<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04424251</url>
  </required_header>
  <id_info>
    <org_study_id>HSK21542-201</org_study_id>
    <nct_id>NCT04424251</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of HSK21542 in Inducing Postoperative Analgesia in Undergoing Elective Laparoscopic Surgery</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Two-stage Phase II Study Evaluating the Efficacy and Safety of HSK21542 in Inducing Postoperative Analgesia in Subjects Undergoing Elective Laparoscopic Surgery Under General Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Haisco Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Haisco Pharmaceutical Group Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, randomized, double-blind, placebo-controlled, two-stage phase II&#xD;
      clinical study. The main objective is to evaluate the efficacy and safety of HSK21542&#xD;
      injection and explore the recommended dose and administration frequency for subsequent Phase&#xD;
      II studies in conjunction with the pharmacodynamic (PD) and pharmacokinetic (PK)&#xD;
      characteristics.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2020</start_date>
  <completion_date type="Actual">April 28, 2021</completion_date>
  <primary_completion_date type="Actual">January 5, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence and severity of AEs</measure>
    <time_frame>From screening up to 4 weeks</time_frame>
    <description>Adverse event/serious adverse event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs: Systolic and Diastolic Blood Pressure</measure>
    <time_frame>From screening up to 4 weeks</time_frame>
    <description>Vital signs (Systolic and Diastolic Blood Pressure) will be collected in subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sum of Pain Intensity Differences (SPID)</measure>
    <time_frame>Frome administration until 24 hours after administration</time_frame>
    <description>The time-weighted sum of pain intensity differences of the rest pain in each group within 0-12 h and 0-24 h after the first postoperative dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of remedial analgesics</measure>
    <time_frame>Frome administration until 24 hours after administration</time_frame>
    <description>Cumulative dose of remedial analgesics (mg of morphine injection) in each group within 0-12 h and 0-24 h after the first postoperative dose, the percentage of subjects in each group who have not used remedial analgesics, and the time to start using remedial analgesics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of subjects with a NRS of ≤ 3</measure>
    <time_frame>Frome administration until 24 hours after administration</time_frame>
    <description>The proportion of subjects in each group with a resting pain NRS of ≤ 3 at 12 h and 24 h after the first postoperative dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The plasma concentration</measure>
    <time_frame>-30 minutes before administration until 24 hours after administration</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Analgesia</condition>
  <arm_group>
    <arm_group_label>stage I：HSK21542 0.4 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Preoperative:0.4 μg/kg Postoperative:0.2 μg/kg； intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage I：HSK21542 1 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Preoperative:1 μg/kg Postoperative:0.5 μg/kg；intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage I：HSK21542 0.5μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Postoperative: 0.5μg/kg；intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage I：HSK21542 1μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Postoperative: 1μg/kg；intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage II：HSK21542 0.5μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Postoperative: 0.5μg/kg；intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stage II：HSK21542 1μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Postoperative: 1μg/kg；intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Postoperative: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo；intravenous injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage I：HSK21542 0.4 μg/kg</intervention_name>
    <description>Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations</description>
    <arm_group_label>stage I：HSK21542 0.4 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage I：HSK21542 1 μg/kg</intervention_name>
    <description>Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations</description>
    <arm_group_label>stage I：HSK21542 1 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage I：HSK21542 0.5μg/kg</intervention_name>
    <description>once each at 0, 8, and 16 h postoperative, for a total of 3 administrations</description>
    <arm_group_label>stage I：HSK21542 0.5μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage I：HSK21542 1μg/kg</intervention_name>
    <description>once each at 0, 8, and 16 h postoperative, for a total of 3 administrations</description>
    <arm_group_label>stage I：HSK21542 1μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage II：HSK21542 0.5μg/kg</intervention_name>
    <description>once each at 0, 8, and 16 h postoperative, for a total of 3 administrations</description>
    <arm_group_label>stage II：HSK21542 0.5μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: stage II：HSK21542 1μg/kg</intervention_name>
    <description>once each at 0, 8, and 16 h postoperative, for a total of 3 administrations</description>
    <arm_group_label>stage II：HSK21542 1μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>once each at 0, 8, and 16 h postoperative, for a total of 3 administrations</description>
    <arm_group_label>Postoperative: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 ≤ age ≤ 65 years old, with no gender requirement&#xD;
&#xD;
          2. American Society of Anesthesiologists (ASA) Class I-II&#xD;
&#xD;
          3. 18 kg/m^2 ≤ BMI ≤ 30 kg/m^2&#xD;
&#xD;
          4. Subjects undergoing elective laparoscopic surgery under general anesthesia with an&#xD;
             expected surgery duration of 1-5 h (inclusive)&#xD;
&#xD;
          5. Agree to participate in this trial and voluntarily sign the informed consent form;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of allergy to opioids, such as urticaria, or allergic to the intraoperative&#xD;
             anesthetics prescribed in the protocol;&#xD;
&#xD;
          2. History or evidence of any one of the following diseases prior to screening:&#xD;
&#xD;
               1. History of cardiovascular diseases: Uncontrolled hypertension (systolic blood&#xD;
                  pressure [SBP] ≥ 170 mmHg and/or diastolic blood pressure [DBP] ≥ 105 without&#xD;
                  antihypertensive treatment, or SBP &gt; 160 mmHg and/or DBP &gt; 100 mmHg despite&#xD;
                  antihypertensive treatment), aneurysm, severe arrhythmia, heart failure,&#xD;
                  Adams-Stokes syndrome, New York Heart Association (NYHA) Class ≥ III, severe&#xD;
                  superior vena caval syndrome, pericardial effusion, acute myocardial ischemia,&#xD;
                  unstable angina, myocardial infarction in the last 6 months before screening,&#xD;
                  history of tachycardia/bradycardia requiring medication, and II-III degree&#xD;
                  atrioventricular block (excluding patients with pacemakers);&#xD;
&#xD;
               2. History of respiratory disorder: Severe chronic obstructive pulmonary disease,&#xD;
                  acute exacerbation of chronic obstructive pulmonary disease, severe&#xD;
                  bronchostenosis, throat mass, history of (bronchial) tracheoesophageal fistula or&#xD;
                  airway tear, and severe respiratory tract infection in the last 2 weeks before&#xD;
                  screening;&#xD;
&#xD;
               3. History of disorders in the nervous and psychiatric system: History of&#xD;
                  craniocerebral injury, possible convulsions, intracranial hypertension, cerebral&#xD;
                  aneurysms, and history of cerebrovascular accidents; history of schizophrenia,&#xD;
                  mania, mental aberration, long-term use of psychotropic drugs, and cognitive&#xD;
                  disorder; history of depression, anxiety, and epilepsy, etc.;&#xD;
&#xD;
               4. Underwent major surgery within 3 months before screening and was judged by the&#xD;
                  investigator to have potential effect on the postoperative pain evaluation;&#xD;
&#xD;
          3. Any of the following airway management risks during screening:&#xD;
&#xD;
               1. Acute asthma attacks;&#xD;
&#xD;
               2. Sleep apnea syndrome;&#xD;
&#xD;
               3. History or family history of malignant hyperthermia;&#xD;
&#xD;
               4. History of failed tracheal intubation;&#xD;
&#xD;
               5. Difficult airway (modified Mallampati score ≥ III) as determined by the&#xD;
                  investigator;&#xD;
&#xD;
          4. In receipt of any of the following drugs or therapies during the screening period:&#xD;
&#xD;
               1. The time between randomization and the last dose of opioid or non-opioid (such as&#xD;
                  acetaminophen, aspirin [daily dose of &gt; 100 mg], indomethacin, diclofenac,&#xD;
                  parecoxib sodium and other non-steroidal anti-inflammatory drugs) analgesics is&#xD;
                  shorter than 5 half-lives of the drug or the duration of drug efficacy (whichever&#xD;
                  is longer);&#xD;
&#xD;
               2. Continuous use of opioid analgesics for more than 10 days for any reason within 3&#xD;
                  months before screening;&#xD;
&#xD;
               3. Use of drugs that affect the analgesic effect within 14 days before&#xD;
                  randomization, including but not limited to: Sedative hypnotics (benzodiazepines&#xD;
                  [triazolam, diazepam, midazolam, etc.], non-benzodiazepines [zolpidem, zopiclone,&#xD;
                  zaleplon, etc.]), sedative anesthetics (sevoflurane, anesthesia ether, nitrous&#xD;
                  oxide, thiopental, ketamine, etomidate, etc.), glucocorticoids (dexamethasone&#xD;
                  hydrochloride , methylprednisolone, etc.), anti-epilepsy drugs (carbamazepine,&#xD;
                  sodium valproate, etc.), anxiolytics (carbamazepine, diazepam, etc.),&#xD;
                  antidepressants (imipramine, amitriptyline, etc.), and Chinese herbal medicines&#xD;
                  or Chinese patent medicines with analgesic and sedative effects;&#xD;
&#xD;
               4. Expected to receive anti-tumor drugs and treatments during the period from 14&#xD;
                  days before randomization to the end of the follow-up period, including but not&#xD;
                  limited to chemotherapeutic drugs, targeted drugs, and Chinese herbal medicines.&#xD;
&#xD;
               5. The time between randomization and the last use of diuretics and compound drugs&#xD;
                  containing diuretic components is shorter than 5 half-lives of the drug or the&#xD;
                  duration of drug efficacy (whichever is longer);&#xD;
&#xD;
          5. Laboratory test parameters meet one of the following criteria in the screening period&#xD;
             and is confirmed by retests:&#xD;
&#xD;
               1. White blood cell count &lt; 3.0 x 10^9/L;&#xD;
&#xD;
               2. Platelet count &lt; 80 x 10^9/L;&#xD;
&#xD;
               3. Hemoglobin &lt; 80 g/L;&#xD;
&#xD;
               4. Prothrombin time &gt; 1.5 x ULN;&#xD;
&#xD;
               5. Activated partial thromboplastin time &gt; 1.5 x ULN;&#xD;
&#xD;
               6. Alanine aminotransferase and/or aspartate aminotransferase &gt; 2 x ULN;&#xD;
&#xD;
               7. Total bilirubin &gt; 1.5 x ULN;&#xD;
&#xD;
               8. Blood creatinine &gt; 1.5 x ULN;&#xD;
&#xD;
               9. Fasting blood glucose ≥ 11.1 mmol/L;&#xD;
&#xD;
          6. Without oxygen supplement during the screening period, the pulse oxygen saturation is&#xD;
             &lt; 92%;&#xD;
&#xD;
          7. During the screening period, the virological examination for hepatitis B surface&#xD;
             antigen (HBsAg), hepatitis C antibody (HCVAb), treponema pallidum antibody, or human&#xD;
             immunodeficiency virus (HIV) antibody is positive;&#xD;
&#xD;
          8. History of drug abuse, narcotics use and/or alcohol abuse within 3 months before&#xD;
             screening. Alcohol abuse is defined as &gt; 2 units of alcohol consumption per day (1&#xD;
             unit = 360 mL of beer containing 5% alcohol, 45 mL of liquor containing 40% alcohol,&#xD;
             or 150 mL of wine);&#xD;
&#xD;
          9. Donated or lost ≥ 400 mL of blood within 3 months before screening;&#xD;
&#xD;
         10. Participated in any drug clinical trials within 3 months before screening (defined as&#xD;
             the administration of the investigational product or placebo);&#xD;
&#xD;
         11. Women who are pregnant or breastfeeding; fertile women or men who are unwilling to use&#xD;
             contraception during the trial; subjects who are planning pregnancy within 3 month&#xD;
             after the completion of the trial (including male subjects);&#xD;
&#xD;
         12. Subjects determined by the investigator to be unsuitable for participating in this&#xD;
             clinical study for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Second Affiliated Hospital of Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Agnosia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04424251
org study id: HSK21542-201
nct id: NCT04424251
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: The incidence and severity of AEs
time frame: From screening up to 4 weeks
description: Adverse event/serious adverse event
measure: Vital signs: Systolic and Diastolic Blood Pressure
time frame: From screening up to 4 weeks
description: Vital signs (Systolic and Diastolic Blood Pressure) will be collected in subjects.
measure: Sum of Pain Intensity Differences (SPID)
time frame: Frome administration until 24 hours after administration
description: The time-weighted sum of pain intensity differences of the rest pain in each group within 0-12 h and 0-24 h after the first postoperative dose
measure: Use of remedial analgesics
time frame: Frome administration until 24 hours after administration
description: Cumulative dose of remedial analgesics (mg of morphine injection) in each group within 0-12 h and 0-24 h after the first postoperative dose, the percentage of subjects in each group who have not used remedial analgesics, and the time to start using remedial analgesics
measure: The proportion of subjects with a NRS of ≤ 3
time frame: Frome administration until 24 hours after administration
description: The proportion of subjects in each group with a resting pain NRS of ≤ 3 at 12 h and 24 h after the first postoperative dose
measure: The plasma concentration
time frame: -30 minutes before administration until 24 hours after administration
arm group label: stage I：HSK21542 0.4 μg/kg
arm group type: Experimental
description: Preoperative:0.4 μg/kg Postoperative:0.2 μg/kg； intravenous injection
arm group label: stage I：HSK21542 1 μg/kg
arm group type: Experimental
description: Preoperative:1 μg/kg Postoperative:0.5 μg/kg；intravenous injection
arm group label: stage I：HSK21542 0.5μg/kg
arm group type: Experimental
description: Postoperative: 0.5μg/kg；intravenous injection
arm group label: stage I：HSK21542 1μg/kg
arm group type: Experimental
description: Postoperative: 1μg/kg；intravenous injection
arm group label: stage II：HSK21542 0.5μg/kg
arm group type: Experimental
description: Postoperative: 0.5μg/kg；intravenous injection
arm group label: stage II：HSK21542 1μg/kg
arm group type: Experimental
description: Postoperative: 1μg/kg；intravenous injection
arm group label: Postoperative: Placebo
arm group type: Placebo Comparator
description: Placebo；intravenous injection
intervention type: Drug
intervention name: Experimental: stage I：HSK21542 0.4 μg/kg
description: Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations
arm group label: stage I：HSK21542 0.4 μg/kg
intervention type: Drug
intervention name: Experimental: stage I：HSK21542 1 μg/kg
description: Once preoperative and once each at 0, 8, and 16 h postoperative, for a total of 4 administrations
arm group label: stage I：HSK21542 1 μg/kg
intervention type: Drug
intervention name: Experimental: stage I：HSK21542 0.5μg/kg
description: once each at 0, 8, and 16 h postoperative, for a total of 3 administrations
arm group label: stage I：HSK21542 0.5μg/kg
intervention type: Drug
intervention name: Experimental: stage I：HSK21542 1μg/kg
description: once each at 0, 8, and 16 h postoperative, for a total of 3 administrations
arm group label: stage I：HSK21542 1μg/kg
intervention type: Drug
intervention name: Experimental: stage II：HSK21542 0.5μg/kg
description: once each at 0, 8, and 16 h postoperative, for a total of 3 administrations
arm group label: stage II：HSK21542 0.5μg/kg
intervention type: Drug
intervention name: Experimental: stage II：HSK21542 1μg/kg
description: once each at 0, 8, and 16 h postoperative, for a total of 3 administrations
arm group label: stage II：HSK21542 1μg/kg
intervention type: Drug
intervention name: Placebo
description: once each at 0, 8, and 16 h postoperative, for a total of 3 administrations
arm group label: Postoperative: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Agnosia