-48 h，0-72 h，0-96 h，0-120 h，24-48 h，48-72 h，24-72 h，72-96 h，and 96-120 h after administration. |
| Proportion of participants not requiring rescue analgesia in each period | 0 to 120 hours | Proportion of participants not requiring rescue analgesia within 0-6 h，0-12 h，0-24 h，0-48 h，0-72 h，0-96 h，0-120 h，24-48 h，48-72 h，24-72 h，72-96 h，and 96-120 h after administration. |
| Proportion of participants with an NRS-A score ≤ 1 at different time points. | 0 to 120 hours | Proportion of participants with an NRS-A score ≤ 1 at 6 h, 12 h, 24 h, 48 h, 72 h, 96 h, and 120 h after administration. |
| Proportion of participants with an NRS-R score ≤ 1 at different time points. | 0 to 120 hours | Proportion of participants with an NRS-R score ≤ 1 at 6 h, 12 h, 24 h, 48 h, 72 h, 96 h, and 120 h after administration. |
| Time of first morphine rescue analgesia | 0 to 120 hours | The time from administration to the first morphine rescue analgesic treatment |
| Maximum pain score at each dressing change | 0 to 72 hours | Maximum pain score at each dressing change at 24 h, 48 h, and 72 h after administration. |
| Participant's Analgesic Satisfaction Score | 0 to 120 hours | Participant satisfaction will be assessed at 120 hours after administration. |
| Investigator Satisfaction Score | 0 to 120 hours | Investigator satisfaction will be assessed at 120 hours after administration |
Outcome results
None listed