xml: <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/NCT06007066</url>
    </required_header>
    <id_info>
      <org_study_id>HSK16149-204</org_study_id>
      <nct_id>NCT06007066</nct_id>
    </id_info>
    <brief_title>HSK16149 for Perioperative Analgesia in Orthopedic Surgery</brief_title>
    <official_title>A Multicenter, Randomized, Double-Blind, Placebo-controlled Phase II Study of The Efficacy And Safety of HSK16149 In The Treatment of Patients With Orthopedic Perioperative Analgesia</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>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will compare the effect and safety of HSK16149 with placebo on perioperative&#xD;
        analgesia in orthopedic surgery, and explore the dosage of HSK16149 capsules for orthopedic&#xD;
        analgesia during perioperative period.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study included patients who have orthopedic surgery under general anesthetic, with&#xD;
        expected operation time ≤4h.&#xD;
  &#xD;
        Subjects were given 40mg or 60mg of HSK16149 or placebo orally the night before surgery, 2h&#xD;
        before surgery, 4h and 16h after surgery, for a total of 4 times during the whole treatment&#xD;
        period.&#xD;
  &#xD;
        Subjects will receive intravenous patient-controlled analgesia (PCA) morphine for pain in the&#xD;
        immediate postoperative period. If PCA is insufficient, rescue analgesia of morphine may be&#xD;
        given I.V. as determined by the investigator.&#xD;
  &#xD;
        After the treatment period, the subjects will be followed up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">March 8, 2023</start_date>
    <completion_date type="Actual">July 5, 2023</completion_date>
    <primary_completion_date type="Actual">June 12, 2023</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>Morphine Consumption</measure>
      <time_frame>Participants received PCA pump, an average of 24 hours after surgery</time_frame>
      <description>IV Patient Controlled Analgesia (PCA) morphine for pain management in the immediate postoperative period for an average of 24 hours after surgery. If PCA is insufficient, rescue analgesia of morphine may be given I.V. as determined by the investigator.&#xD;
  Total morphine consumption = PCA morphine consumption + rescue analgesia morphine consumption.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>NRS at rest and during exercise</measure>
      <time_frame>1, 2, 6, 12, 18, and 24 hours after surgery</time_frame>
      <description>NRS:0 (no pain) to 10 (worst possible pain)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of first rescue analgesia with morphine after surgery</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse reactions associated with morphine</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The frequency of rescue analgesia with morphine</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The total number of PCA presses and the number of effective PCA presses</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily Sleep Interference Scale (DSIS)</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
      <description>Subjects review their sleep status during the past 12 hours at 8:00 a.m. on the day of surgery.&#xD;
  DSIS: 0 (not affecting sleep) to 10 (unable to sleep)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Subjects analgesic satisfaction score</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
      <description>Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Investigators analgesic satisfaction score</measure>
      <time_frame>Within 24 hours after surgery</time_frame>
      <description>Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with treatment-related adverse events(TEAE) as assessed by CTCAE v5.0.</measure>
      <time_frame>From enrollment to 72 hours after surgery</time_frame>
      <description>Number and severity of AEs, clinical laboratory abnormalities, physical examinations, 12-lead electrocardiograms (ECGs)(including QT Interval,QTc Interval and PR Interval), and vital signs.</description>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Actual">235</enrollment>
    <condition>Post-operative Pain</condition>
    <arm_group>
      <arm_group_label>Preoperative administration of HSK16149 40mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HSK16149 40mg will be administered the night before and 2h before surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Preoperative administration of HSK16149 60mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HSK16149 60mg will be administered the night before and 2h before surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Preoperative and postoperative administration of HSK16149 40mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HSK16149 40mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Preoperative and postoperative administration of HSK16149 60mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>HSK16149 60mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The placebo will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>HSK16149 capsule</intervention_name>
      <description>Subjects will be given 40mg or 60mg of HSK16149 orally.</description>
      <arm_group_label>Preoperative administration of HSK16149 40mg</arm_group_label>
      <arm_group_label>Preoperative administration of HSK16149 60mg</arm_group_label>
      <arm_group_label>Preoperative and postoperative administration of HSK16149 40mg</arm_group_label>
      <arm_group_label>Preoperative and postoperative administration of HSK16149 60mg</arm_group_label>
      <other_name>HSK16149</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Subjects will be given HSK16149 placebo orally.</description>
      <arm_group_label>placebo</arm_group_label>
      <other_name>HSK16149 placebo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female between the ages of 18 and 75 years (included);&#xD;
  &#xD;
