Efficacy and Safety of HSK21542 in Inducing Postoperative Analgesia in Undergoing Elective Laparoscopic Surgery

NCT04424251 | Completed Phase 2

• 1 other identifier: HSK21542-201
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, two-stage phase II clinical study. The main objective is to evaluate the efficacy and safety of HSK21542 injection and explore the recommended dose and administration frequency for subsequent Phase II studies in conjunction with the pharmacodynamic (PD) and pharmacokinetic (PK) characteristics.

Conditions

Analgesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Sum of Pain Intensity Differences (SPID)

  Frome administration until 24 hours after administration

• Use of remedial analgesics

  Frome administration until 24 hours after administration

• Pain Intensity Differences（PID）

  Frome administration until 24 hours after administration

• The proportion of subjects with a NRS of ≤ 3

  Frome administration until 24 hours after administration

• Duration of analgesia

  Frome administration until 24 hours after administration

Study Arms (7)

stage I：HSK21542 0.4 μg/kg

EXPERIMENTAL

Preoperative:0.4 μg/kg Postoperative:0.2 μg/kg； intravenous injection

Drug: Experimental: stage I：HSK21542 0.4 μg/kg

stage I：HSK21542 1 μg/kg

EXPERIMENTAL

Preoperative:1 μg/kg Postoperative:0.5 μg/kg；intravenous injection

Drug: Experimental: stage I：HSK21542 1 μg/kg

stage I：HSK21542 0.5μg/kg

EXPERIMENTAL

Postoperative: 0.5μg/kg；intravenous injection

Drug: Experimental: stage I：HSK21542 0.5μg/kg

stage I：HSK21542 1μg/kg

EXPERIMENTAL

Postoperative: 1μg/kg；intravenous injection

Drug: Experimental: stage I：HSK21542 1μg/kg

stage II：HSK21542 0.5μg/kg

EXPERIMENTAL

Postoperative: 0.5μg/kg；intravenous injection

Drug: Experimental: stage II：HSK21542 0.5μg/kg

stage II：HSK21542 1μg/kg

EXPERIMENTAL

Postoperative: 1μg/kg；intravenous injection

Drug: Experimental: stage II：HSK21542 1μg/kg

Postoperative: Placebo

PLACEBO COMPARATOR

Placebo；intravenous injection

Drug: Placebo

Interventions

Experimental: stage I：HSK21542 0.4 μg/kg DRUG

Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations

stage I：HSK21542 0.4 μg/kg

Experimental: stage I：HSK21542 1 μg/kg DRUG

Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations

stage I：HSK21542 1 μg/kg

Experimental: stage I：HSK21542 0.5μg/kg DRUG

once each at 0, 8, and 16 h postoperative, for a total of 3 administrations

stage I：HSK21542 0.5μg/kg

Experimental: stage I：HSK21542 1μg/kg DRUG

once each at 0, 8, and 16 h postoperative, for a total of 3 administrations

stage I：HSK21542 1μg/kg

Experimental: stage II：HSK21542 0.5μg/kg DRUG

once each at 0, 8, and 16 h postoperative, for a total of 3 administrations

stage II：HSK21542 0.5μg/kg

Experimental: stage II：HSK21542 1μg/kg DRUG

once each at 0, 8, and 16 h postoperative, for a total of 3 administrations

stage II：HSK21542 1μg/kg

Placebo DRUG

once each at 0, 8, and 16 h postoperative, for a total of 3 administrations

Postoperative: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• History of allergy to opioids, such as urticaria, or allergic to the intraoperative anesthetics prescribed in the protocol;
• History or evidence of any one of the following diseases prior to screening:
• History of cardiovascular diseases: Uncontrolled hypertension (systolic blood pressure \[SBP\] ≥ 170 mmHg and/or diastolic blood pressure \[DBP\] ≥ 105 without antihypertensive 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 caval syndrome, pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction in the last 6 months before screening, history of tachycardia/bradycardia requiring medication, and II-III degree atrioventricular block (excluding patients with pacemakers);
• History of respiratory disorder: Severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe bronchostenosis, throat mass, history of (bronchial) tracheoesophageal fistula or airway tear, and severe respiratory tract infection in the last 2 weeks before screening;
• History of disorders in the nervous and psychiatric system: History of craniocerebral injury, possible convulsions, intracranial hypertension, cerebral aneurysms, and history of cerebrovascular accidents; history of schizophrenia, mania, mental aberration, long-term use of psychotropic drugs, and cognitive disorder; history of depression, anxiety, and epilepsy, etc.;
• Underwent major surgery within 3 months before screening and was judged by the investigator to have potential effect on the postoperative pain evaluation;
• Any of the following airway management risks during screening:
• Acute asthma attacks;
• Sleep apnea syndrome;
• History or family history of malignant hyperthermia;
• History of failed tracheal intubation;
• Difficult airway (modified Mallampati score ≥ III) as determined by the investigator;
• In receipt of any of the following drugs or therapies during the screening period:
• The time between randomization and the last dose of opioid or non-opioid (such as acetaminophen, aspirin \[daily dose of \> 100 mg\], indomethacin, diclofenac, parecoxib sodium and other non-steroidal anti-inflammatory drugs) analgesics is shorter than 5 half-lives of the drug or the duration of drug efficacy (whichever is longer);
• Continuous use of opioid analgesics for more than 10 days for any reason within 3 months before screening;

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, China

Location

Related Publications (1)

• Zhong Y, Wang H, Yan M, Yang M, Zhang J, Nan L, Wang Z, Yang J, Wu J, Guo Q, Hu X, Xu H, Xu Q, Wang D. Efficacy and safety of peripherally-restricted kappa-opioid receptor agonist-HSK21542 for postoperative analgesia in patients undergoing laparoscopic abdominal surgery: a randomized, placebo-controlled phase 2 trial. Front Med (Lausanne). 2025 Jul 24;12:1604790. doi: 10.3389/fmed.2025.1604790. eCollection 2025.

  PMID: 40776930 DERIVED

MeSH Terms

Conditions

Agnosia

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 9, 2020
• Study Start: July 2, 2020
• Primary Completion: December 7, 2020
• Study Completion: January 5, 2021
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

CN (1)