<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/NCT03808844</url>
  </required_header>
  <id_info>
    <org_study_id>HSK3486-302</org_study_id>
    <nct_id>NCT03808844</nct_id>
  </id_info>
  <brief_title>A Trial Evaluating the Efficacy and Safety of HSK3486 Injectable Emulsion for the Induction of General Anesthesia in Elective Surgery Subjects</brief_title>
  <official_title>A Multi-Center, Randomized, Double-Blind, Propofol-Controlled Phase III Clinical Trial Evaluating the Efficacy and Safety of HSK3486 Injectable Emulsion for the Induction of General Anesthesia in Elective Surgery Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sichuan 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>Yes</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 is a multi-center, randomized, double-blind, propofol-controlled phase III clinical&#xD;
      trial. The primary objective is to compare the efficacy and safety between propofol and&#xD;
      HSK3486 for the induction of general anesthesia in elective surgery subjects, so as to&#xD;
      provide reference for marketing registration of HSK3486.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 22, 2019</start_date>
  <completion_date type="Actual">September 3, 2019</completion_date>
  <primary_completion_date type="Actual">August 14, 2019</primary_completion_date>
  <phase>Phase 3</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 success rate of induction of anesthesia</measure>
    <time_frame>During induction of general anesthesia on day 1</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to successful anesthetic induction</measure>
    <time_frame>From the initial administration of the investigational drug to the first time when MOAA/S is ≤1 on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to loss of eyelash reflex</measure>
    <time_frame>From the initial administration of the investigational drug to loss of eyelash reflex on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of the investigational drug and alternative drugs</measure>
    <time_frame>During induction of general anesthesia on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of the alternative drugs</measure>
    <time_frame>During induction of general anesthesia on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in bispectral index (BIS)（score：0~100）</measure>
    <time_frame>During induction of general anesthesia on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Pre-dose to 48 hours post-dose</time_frame>
    <description>Safety endpoints</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">178</enrollment>
  <condition>Induction of Anesthesia</condition>
  <arm_group>
    <arm_group_label>HSK3486</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.4mg/kg/0.2 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2.0mg/kg/1.0mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK3486</intervention_name>
    <description>Initial dose of 0.4 mg/kg followed by 0.2 mg/kg if needed.</description>
    <arm_group_label>HSK3486</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Initial dose of 2.0 mg/kg followed by 1.0 mg/kg if needed</description>
    <arm_group_label>Propofol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. In-patients requiring tracheal intubation under general anesthesia for non-emergency,&#xD;
             non-cardiothoracic, and non-extracerebral elective surgeries;&#xD;
&#xD;
          2. Male or female, ages between 18-64 (inclusive);&#xD;
&#xD;
          3. ASA (American Society of Anesthesiologists) Class I-II (see Appendix 4);&#xD;
&#xD;
          4. Body mass index (BMI) ≥18 and ≤30 kg/m2;&#xD;
&#xD;
          5. Vital signs: Respiratory rate ≥10 and ≤24 breaths per minute; blood oxygen saturation&#xD;
             (SpO2) when inhaling ≥95%; systolic blood pressure (SBP) ≥90 mmHg and ≤160 mmHg;&#xD;
             diastolic blood pressure (DBP) ≥60 mmHg and ≤100 mmHg; heart rate ≥55 and ≤100 bpm;&#xD;
&#xD;
          6. Subjects must understand the procedures and methods of this study, and be willing to&#xD;
             provide informed consent and to complete the trial in strict accordance with study&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with contraindications to general anesthesia or previous history of&#xD;
             anesthesia accidents;&#xD;
&#xD;
          2. Known hypersensitivity to excipients and ingredients found in propofol and HSK3486&#xD;
             injections (soybean oil, glycerin, triglycerides, egg lecithin, sodium oleate, and&#xD;
             sodium hydroxide), benzodiazepines, opioids, rocuronium bromide, sevoflurane,&#xD;
             atropine, and neostigmine; cross-reactivity to halogenated anesthetics, jaundice or&#xD;
             unexplained fever from previous use of halogenated anesthetics; contraindications to&#xD;
             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 or SBP &gt;160 mmHg&#xD;
                  and/or DBP &gt;100 mmHg despite antihypertensive treatment, severe arrhythmia, heart&#xD;
                  failure, Adams-Stokes syndrome, unstable angina, myocardial infarction within 6&#xD;
                  months before screening, history of tachycardia/bradycardia requiring medication,&#xD;
                  third-degree atrioventricular block or QTcF interval ≥450 ms (Fridericia's&#xD;
                  correction formula, see Appendix 2) during screening;&#xD;
&#xD;
               2. Respiratory system disorders: Respiratory insufficiency, history of obstructive&#xD;
                  pulmonary disease, history of bronchospasm requiring treatment within 3 months&#xD;
                  prior to screening, acute respiratory tract infection with obvious symptoms such&#xD;
                  as fever, wheezing, or productive cough within 1 week prior to baseline;&#xD;
&#xD;
               3. History of cerebrovascular disease: History of craniocerebral injury,&#xD;
                  convulsions, epilepsy, intracranial hypertension, cerebral aneurysm, or&#xD;
                  cerebrovascular accident; history of schizophrenia, mania, chronic use of&#xD;
                  antipsychotics, or cognitive impairment;&#xD;
&#xD;
               4. Gastrointestinal disease history: Gastrointestinal retention, active hemorrhage,&#xD;
                  or circumstances that may lead to reflux and aspiration;&#xD;
&#xD;
               5. Patient with a history of uncontrolled and clinically significant liver, kidney,&#xD;
                  blood system, nervous system or metabolic system diseases judged by the&#xD;
                  investigator to be unsuitable for this trial;&#xD;
&#xD;
               6. History of alcohol abuse within 3 months prior to screening, abuse defined as&#xD;
                  average of &gt;2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor with&#xD;
                  40% alcohol or 150 mL wine);&#xD;
&#xD;
               7. History of drug abuse within 3 months prior to screening;&#xD;
&#xD;
               8. Serious infection, trauma, or major surgery within 4 weeks prior to screening;&#xD;
&#xD;
          4. Any one of the following respiratory risks before/during screening:&#xD;
&#xD;
               1. Asthma history, and stridor;&#xD;
&#xD;
               2. Sleep apnea syndrome;&#xD;
&#xD;
               3. History of malignant hyperthermia or family history;&#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 score III or IV );&#xD;
&#xD;
          5. In receipt of any of the following drugs or therapies prior to screening:&#xD;
&#xD;
               1. Participated in other drug trials within 1 month prior to screening;&#xD;
&#xD;
               2. In receipt of medications that may affect QT interval within 2 weeks prior to&#xD;
                  screening (see Appendix 5);&#xD;
&#xD;
               3. In receipt of medications that induce or inhibit cytochrome P450 isoenzyme CYP2B6&#xD;
                  within 2 weeks prior to screening (see Appendix 6);&#xD;
&#xD;
               4. In receipt of propofol, other sedatives/anesthetics, and/or opioid analgesics or&#xD;
                  compounds containing analgesics within 3 days prior to screening.&#xD;
&#xD;
          6. Laboratory results meeting any of the following criteria during screening/at baseline,&#xD;
             confirmed by re-examination:&#xD;
&#xD;
               1. Neutrophil count ≤1.5×109/L;&#xD;
&#xD;
               2. Platelet count &lt;80×109/L;&#xD;
&#xD;
               3. Hemoglobin &lt;90 g/L (no blood transfusion within the last 14 days);&#xD;
&#xD;
               4. ALT and/or AST ≥2.0×upper limit of normal (ULN);&#xD;
&#xD;
               5. Total bilirubin ≥2.0×ULN;&#xD;
&#xD;
               6. Serum creatinine ≥1.5×ULN.&#xD;
&#xD;
          7. Women who are pregnant or breastfeeding; women of child-bearing potential or men who&#xD;
             are unwilling to use contraception during the trial; subjects who are planning&#xD;
             pregnancy within 1 month after the completion of the trial (including male subjects);&#xD;
&#xD;
          8. Subjects judged by the investigator to be unsuitable for participating in this trial&#xD;
             for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 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>December 2018</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>September 11, 2019</last_update_submitted>
  <last_update_submitted_qc>September 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propofol</mesh_term>
  </intervention_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/NCT03808844
org study id: HSK3486-302
nct id: NCT03808844
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, randomized, double-blind, propofol-controlled phase III clinical
      trial. The primary objective is to compare the efficacy and safety between propofol and
      HSK3486 for the induction of general anesthesia in elective surgery subjects, so as to
      provide reference for marketing registration of HSK3486.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: The success rate of induction of anesthesia
time frame: During induction of general anesthesia on day 1
measure: Time to successful anesthetic induction
time frame: From the initial administration of the investigational drug to the first time when MOAA/S is ≤1 on day 1
measure: Time to loss of eyelash reflex
time frame: From the initial administration of the investigational drug to loss of eyelash reflex on day 1
measure: Use of the investigational drug and alternative drugs
time frame: During induction of general anesthesia on day 1
measure: Use of the alternative drugs
time frame: During induction of general anesthesia on day 1
measure: Changes in bispectral index (BIS)（score：0~100）
time frame: During induction of general anesthesia on day 1
measure: Number of patients with adverse events
time frame: Pre-dose to 48 hours post-dose
description: Safety endpoints
arm group label: HSK3486
arm group type: Experimental
description: 0.4mg/kg/0.2 mg/kg
arm group label: Propofol
arm group type: Active Comparator
description: 2.0mg/kg/1.0mg/kg
intervention type: Drug
intervention name: HSK3486
description: Initial dose of 0.4 mg/kg followed by 0.2 mg/kg if needed.
arm group label: HSK3486
intervention type: Drug
intervention name: Propofol
description: Initial dose of 2.0 mg/kg followed by 1.0 mg/kg if needed
arm group label: Propofol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Propofol