<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/NCT04470128</url>
  </required_header>
  <id_info>
    <org_study_id>HSK21542-202</org_study_id>
    <nct_id>NCT04470128</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Efficacy and Safety of HSK21542 Injection for Analgesia in Subjects Undergoing Colonoscopy</brief_title>
  <official_title>A Multi-center, Randomized, Two-stage, Phase II Clinical Study Evaluating the Efficacy and Safety of HSK21542 Injection for Analgesia in Subjects Undergoing Diagnostic or Therapeutic Colonoscopy</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 multi-center, randomized, two-stage, phase II clinical study .The main objective is&#xD;
      to evaluate the safety and tolerability of HSK21542 injection for analgesia in patients&#xD;
      undergoing colonoscopy, and, combining the pharmacodynamic (PD) and pharmacokinetic (PK)&#xD;
      characteristics&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Actual">January 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 28, 2020</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>None (Open Label)</masking>
    <masking_description>Stage I is open-label,Stage II is double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>BPS-NI score&gt;3 did not reach the proportion</measure>
    <time_frame>From administration until 24 hours after administration</time_frame>
    <description>the proportion of subjects with BPS-NI score&gt;3 did not appear from the beginning of insertion of colonoscopy to the removal of colonoscopy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of occurrences of BPS-NI score of &gt; 3</measure>
    <time_frame>From administration until 24 hours after administration</time_frame>
    <description>The ratio of subjects with BPS-NI scores of &gt; 3 for 0, 1, 2, 3, or more times from the insertion to the removal of colonoscope</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NRS score</measure>
    <time_frame>From administration until 24 hours after administration</time_frame>
    <description>NRS score of resting pain at each time point after the subject is fully awake</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose of propofol used</measure>
    <time_frame>From the first dose of the study drug to removal of colonoscope on day 1</time_frame>
    <description>The total dose used during the induction period, maintenance period, and the entire study process</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Success rate of colonoscopy diagnosis and treatment</measure>
    <time_frame>From the first dose of the study drug to removal of colonoscope on day 1</time_frame>
    <description>The following two conditions must be met for successful diagnosis and treatment:&#xD;
complete colonoscopy diagnosis and treatment and failure to use remedial analgesics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to full recovery</measure>
    <time_frame>On day 1</time_frame>
    <description>The time from the removal of colonoscope to when the subject opens his/her eyes and can tell his/her date of birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to discharge</measure>
    <time_frame>On day 1</time_frame>
    <description>The time from the removal of colonoscope to the occurrence of 3 consecutive Aldrete score of ≥ 9</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of AEs</measure>
    <time_frame>from signing the informed consent form to the follow-up period</time_frame>
    <description>Adverse event/serious adverse event</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Analgesia</condition>
  <arm_group>
    <arm_group_label>Stage I: HSK21542 0.5 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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>intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II : HSK21542 0.5 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II : HSK21542 1 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II : HSK21542 2 μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II : placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>intravenous injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I: HSK21542 0.5 μg/kg</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage I: HSK21542 0.5 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stage I: HSK21542 1 μg/kg</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage I: HSK21542 1 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK21542 0.5 μg/kg</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage II : HSK21542 0.5 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK21542 1 μg/kg</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage II : HSK21542 1 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK21542 2 μg/kg</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage II : HSK21542 2 μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Stage II : placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects undergoing diagnostic and/or therapeutic colonoscopy with an estimated&#xD;
             operation duration of 15-45 min;&#xD;
&#xD;
          2. Aged ≥ 18 and ≤ 75 years old, with no restriction on gender;&#xD;
&#xD;
          3. American Society of Anesthesiologists (ASA) Class I-II;&#xD;
&#xD;
          4. BMI ≥ 18 kg/m^2 and ≤ 30 kg/m^2;&#xD;
&#xD;
          5. During screening and at baseline: respiratory rate ≥ 10 and ≤ 24 bpm; SpO2 ≥ 95%&#xD;
             during inhalation; SBP ≥ 90 mmHg; DBP ≥ 50 mmHg; HR ≥ 50 and ≤ 100 bpm;&#xD;
&#xD;
          6. Subjects with intelligence and consciousness sufficient enough for cooperating with&#xD;
             the study;&#xD;
&#xD;
          7. Capable of understanding the procedure and method of this study, willing to sign an&#xD;
             informed consent form and to complete this study in strict accordance with the study&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients having contraindications to deep sedation/general anesthesia or a history of&#xD;
             past sedation/anesthesia accidents;&#xD;
&#xD;
          2. Patients with past history of allergy or contraindications to opioids, their rescue&#xD;
             medications, and propofol;&#xD;
&#xD;
          3. Medical history or evidence of any of the following prior to screening/at baseline,&#xD;
             which may increase sedation/anesthesia risk:&#xD;
&#xD;
               1. History of cardiovascular diseases: uncontrolled hypertension (systolic blood&#xD;
                  pressure [SBP] ≥ 170 mmHg and/or diastolic blood pressure [DBP] ≥ 105 mmHg&#xD;
                  without treatment, or SBP &gt; 160 mmHg and/or DBP &gt; 100 mmHg after antihypertensive&#xD;
                  treatment), severe arrhythmia, heart failure, Adams-Stokes syndrome, New York&#xD;
                  Heart Association (NYHA) Class ≥ III, severe superior vena cava syndrome,&#xD;
                  pericardial effusion, acute myocardial ischemia, unstable angina, myocardial&#xD;
                  infarction within 6 months before screening, history of tachycardia/bradycardia&#xD;
                  requiring medical treatment, II-III degree atrioventricular block (excluding&#xD;
                  patients with pacemakers);&#xD;
&#xD;
               2. History of respiratory system disorders: respiratory insufficiency, history of&#xD;
                  obstructive pulmonary disease, history of bronchospasm requiring treatment within&#xD;
                  3 months prior to screening, acute respiratory tract infection with obvious&#xD;
                  symptoms such as fever, wheezing, nasal obstruction, and cough within 1 week&#xD;
                  prior to baseline;&#xD;
&#xD;
               3. History of neurological and psychiatric disorders: craniocerebral injury,&#xD;
                  possible convulsions, myoclonus, intracranial hypertension, cerebral aneurysms,&#xD;
                  history of cerebrovascular accidents; schizophrenia, mania, insanity, long-term&#xD;
                  use of psychotropic drugs, and history of cognitive dysfunction; history of&#xD;
                  depression, anxiety, and epilepsy, etc.;&#xD;
&#xD;
               4. History of gastrointestinal disorders: gastrointestinal retention, active&#xD;
                  hemorrhage, or conditions that may lead to reflux and aspiration;&#xD;
&#xD;
               5. History of alcohol abuse within 3 months prior to screening, with abuse defined&#xD;
                  as average of &gt; 2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor&#xD;
                  with 40% alcohol or 150 mL wine);&#xD;
&#xD;
               6. History of drug abuse within 3 months prior to screening;&#xD;
&#xD;
               7. History of blood donation or blood loss of ≥ 400 mL within 3 months prior to&#xD;
                  screening;&#xD;
&#xD;
          4. Patients with the following airway management risks:&#xD;
&#xD;
               1. Asthma history, and stridor;&#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. Judged by the investigator to have difficult airway or judged as difficult&#xD;
                  tracheal intubation (modified Mallampati class IV) at screening;&#xD;
&#xD;
          5. In receipt of any one of the following medications or treatments at screening:&#xD;
&#xD;
               1. A time between the last use of opioid and non-opioid (such as paracetamol,&#xD;
                  aspirin [daily dose &gt; 100 mg], indomethacin, diclofenac, parecoxib sodium, and&#xD;
                  other non-steroidal anti-inflammatory drugs) analgesics and randomization of&#xD;
                  shorter than 5 half-lives of the drug or the duration of the drug's efficacy&#xD;
                  (whichever is longer);&#xD;
&#xD;
               2. Longer than 10 days of continuous use of opioid analgesics for any reason within&#xD;
                  3 months prior to 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, and midazolam] and non-benzodiazepines [zolpidem,&#xD;
                  zopiclone, zaleplon]), sedative-anesthetics (sevoflurane, nitrous oxide,&#xD;
                  ketamine, and etomidate), glucocorticoids (dexamethasone hydrochloride and&#xD;
                  methylprednisolone), antiepileptics (carbamazepine and sodium valproate),&#xD;
                  anxiolytics (chlordiazepoxide), antidepressants (imipramine and amitriptyline),&#xD;
                  and Chinese herbal medicines or Chinese patent medicines with analgesic and&#xD;
                  sedative effects;&#xD;
&#xD;
               4. A time between randomization and the last use of diuretics and compound drugs&#xD;
                  containing diuretics of shorter than 5 half-lives of the drug or the duration of&#xD;
                  the drug's efficacy (whichever is longer);&#xD;
&#xD;
          6. Patient whose laboratory parameters measured at screening reach the following criteria&#xD;
             and are verified through reexamination:&#xD;
&#xD;
               1. WBC &lt; 3.0 × 10^9/L;&#xD;
&#xD;
               2. Platelet count &lt; 80 × 10^9/L;&#xD;
&#xD;
               3. Hemoglobin &lt; 80 g/L;&#xD;
&#xD;
               4. Prothrombin time &gt; 1.5 × ULN;&#xD;
&#xD;
               5. Activated partial thromboplastin time &gt; 1.5 × ULN;&#xD;
&#xD;
               6. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 × ULN;&#xD;
&#xD;
               7. Total bilirubin &gt; 1.5 × ULN;&#xD;
&#xD;
               8. Blood creatinine &gt; 1.5 × ULN;&#xD;
&#xD;
          7. Having participated in other drug clinical trials within 3 months prior to screening&#xD;
             (defined as having received investigational product or placebo);&#xD;
&#xD;
          8. Pregnant or breastfeeding females: women or men of child-bearing potential who are&#xD;
             unwilling to use contraception during the trial; subjects who are planning pregnancy&#xD;
             within 3 months after the trial (including male subjects);&#xD;
&#xD;
          9. Subject judged by the investigator to have any other factors unsuitable for&#xD;
             involvement in the study.&#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>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 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/NCT04470128
org study id: HSK21542-202
nct id: NCT04470128
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, randomized, two-stage, phase II clinical study .The main objective is
      to evaluate the safety and tolerability of HSK21542 injection for analgesia in patients
      undergoing colonoscopy, and, combining the pharmacodynamic (PD) and pharmacokinetic (PK)
      characteristics
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Stage I is open-label,Stage II is double-blind
measure: BPS-NI score>3 did not reach the proportion
time frame: From administration until 24 hours after administration
description: the proportion of subjects with BPS-NI score>3 did not appear from the beginning of insertion of colonoscopy to the removal of colonoscopy
measure: Number of occurrences of BPS-NI score of > 3
time frame: From administration until 24 hours after administration
description: The ratio of subjects with BPS-NI scores of > 3 for 0, 1, 2, 3, or more times from the insertion to the removal of colonoscope
measure: NRS score
time frame: From administration until 24 hours after administration
description: NRS score of resting pain at each time point after the subject is fully awake
measure: Dose of propofol used
time frame: From the first dose of the study drug to removal of colonoscope on day 1
description: The total dose used during the induction period, maintenance period, and the entire study process
measure: Success rate of colonoscopy diagnosis and treatment
time frame: From the first dose of the study drug to removal of colonoscope on day 1
description: The following two conditions must be met for successful diagnosis and treatment:
complete colonoscopy diagnosis and treatment and failure to use remedial analgesics
measure: Time to full recovery
time frame: On day 1
description: The time from the removal of colonoscope to when the subject opens his/her eyes and can tell his/her date of birth
measure: Time to discharge
time frame: On day 1
description: The time from the removal of colonoscope to the occurrence of 3 consecutive Aldrete score of ≥ 9
measure: The incidence and severity of AEs
time frame: from signing the informed consent form to the follow-up period
description: Adverse event/serious adverse event
arm group label: Stage I: HSK21542 0.5 μg/kg
arm group type: Experimental
description: intravenous injection
arm group label: Stage I: HSK21542 1 μg/kg
arm group type: Experimental
description: intravenous injection
arm group label: Stage II : HSK21542 0.5 μg/kg
arm group type: Experimental
description: intravenous injection
arm group label: Stage II : HSK21542 1 μg/kg
arm group type: Experimental
description: intravenous injection
arm group label: Stage II : HSK21542 2 μg/kg
arm group type: Experimental
description: intravenous injection
arm group label: Stage II : placebo
arm group type: Placebo Comparator
description: intravenous injection
intervention type: Drug
intervention name: Stage I: HSK21542 0.5 μg/kg
description: intravenous injection
arm group label: Stage I: HSK21542 0.5 μg/kg
intervention type: Drug
intervention name: Stage I: HSK21542 1 μg/kg
description: intravenous injection
arm group label: Stage I: HSK21542 1 μg/kg
intervention type: Drug
intervention name: HSK21542 0.5 μg/kg
description: intravenous injection
arm group label: Stage II : HSK21542 0.5 μg/kg
intervention type: Drug
intervention name: HSK21542 1 μg/kg
description: intravenous injection
arm group label: Stage II : HSK21542 1 μg/kg
intervention type: Drug
intervention name: HSK21542 2 μg/kg
description: intravenous injection
arm group label: Stage II : HSK21542 2 μg/kg
intervention type: Drug
intervention name: Placebo
description: intravenous injection
arm group label: Stage II : placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Agnosia