            2. Elective orthopedic surgery under general anesthesia, expected operation time ≤4 hours&#xD;
               and postoperative morphine analgesia time ≥24 hours;&#xD;
  &#xD;
            3. 18kg/m^2≤BMI≤30 kg/m^2;&#xD;
  &#xD;
            4. American Society of Anesthesiologists (ASA) grade I and II;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Any of the following medical histories or conditions prior to screening:&#xD;
  &#xD;
                 -  Long history of chronic pain;&#xD;
  &#xD;
                 -  history of severe cardiovascular or respiratory disease;&#xD;
  &#xD;
                 -  history of neurological or psychiatric disorders;&#xD;
  &#xD;
                 -  history of acute poisoning with alcohol, hypnotics, analgesics or other drugs&#xD;
                    acting on the central nervous system;&#xD;
  &#xD;
                 -  major surgery within 3 months;&#xD;
  &#xD;
                 -  patients with high bleeding risk;&#xD;
  &#xD;
                 -  history of renal disease treated with dialysis within 28 days before surgery;&#xD;
  &#xD;
                 -  have active infection within the past 2 weeks;&#xD;
  &#xD;
            2. Use of any of the following medications or treatments:&#xD;
  &#xD;
                 -  opioid analgesics for more than 10 consecutive days within 3 months prior to&#xD;
                    screening;&#xD;
  &#xD;
                 -  other analgesics before randomization if the last dose was taken less than 5&#xD;
                    half-lives of the drug (according to the label);&#xD;
  &#xD;
            3. Abnormal laboratory tests during screening:&#xD;
  &#xD;
            4. Hypertension that is not adequately controlled by antihypertensive drugs (systolic&#xD;
               blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), or systolic blood&#xD;
               pressure ≤90 mmHg during screening;&#xD;
  &#xD;
            5. A history of drug abuse, and/or alcohol abuse in the 3 months prior to screening;&#xD;
  &#xD;
            6. Participated in another clinical trial and received IMP within 30 days prior to&#xD;
               screening;&#xD;
  &#xD;
            7. Pregnant or lactating women;&#xD;
  &#xD;
            8. Unwillingness to use reliable contraceptive methods from the time of screening until&#xD;
               28 days after the last dose of IMP;&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Dongguan People's Hospital</name>
        <address>
          <city>Dongguan</city>
          <state>Guangdong</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Foshan Fuxing Chancheng Hospital</name>
        <address>
          <city>Foshan</city>
          <state>Guangdong</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>The First Affiliated Hospital of Jinan University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Affiliated Hospital of Guizhou Medical University</name>
        <address>
          <city>Guiyang</city>
          <state>Guizhou</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Beijing Jishuitan Hospital Guizhou Hospital</name>
        <address>
          <city>Guiyang</city>
          <state>Guizhou</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Zunyi University Affiliated Hospital</name>
        <address>
          <city>Zunyi</city>
          <state>Guizhou</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Henan Provincial People's Hospital</name>
        <address>
          <city>Zhengzhou</city>
          <state>Henan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>People's Hospital of Wuhan University</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Wuhan Central Hospital</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Xiangya Third Hospital of Central South University</name>
        <address>
          <city>Changsha</city>
          <state>Hunan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>The First Affiliated Hospital of South China University</name>
        <address>
          <city>Hengyang</city>
          <state>Hunan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Lianyungang First People's Hospital</name>
        <address>
          <city>Lianyungang</city>
          <state>Jiangsu</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Nanjing First Hospital</name>
        <address>
          <city>Nanjing</city>
          <state>Jiangsu</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chengdu Second People's Hospital</name>
        <address>
          <city>Chengdu</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Chengdu Third People's Hospital</name>
        <address>
          <city>Chengdu</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Sichuan Provincial People's Hospital</name>
        <address>
          <city>Chengdu</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Guangyuan First People's Hospital</name>
        <address>
          <city>Guangyuan</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Mianyang Central Hospital</name>
        <address>
          <city>Mianyang</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Yibin Second People's Hospital</name>
        <address>
          <city>Yibin</city>
          <state>Sichuan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>The First People's Hospital of Yunnan Province</name>
        <address>
          <city>Kunming</city>
          <state>Yunnan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Sino-Japanese Friendship Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 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>Pain, Postoperative</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06007066
  org study id: HSK16149-204
  nct id: NCT06007066
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study will compare the effect and safety of HSK16149 with placebo on perioperative
        analgesia in orthopedic surgery, and explore the dosage of HSK16149 capsules for orthopedic
        analgesia during perioperative period.
  This study included patients who have orthopedic surgery under general anesthetic, with
        expected operation time ≤4h.
  
        Subjects were given 40mg or 60mg of HSK16149 or placebo orally the night before surgery, 2h
        before surgery, 4h and 16h after surgery, for a total of 4 times during the whole treatment
        period.
  
        Subjects will receive intravenous patient-controlled analgesia (PCA) morphine for pain in the
        immediate postoperative period. If PCA is insufficient, rescue analgesia of morphine may be
        given I.V. as determined by the investigator.
  
        After the treatment period, the subjects will be followed up.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Morphine Consumption
  time frame: Participants received PCA pump, an average of 24 hours after surgery
  description: IV Patient Controlled Analgesia (PCA) morphine for pain management in the immediate postoperative period for an average of 24 hours after surgery. If PCA is insufficient, rescue analgesia of morphine may be given I.V. as determined by the investigator.
  Total morphine consumption = PCA morphine consumption + rescue analgesia morphine consumption.
  measure: NRS at rest and during exercise
  time frame: 1, 2, 6, 12, 18, and 24 hours after surgery
  description: NRS:0 (no pain) to 10 (worst possible pain)
  measure: Time of first rescue analgesia with morphine after surgery
  time frame: Within 24 hours after surgery
  measure: Incidence of adverse reactions associated with morphine
  time frame: Within 24 hours after surgery
  measure: The frequency of rescue analgesia with morphine
  time frame: Within 24 hours after surgery
  measure: The total number of PCA presses and the number of effective PCA presses
  time frame: Within 24 hours after surgery
  measure: Daily Sleep Interference Scale (DSIS)
  time frame: Within 24 hours after surgery
  description: Subjects review their sleep status during the past 12 hours at 8:00 a.m. on the day of surgery.
  DSIS: 0 (not affecting sleep) to 10 (unable to sleep)
  measure: Subjects analgesic satisfaction score
  time frame: Within 24 hours after surgery
  description: Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied)
  measure: Investigators analgesic satisfaction score
  time frame: Within 24 hours after surgery
  description: Analgesic satisfaction score: 0 (not satisfied) to 10 (very satisfied)
  measure: Number of participants with treatment-related adverse events(TEAE) as assessed by CTCAE v5.0.
  time frame: From enrollment to 72 hours after surgery
  description: Number and severity of AEs, clinical laboratory abnormalities, physical examinations, 12-lead electrocardiograms (ECGs)(including QT Interval,QTc Interval and PR Interval), and vital signs.
  arm group label: Preoperative administration of HSK16149 40mg
  arm group type: Experimental
  description: HSK16149 40mg will be administered the night before and 2h before surgery
  arm group label: Preoperative administration of HSK16149 60mg
  arm group type: Experimental
  description: HSK16149 60mg will be administered the night before and 2h before surgery
  arm group label: Preoperative and postoperative administration of HSK16149 40mg
  arm group type: Experimental
  description: HSK16149 40mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery
  arm group label: Preoperative and postoperative administration of HSK16149 60mg
  arm group type: Experimental
  description: HSK16149 60mg will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery
  arm group label: placebo
  arm group type: Placebo Comparator
  description: The placebo will be administered orally the night before surgery, 2h before surgery, 4h and 16h after surgery
  intervention type: Drug
  intervention name: HSK16149 capsule
  description: Subjects will be given 40mg or 60mg of HSK16149 orally.
  arm group label: Preoperative administration of HSK16149 40mg
  arm group label: Preoperative administration of HSK16149 60mg
  arm group label: Preoperative and postoperative administration of HSK16149 40mg
  arm group label: Preoperative and postoperative administration of HSK16149 60mg
  other name: HSK16149
  intervention type: Drug
  intervention name: Placebo
  description: Subjects will be given HSK16149 placebo orally.
  arm group label: placebo
  other name: HSK16149 placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  facility: 
  country: China
  responsible party type: Sponsor
  mesh term: Pain, Postoperative
  sharing ipd: No