<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/NCT03751956</url>
  </required_header>
  <id_info>
    <org_study_id>HSK3486-104-2</org_study_id>
    <nct_id>NCT03751956</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Mass Balance of [14C]HSK3486 Emulsion Injection in Healthy Adults.</brief_title>
  <official_title>A Study Evaluating the Mass Balance and Biotransformation of [14C]HSK3486 Emulsion Injection in Healthy Chinese Male Adults.</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>
    <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 is designed to evaluate the mass balance and biotransformation pathways of HSK3486&#xD;
      in healthy Chinese male subjects administered with a single intravenous dose of [14C]HSK3486,&#xD;
      so as to characterize the drug's general pharmacokinetics and safety in humans and provide&#xD;
      supportive data for reasonable use.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 6, 2019</start_date>
  <completion_date type="Actual">March 10, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of cumulative drug excretion of [14C]HSK3486 on biological specimens(urine and faeces) accounting for total radiation drug dose</measure>
    <time_frame>From the start of administration through 168 hours after administration</time_frame>
    <description>Though collecting different periods of biological specimens(urine and faeces) , detecting their respective drug excretion of [14C]HSK3486，calculating the total cumulative excretion amount and relevant proportion of each kind of specimen(urine or faeces)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of total radioactivity and non-radiolabeled HSK3486 respectively</measure>
    <time_frame>From the start of administration through 168 hours after administration</time_frame>
    <description>Pharmacokinetic Measures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to plasma peak concentration[Tmax] of total radioactivity and non-radiolabeled HSK3486 respectively</measure>
    <time_frame>From the start of administration through 168 hours after administration</time_frame>
    <description>Pharmacokinetic Measures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance half-life[t1/2] of total radioactivity and non-radiolabeled HSK3486 respectively</measure>
    <time_frame>From the start of administration through 168 hours after administration</time_frame>
    <description>Pharmacokinetic Measures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve [AUC] of total radioactivity and non-radiolabeled HSK3486 respectively</measure>
    <time_frame>From the start of administration through 168 hours after administration</time_frame>
    <description>Pharmacokinetic Measures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The metabolite analysis of [14C]HSK3486 in human body</measure>
    <time_frame>from the start of administration through 168 hours after administration</time_frame>
    <description>Pharmacokinetic Measures</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events and serious adverse events</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Safety Measures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood routine test</measure>
    <time_frame>At the time of subject is being screened and at the end of study( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of blood routine test during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine routine test</measure>
    <time_frame>At the time of subject is being screened and at the end of study( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of urine routine test during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood biochemical examination</measure>
    <time_frame>At the time of subject is being screened and at the end of study( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of Blood biochemical examination during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of blood pressure during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate or pulse</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of heart rate or pulse during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory rate or blood oxygen saturation</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of respiratory rate or blood oxygen saturation during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of heart rate of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RR interval of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of RR interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QT interval of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of QT interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QTcF interval of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of QTcF interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PR interval of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of PR interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QRS interval of electrocardiogram</measure>
    <time_frame>From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)</time_frame>
    <description>Observe the changes of QRS interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Anesthesia</condition>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>HSK3486</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.8 μCi/0.4 mg/kg of [14C]HSK3486 emulsion injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK3486</intervention_name>
    <description>The subjects will receive an intravenous injection of 0.8 μCi/0.4 mg/kg of [14C]HSK3486 emulsion injection (i.e., a subject with the body weight of 60 kg is administered with a radiation dose of 48 μCi).</description>
    <arm_group_label>HSK3486</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects enrolled in this study are required to meet all of the following:&#xD;
&#xD;
               1. Healthy Chinese males aged 18-49 years old (inclusive);&#xD;
&#xD;
               2. Body weight: body mass index (BMI) between 19-26 kg/m2 (inclusive); weight should&#xD;
                  be no less than 50 kg; weight difference between the lightest and the heaviest&#xD;
                  subjects enrolled should be no more than 10 kg;&#xD;
&#xD;
               3. Vital signs: blood pressure between 90-140/60-90 mmHg; heart rate or pulse&#xD;
                  between 60-99 beats/min; body temperature (ear temperature) between 35.5-37.1 °C;&#xD;
                  respiratory rate between 12-24 breaths/min; blood oxygen saturation when inhaling&#xD;
                  ≥ 96% (inclusive);&#xD;
&#xD;
               4. Normal major organ function, e.g. routine blood test, blood biochemistry, routine&#xD;
                  urinalysis, feces and fecal occult blood test, and blood coagulation are all&#xD;
                  normal, or abnormal with no clinical significance as judged by the investigators;&#xD;
&#xD;
               5. Subjects who voluntarily sign the informed consent form, able to communicate well&#xD;
                  with the investigator and complete all trial procedures in accordance with the&#xD;
                  protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who meet any of the following will be excluded:&#xD;
&#xD;
               1. Subjects with clinically significant abnormalities during screening in physical&#xD;
                  examinations, laboratory tests, 12-lead ECG, chest X-ray or airway evaluation,&#xD;
                  including airway evaluation of a modified Mallampati score of IV; subjects with&#xD;
                  positive test result for hepatitis B surface antigen, hepatitis B e antigen,&#xD;
                  hepatitis C antibody, HIV antibody or syphilis antibody;&#xD;
&#xD;
               2. Medication history: In receipt of any other investigational drug or participated&#xD;
                  in any drug or medical device clinical trial within 3 months before screening; or&#xD;
                  in receipt of propofol, other sedative/narcotic drugs and/or opioid analgesics or&#xD;
                  compounds containing analgesics within 72 hours prior to screening; or in receipt&#xD;
                  of any prescription drugs, Chinese herbal medicines, over-the-counter drugs or&#xD;
                  food supplements (such as vitamins and calcium supplements) other than&#xD;
                  contraceptives, paracetamol, oral non-steroidal anti-inflammatory drugs, and&#xD;
                  topical over-the-counter preparations within 2 weeks before screening; subjects&#xD;
                  can only be enrolled given the condition that the primary investigator (PI) and&#xD;
                  the sponsor agree that the drug used has no effect on the safety and mass balance&#xD;
                  results of the trial;&#xD;
&#xD;
               3. Past and current medical history:&#xD;
&#xD;
                  A Subjects with a history of any severe disease, or concomitant diseases or&#xD;
                  abnormalities that may affect the test results as judged by the investigator,&#xD;
                  including but not limited to diseases or abnormalities in the circulatory system,&#xD;
                  endocrine system, neurological system, digestive system, urinary system,&#xD;
                  hematologic system, immune system, mental and metabolic aspects; B Subjects who&#xD;
                  have a past or current history of cardiovascular disease, including: heart&#xD;
                  failure, ischemic heart disease, long QT syndrome, arrhythmia requiring&#xD;
                  medication; a family history of Adams-Stokes syndrome or long QT syndrome; QTcF&#xD;
                  interval ≥ 450 ms (corrected by Fridericia's formula); C Subjects who have a past&#xD;
                  or current history of respiratory disease, including: obstructive pulmonary&#xD;
                  disease, asthma, or a history of bronchospasm requiring treatment within 3 months&#xD;
                  prior to screening; acute respiratory infections within 1 week prior to&#xD;
                  screening, with significant fever, wheezing, nasal congestion, and coughing.&#xD;
&#xD;
                  D Subjects who have a past or current history of gastrointestinal disease,&#xD;
                  including: gastroesophageal reflux, hemorrhoids or perianal disease with fecal&#xD;
                  blood, habitual constipation or diarrhea, irritable bowel syndrome, inflammatory&#xD;
                  bowel disease, etc.; E Subjects who have major surgery within 6 months before&#xD;
                  screening, or surgical incision not completely healed. Major surgery includes,&#xD;
                  but is not limited to any surgery that has a significant risk of bleeding,&#xD;
                  prolonged general anesthesia, incisional biopsy or significant traumatic injury;&#xD;
                  F Subjects with hyperactive immune response, including: sensitive to excipients&#xD;
                  of HSK3486 emulsion injections (soybean oil, glycerin, triglyceride, egg&#xD;
                  lecithin, sodium oleate and sodium hydroxide), history of drug allergies&#xD;
                  (including anesthetics), or other allergic diseases (such as allergic to any food&#xD;
                  ingredient or have special dietary requirements and cannot follow a uniform&#xD;
                  diet);&#xD;
&#xD;
               4. Alcohol abuse or history of alcohol abuse within 3 months prior to screening,&#xD;
                  e.g. &gt; 14 units of alcohol consumption per week (1 unit = 360 mL beer or 45 mL&#xD;
                  liquor with 40% alcohol or 150 mL wine), or positive result for breath alcohol&#xD;
                  test at screening;&#xD;
&#xD;
               5. Consumption of more than 5 cigarettes daily within 3 months before screening or&#xD;
                  habitual use of nicotine-containing products which cannot be withdrawn during the&#xD;
                  trial; history of respiratory irritation symptoms caused by smoking;&#xD;
&#xD;
               6. Chronic drug abuse or use of soft drugs (such as marijuana) within 3 months&#xD;
                  before screening; or use of hard drugs (such as cocaine, amphetamines,&#xD;
                  phencyclidine) within 1 year before screening; or any signs of chronic&#xD;
                  benzodiazepines use (such as insomnia, anxiety) or positive urine drug test&#xD;
                  during screening;&#xD;
&#xD;
               7. Habitual consumption of grapefruit juice or excessive tea, coffee and/or&#xD;
                  caffeinated beverages which cannot be withdrawn during the trial;&#xD;
&#xD;
               8. Engaged in work requiring long-term exposure to radioactive conditions; or&#xD;
                  significant radioactive exposure within 1 year prior to the trial (≥ 2 chest/&#xD;
                  abdominal CT, or ≥ 3 other types of X-ray tests); or those who have participated&#xD;
                  in radiolabelling testing;&#xD;
&#xD;
               9. Fertility planner during the trial period and within 1 year after the completion&#xD;
                  of the trial, or subjects or their spouses who refuse to take strict&#xD;
                  contraceptive measures (including taking condom, contraceptive sponge,&#xD;
                  contraceptive gel, diaphragm, intrauterine devices, oral or injectable&#xD;
                  contraceptives, subcutaneous implants, etc.) during the trial and within 1 year&#xD;
                  after the completion of the trial;&#xD;
&#xD;
              10. Subjects who received blood transfusion within 1 month before screening or who&#xD;
                  had blood loss or blood donation ≥ 200 mL, or subjects who had plasma donation or&#xD;
                  plasma exchange within 7 days before the trial;&#xD;
&#xD;
              11. Subject deemed unsuitable by the investigator for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>the First Affilicated Hospital of Soochow University</name>
      <address>
        <city>Suzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>November 18, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>October 25, 2019</last_update_submitted>
  <last_update_submitted_qc>October 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03751956
org study id: HSK3486-104-2
nct id: NCT03751956
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is designed to evaluate the mass balance and biotransformation pathways of HSK3486
      in healthy Chinese male subjects administered with a single intravenous dose of [14C]HSK3486,
      so as to characterize the drug's general pharmacokinetics and safety in humans and provide
      supportive data for reasonable use.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of cumulative drug excretion of [14C]HSK3486 on biological specimens(urine and faeces) accounting for total radiation drug dose
time frame: From the start of administration through 168 hours after administration
description: Though collecting different periods of biological specimens(urine and faeces) , detecting their respective drug excretion of [14C]HSK3486，calculating the total cumulative excretion amount and relevant proportion of each kind of specimen(urine or faeces)
measure: Maximum Plasma Concentration [Cmax] of total radioactivity and non-radiolabeled HSK3486 respectively
time frame: From the start of administration through 168 hours after administration
description: Pharmacokinetic Measures
measure: Time to plasma peak concentration[Tmax] of total radioactivity and non-radiolabeled HSK3486 respectively
time frame: From the start of administration through 168 hours after administration
description: Pharmacokinetic Measures
measure: Clearance half-life[t1/2] of total radioactivity and non-radiolabeled HSK3486 respectively
time frame: From the start of administration through 168 hours after administration
description: Pharmacokinetic Measures
measure: Area Under the Curve [AUC] of total radioactivity and non-radiolabeled HSK3486 respectively
time frame: From the start of administration through 168 hours after administration
description: Pharmacokinetic Measures
measure: The metabolite analysis of [14C]HSK3486 in human body
time frame: from the start of administration through 168 hours after administration
description: Pharmacokinetic Measures
measure: Number of patients with adverse events and serious adverse events
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Safety Measures
measure: Blood routine test
time frame: At the time of subject is being screened and at the end of study( nearly 168h after drug administration)
description: Observe the changes of blood routine test during the whole trial
measure: Urine routine test
time frame: At the time of subject is being screened and at the end of study( nearly 168h after drug administration)
description: Observe the changes of urine routine test during the whole trial
measure: Blood biochemical examination
time frame: At the time of subject is being screened and at the end of study( nearly 168h after drug administration)
description: Observe the changes of Blood biochemical examination during the whole trial
measure: Blood pressure
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of blood pressure during the whole trial
measure: Heart rate or pulse
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of heart rate or pulse during the whole trial
measure: Respiratory rate or blood oxygen saturation
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of respiratory rate or blood oxygen saturation during the whole trial
measure: Heart rate of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of heart rate of electrocardiogram during the whole trial
measure: RR interval of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of RR interval of electrocardiogram during the whole trial
measure: QT interval of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of QT interval of electrocardiogram during the whole trial
measure: QTcF interval of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of QTcF interval of electrocardiogram during the whole trial
measure: PR interval of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of PR interval of electrocardiogram during the whole trial
measure: QRS interval of electrocardiogram
time frame: From the time the subject is being screened to the end of the trial( nearly 168h after drug administration)
description: Observe the changes of QRS interval of electrocardiogram during the whole trial
arm group label: HSK3486
arm group type: Experimental
description: 0.8 μCi/0.4 mg/kg of [14C]HSK3486 emulsion injection
intervention type: Drug
intervention name: HSK3486
description: The subjects will receive an intravenous injection of 0.8 μCi/0.4 mg/kg of [14C]HSK3486 emulsion injection (i.e., a subject with the body weight of 60 kg is administered with a radiation dose of 48 μCi).
arm group label: HSK3486
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor