Phase II Clinical Study of the Efficacy and Safety of HSK55718 in the Treatment of Abdominal Postoperative Pain

To Evaluate the Efficacy and Safety of HSK55718 for Injection in Patients With Abdominal Postoperative Pain: a Multicenter, Randomized, Double-blind, Placebo/Positive Control Phase II Clinical Trial.

A multicenter, randomized, double-blind, placebo-controlled, and positive-controlled phase II clinical trial was conducted to evaluate the efficacy and safety of HSK55718 injection for postoperative analgesia in patients undergoing abdominal surgery. The primary objective was to evaluate the efficacy of HSK55718 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain After Abdominal Surgery
• Intervention / Treatment: Drug: Low dose HSK55718; Drug: Medium Dose HSK55718; Drug: High dose HSK55718; Drug: Morphine; Drug: Normal saline solution

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Saiying Wang, PhD; Phone Number: +86073188618152; Email: zwyhyll@163.com

Study Locations

• China
  • Sichuan, China
    • Sichuan Provincial People's Hospital
  • Hunan
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University, Changsha, hunan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fully understand, voluntarily participate in this study and sign the informed consent;
2. Age ≥18 years old, both sexes;
3. Undergo elective abdominal surgery (open or laparoscopic) with a (estimated) duration of ≥1 hour under general anesthesia;
4. 18.0 kg/m2≤ body mass index (BMI) ≤30.0 kg/m2
5. American Society of Anesthesiologists (ASA) grade ⅰ-ⅱ;
6. NRS≥4 in the resting state at any time within 4 hours after the end of surgery;
7. Be able to comply with the follow-up schedule and other program requirements;
8. Participants agreed to use highly effective contraception for the entire duration of the study, from the time they signed the ICF until 3 months after the last dose of the investigational product was administered.

Exclusion Criteria:

1. Disease status

1. History of vestibular dysfunction or dizziness, nausea, retching or vomiting within 1 week before screening;
2. Cardiovascular history: severe superior vena cava obstruction syndrome, severe pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, or severe arrhythmia such as atrioventricular block of degree Ⅱ or above, or history of NYHA class II or above;
3. Respiratory history: history of severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe airway stenosis, throat mass, tracheoesophageal fistula or airway tear, and severe respiratory infection within the last 2 weeks before screening;
4. History of nervous and mental system: history of craniocerebral injury, convulsion, intracranial hypertension, cerebral aneurysm, cerebrovascular accident, ischemic stroke or transient ischemic attack (TIA); History of schizophrenia, mania, psychosis, long-term use of psychotropic drugs, cognitive dysfunction, etc. Depression, anxiety, epilepsy history, etc.
5. cancer participants with advanced cancer or extensive metastases; 2. Laboratory tests during screening meet any of the following criteria:

(1) Blood routine: white blood cell count < 3.0×109/L; Platelet count < 80×109/L; Hemoglobin < 70 g/L; (2) Coagulation function: prothrombin time (PT) prolongation exceeded the upper limit of normal value for 3 seconds; Activated partial thromboplastin time (APTT) prolonged more than 10 seconds; (3) Liver and kidney function: alanine aminotransferase and/or aspartate aminotransferase > 2×ULN; Total bilirubin > 2×ULN; Serum creatinine > 1.5×ULN; (4) Fasting blood glucose ≥11.1 mmol/L; (5) Participants who did not receive regular antihypertensive treatment or whose blood pressure was poorly controlled (systolic blood pressure ≥160mmHg or ≤90mmHg at screening, and/or diastolic blood pressure ≥100mmHg or ≤60mmHg at screening, excluding abnormalities during anesthesia from admission to PACU and during recovery from anesthesia); (6) QTc >450ms in men and >470ms in women (QTc was calculated with Fridericia's formula); (7) Transcutaneous oxygen saturation (SpO2) <90% during screening (excluding abnormal anesthesia from admission to PACU and anesthesia recovery period); (8) Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody were positive during the screening period; 3. Medication use

1. Patients with a history of severe drug allergy, or other drugs that may be used during the trial, such as anesthetics propofol/sevoflurane, rocuronium, antiemetic drugs, or drugs and their excipients;
2. Taking opioid analgesics for any reason for more than 10 consecutive days within 3 months before randomization;
3. Drugs that may affect the evaluation of efficacy if the time interval between the last administration of the drug and randomization is less than five half-lives of the drug, including but not limited to the following drugs: Selective α2-adrenoceptor agonists, opioid agonists/antagonists, non-steroidal anti-inflammatory drugs, sedative drugs, monoamine oxidase inhibitors, glucocorticoids, antiepileptic, anxiolytic, antidepressant and other antipsychotic drugs. Refer to the list of banned drugs for specific types.
4. Use of a strong inducer or inhibitor of CYP3A within 14 days or 5 half-lives before the first dose of the investigational drug, whichever is longer; 4: Others

(1) Having a history of drug abuse, drug abuse and/or alcohol abuse in the past year, with alcohol abuse defined as drinking an average of > 2 units of alcohol per day (1 unit =360mL of 5% beer or 45mL of 40% liquor or 150mL of wine); (2) Positive results of drug abuse screening during the screening period; (3) Pregnant or lactating women; (4) Had participated in other drug clinical trials (defined as receiving investigational drug or placebo) within 3 months before the screening period; (5) Any sensory dysfunction that may interfere with the ability to assess postoperative pain according to the investigator's judgment; (6) Painful physical conditions that may interfere with postoperative evaluation according to the investigator's judgment; (7) Participants had medical complications during the operation and were not suitable for further study according to the investigator's judgment; (8) Participants with any other factors considered by the investigator to be ineligible for the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 15mg/7.5mg GHSK55718 group; After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 15mg was given intravenously, and then 7.5mg HSK55718 injection or normal saline was given intermittently every 6 hours	Drug: Low dose HSK55718; NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 15mg was given intravenously, and then 7.5mg HSK55718 injection or normal saline was given intermittently every 6 hours
Experimental: 60mg/30mg GHSK55718 group; After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 60mg was given intravenously, and then30mg HSK55718 injection or normal saline was given intermittently every 6 hours	Drug: Medium Dose HSK55718; NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 60mg was given intravenously, and then 30mg HSK55718 injection or normal saline was given intermittently every 6 hours.
Experimental: 120mg/60mg GHSK55718 group; After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 120mg was given intravenously, and then 60mg HSK55718 injection or normal saline was given intermittently every 6 hours	Drug: High dose HSK55718; NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 120mg was given intravenously, and then 60mg HSK55718 injection or normal saline was given intermittently every 6 hours
Active Comparator: Positive control group; After the postoperative NRS pain score ≥4, morphine injection 2mg was given intravenously as the first dose, and then morphine injection 2mg was given intermittently every 6 hours	Drug: Morphine; NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, morphine injection 2mg was given intravenously as the first dose, and then morphine injection 2mg was given intermittently every 6 hours
Placebo Comparator: Placebo control group; After the postoperative NRS pain score ≥4, normal saline was administered intravenously and then intermittently every 6h	Drug: Normal saline solution; NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, normal saline solution was given intravenously as the first dose, and then normal saline solution was given intermittently every 6 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time-weighted summed pain intensity differences over 24 h (SPID0-24 h) at rest	The time-weighted summed pain intensity differences during 0-24 hours (SPID0-24 h) at rest after the first dose	From administration until 24 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the time-weighted summed pain intensity differences (SPID) at rest	The time-weighted summed pain intensity differences during 0-12h, 12-24h, 24-48h, and 0-48h (SPID0-12h、SPID12-24h、SPID24-48h、SPID0-48h) at rest after the first dose	From administration until 12 hours, 48 hours after administration, from 12 hours to 24 hours and 24 hours to 48 hours after administration.
Pain intensity differences (PID)	The rest pain intensity difference (PID) was calculated at each scoring time point after the first dose, and PID was the difference between the NRS score at each time point and the baseline NRS score	From administration until 48 hours after administration
The proportion of NRS pain score ≤3		From administration until 48 hours after administration
Time to onset		From administration until 12 hours after administration
Cumulative use of rescue analgesics during each period		From the time of administration to 24 hours and 48 hours after administration
Time of first sufentanil rescue analgesia		From administration until 48 hours after administration
Proportion of rescue analgesia		From administration until 48 hours after administration
Postoperative analgesia satisfaction score	At 24 hours after the end of the study, participants recalled the analgesic effect of the postoperative analgesia and rated their satisfaction on a scale of 0 to 10, with 0 indicating dissatisfied and 10 very satisfied.	From administration until 48 hours after administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of HSK55718	Maximum plasma concentration of HSK55718 after Administration	From administration until 48 hours after administration
Area under curve (AUC) of the plasma concentration-time during 0-∞ (AUC0-∞)	The total area under the curve (AUC0-∞) at the time of clearance of all prototype drugs from drug administration to day 7 after administration reflects drug absorption and metabolism	From the time of administration to day 7 after administration
Area under curve (AUC) of the plasma concentration-time during 0-t (t=0 to 48h)	The area under the concentration-time curve (AUC0-t, t= 0-48h) from the beginning of administration to time t, and the absorption and metabolism of the reaction drug over time	From administration until time t (t=0 to 48hours after administration)

Collaborators and Investigators

• Sponsor: Yingyong Zhou,MD,PhD

Study record dates

Study Major Dates

• Study Start (Estimated): March 25, 2026
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Morphine; Saline Solution
• Other Study ID Numbers: HSK55718-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No