Clinical trial NCT04738357: A Clinical Study to Evaluate Efficacy and Safety of HSK21542 for Postoperative Analgesia of Subjects Undergoing Elective Laparoscopic Surgery Under General Anesthesia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Analgesia
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-04
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Sum of Pain Intensity Differences (SPID)
timeFrame: Frome administration until 24 hours after administration
Secondary outcomes:
measure: Sum of Pain Intensity Differences (SPID)
timeFrame: Frome administration until 12 hours after administration
measure: Use of remedial analgesics
timeFrame: Frome administration until 24 hours after administration
measure: Pain Intensity Differences（PID）
timeFrame: Frome administration until 24 hours after administration
measure: The proportion of subjects with a NRS of ≤ 3
timeFrame: Frome administration until 24 hours after administration
measure: Duration of analgesia
timeFrame: Frome administration until 24 hours after administration
measure: Satisfaction scores on postoperative analgesia
timeFrame: Frome administration until 24 hours after administration
measure: The incidence and severity of AEs
timeFrame: from signing the informed consent form to the follow-up period (D8 ± 1 postoperative).
measure: Cumulative used amount and ratio of antiemetics
timeFrame: Frome administration until 24 hours after administration
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Second Affiliated Hospital of Zhejiang University School of Medicine
Study officials:
References: