A Clinical Study to Evaluate Efficacy and Safety of HSK21542 for Postoperative Analgesia of Subjects Undergoing Elective Laparoscopic Surgery Under General Anesthesia

A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HSK21542 Injection for Postoperative Analgesia of Subjects Undergoing Elective Laparoscopic Surgery Under General Anesthesia

This study is a multi-center, randomized, double-blind, placebo-controlled study. A total of 276 subjects undergoing elective laparoscopic surgery under general anesthesia are planned to be enrolled and randomized into 2 groups, i.e., the HSK21542 group (138 subjects) and the placebo group (138 subjects).

Study Overview

• Status: Completed
• Conditions: Postoperative Analgesia
• Intervention / Treatment: Drug: Placebo; Drug: HSK21542

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 ≤ age ≤ 70 years old, with no gender requirement;
2. American Society of Anesthesiologists (ASA) Class I-II;
3. BMI ≥ 18 kg/m2 and ≤ 40 kg/m2;
4. Subjects undergoing elective laparoscopic surgery under general anesthesia with an expected surgery duration of 1-5 h (inclusive);
5. Agree to participate in this trial and voluntarily sign the informed consent form;

Exclusion Criteria:

1. With a history of allergy to opioids, such as urticaria, or allergic to intraoperative anesthetics as prescribed in the protocol;

2. Patients with history or evidence of any of the following diseases prior to screening:

   1. History of cardiovascular diseases: uncontrolled hypertension (systolic blood pressure [SBP] ≥ 170 mmHg and/or diastolic blood pressure [DBP] ≥ 105 mmHg without treatment, or SBP > 160 mmHg and/or DBP > 100 mmHg despite antihypertensive treatment), aneurysm, severe arrhythmia, heart failure, Adams-stokes syndrome, New York Heart Association (NYHA) Class ≥ III, severe superior vena cava syndrome, pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medical treatment, II-III degree atrioventricular block (excluding patients with pacemakers);
   2. History of respiratory system disorders: severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe airway stenosis, throat mass, history of tracheoesophageal fistula or airway tear, severe respiratory infection within 2 weeks prior to screening;
   3. History of neurological and psychiatric disorders: craniocerebral injury, convulsions, intracranial hypertension, cerebral aneurysms, history of cerebrovascular accidents; schizophrenia, mania, insanity, long-term use of psychotropic drugs, and history of cognitive dysfunction; history of depression, anxiety, and epilepsy, etc.;
   4. Have undergone any major surgery within 3 months prior to screening, which may affect postoperative pain assessment as judged by the investigator;

3. In receipt of any one of the following medications or treatments at screening:

   1. A time between the last use of opioid and non-opioid (such as paracetamol, aspirin [daily dose > 100 mg], indometacin, diclofenac, parecoxib sodium, and other non-steroidal anti-inflammatory drugs) analgesics and randomization of shorter than 5 half-lives of the drug or the duration of response (whichever is longer);
   2. Longer than 10 days of continuous use of opioid analgesics for any reason within 3 months prior to screening;
   3. Use of drugs with unknown half-life that affect the analgesic effect within 14 days before randomization, or the last use of drugs that affect the analgesic effect is within 5 half-lives (as per the packaging insert of the drug) apart from randomization, such drugs include but are not limited to: sedative-hypnotics (benzodiazepines [triazolam, diazepam, midazolam, etc.], non-benzodiazepines [zolpidem, zopiclone, zaleplon, etc.]), sedative anesthetics (sevoflurane, anesthetic ether, nitrous oxide, thiopental sodium, ketamine, etomidate, etc.), glucocorticoids (dexamethasone hydrochloride, methylprednisolone, etc.), antiepileptics (carbamazepine, sodium valproate, etc.), anxiolytics (chlordiazepoxide, diazepam, etc.), antidepressants (imipramine, amitriptyline, etc.), and Chinese herbal medicines or Chinese patent medicines with analgesic and sedative effects;
   4. Expected to receive any anti-tumor drug or therapy from 14 days prior to randomization to the end of the follow-up period, including but not limited to chemotherapy drugs, targeted drugs, and Chinese herbal medicines;
   5. A time between randomization and the last use of diuretics and compound drugs containing diuretics of shorter than 5 half-lives of the drug or the duration of response (whichever is longer);

4. The laboratory parameters measured at screening period reach one of the following criteria:

   1. WBC < 3.0 × 109/L;
   2. Platelet count < 80 × 109/L;
   3. Hemoglobin < 70 g/L;
   4. Prothrombin time > 1.5 × ULN;
   5. Activated partial thromboplastin time > 1.5 × ULN;
   6. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 × ULN;
   7. Total bilirubin > 1.5 × ULN;
   8. Blood creatinine > 1.5 × ULN;
   9. Fasting blood glucose ≥ 11.1 mmol/L;
5. Positive for hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening;
6. History of medication or drug abuse and/or alcohol abuse within 3 months prior to screening (alcohol abuse is defined as an average of > 2 units of alcohol consumed per day [1 unit = 360 mL of beer with 5% alcohol, 45 mL of liquor with 40% alcohol, or 150 mL of wine]);
7. History of blood donation or blood loss of ≥ 400 mL within 3 months prior to screening;
8. Have participated in other clinical trials within 3 months prior to screening (defined as having received investigational product or placebo);
9. Pregnant or breastfeeding females; women of child-bearing potential or men who are unwilling to use contraception during the trial; or subjects who are planning pregnancy within 3 months after the completion of the trial (including male subjects);
10. Subject judged by the investigator to have any other factors unsuitable for involvement in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo; Placebo
Experimental: HSK21542	Drug: HSK21542; HSK21542：1 µg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Differences (SPID)	The time-weighted SPID at rest within 0-24 h after the first postoperative administration in each group	Frome administration until 24 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Differences (SPID)	The time-weighted SPID at rest within 0-12 h after the first postoperative administration in each group	Frome administration until 12 hours after administration
Use of remedial analgesics	Cumulative used amount of remedial analgesics (morphine injection, mg) within 0-12 h or 0-24 h after the first postoperative administration in each group, percentage of subjects not using remedial analgesics, and start time of remedial analgesic use	Frome administration until 24 hours after administration
Pain Intensity Differences（PID）	The PID at rest at each scoring time point after the first postoperative administration in each group	Frome administration until 24 hours after administration
The proportion of subjects with a NRS of ≤ 3	The ratio of subjects with NRS score ≤ 3 at 12 h or 24 h after the first postoperative administration in each group	Frome administration until 24 hours after administration
The incidence and severity of AEs	Adverse event/serious adverse event	from signing the informed consent form to the follow-up period (D8 ± 1 postoperative).
Duration of analgesia	The duration of analgesia after the first postoperative administration in each group	Frome administration until 24 hours after administration
Satisfaction scores on postoperative analgesia	Subject satisfaction score and investigator satisfaction score on postoperative analgesia at 24 h after the first postoperative administration in each group	Frome administration until 24 hours after administration
Cumulative used amount and ratio of antiemetics	Cumulative used amount and ratio of antiemetics within 0-24 h after the first postoperative administration in each group	Frome administration until 24 hours after administration

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: January 31, 2021
• First Submitted That Met QC Criteria: January 31, 2021
• First Posted (Actual): February 4, 2021

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia
• Other Study ID Numbers: HSK21542-301

Drug and device information, study documents

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