A Clinical Trial Evaluating the Efficacy, Safety, and Pharmacokinetic Profile of TRD303 for Postoperative Analgesia After Abdominal Surgery in China.

Central South University

Status and phase: Invitation-only; Phase 3

Conditions: Pain After Abdominal Surgery

Treatments: Drug: Ropivacaine hydrochloride; Drug: TRD303 solution; Drug: 0.9 % sodium chloride

Study type: Interventional

Funder types: Other

Identifiers

NCT07353307

TRD303-Ⅲ -02

Details and patient eligibility

About

A multicenter, randomized, double-blind, placebo-positive, parallel-controlled, phase Ⅲ clinical trial of the efficacy, safety and pharmacokinetics of TRD303 solution for postoperative analgesia in patients undergoing abdominal surgery was conducted. The primary objective was to evaluate the efficacy of TRD303 solution for postoperative analgesia after abdominal surgery. The secondary objective was to evaluate the safety and pharmacokinetic profile of TRD303 solution for postoperative analgesia after abdominal surgery.

Enrollment: 333 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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 ≤80 years old, regardless of gender; 18.0kg/m2≤BMI≤30.0kg/m2, ≥50.0kg for men and ≥45.0kg for women;

4. American Society of Anesthesiologists (ASA) grade I-II (Appendix 1); (5) Elective abdominal surgery under general anesthesia, including laparoscopic or open surgery, and the length of the main incision is expected to be between 7±2cm (including the boundary value at both ends); 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. Those who are known to have allergies or contraindications to ropivacaine or other amide local anesthetics, inactive ingredients of the investigational drug, or other drugs that may be used during the trial, and who are judged by the investigator to be unsuitable for the trial;
2. Use of the following drugs for less than 5 half-lives before randomization (according to the actual drug instructions, the half-life is unknown, or eluted according to 48 hours), including but not limited to: Class III antiarrhythmic drugs, glucocorticoids (systemic), anticonvulsants, sedative-hypnotic drugs, anxiolytic drugs, antidepressant drugs, CYP1A2 enzyme inhibitor, sedative drugs (except those used according to the protocol), analgesic drugs (except those used according to the protocol), the specific types refer to the list of prohibited drugs; Use of Chinese herbal medicine with definite analgesic effect assessed by investigators within 7 days before randomization;
3. Participants who planned to use hyperthermic perfusion, intraperitoneal chemotherapy, physical therapy, or other concomitant therapies during the treatment period that the investigator judged might affect postoperative pain;
4. patients who underwent abdominal surgery within 1 year before signing ICF;
5. patients who planned to undergo surgery at other sites during the study period;
6. Combined with other pain conditions that may confound the evaluation of postoperative pain according to the investigator;
7. Participants with a history of congenital or idiopathic methemoglobinemia or glucose-6-phosphate dehydrogenase deficiency;
8. Previous and/or family history of malignant hyperthermia;
9. Participants with poorly controlled blood pressure during screening (systolic blood pressure ≥160mmHg or ≤90 mmHg while sitting during screening, and/or diastolic blood pressure ≥100 mmHg or ≤60mmHg during screening, excluding abnormal blood pressure during anesthesia), whose abnormalities were judged by the investigator to be clinically significant and increase perioperative risk;
10. Heart rate < 50 beats/min or heart rate > 100 beats/min during screening (excluding abnormal heart rate during anesthesia), and the abnormal heart rate was judged by the investigator to be clinically significant; QTcF > 450ms in men and > 470ms in women [QTcF=QT/ (RR^0.33)]; Or a history of severe arrhythmias such as atrioventricular block of degree II or higher, or cardiac insufficiency;
11. Patients with severe liver, kidney, cardiovascular, cerebrovascular, or metabolic diseases judged by the investigator to be unsuitable for the trial;
12. Patients with advanced malignant tumors who were judged by the investigators to be not suitable for participating in the trial;
13. Patients with a history of mental diseases (such as schizophrenia, depression, etc.), dementia, migraine, or epilepsy, who were judged by the investigator to be unfit for the trial;
14. Patients with skin infection, ulceration or scar constitution around the incision, judged by the investigator to be not suitable for the trial;
15. Participants with a history of psychoactive and narcotic drug abuse, drug use, and heavy drinking (i.e., drinking an average of more than 2 units of alcohol per day (1 unit =360mL of beer or 45mL of 40% liquor or 150 ml of wine) in the year before randomization;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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333 participants in 3 patient groups, including a placebo group

TRD303 group

Experimental group

Description:

Before the surgical incision was closed, TRD303 solution was applied to the incision wound.

Treatment:

Drug: TRD303 solution

Positive control group

Active Comparator group

Description:

Before the surgical incision was closed, 0.5% ropivacaine hydrochloride was injected into the incision wound

Treatment:

Drug: Ropivacaine hydrochloride

Placebo control group

Placebo Comparator group

Description:

Before the surgical incision was closed, the incision wound was infiltrated with 0.9% sodium chloride injection

Treatment:

Drug: 0.9 % sodium chloride