<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/NCT04422496</url>
  </required_header>
  <id_info>
    <org_study_id>HEC96719-P-03</org_study_id>
    <nct_id>NCT04422496</nct_id>
  </id_info>
  <brief_title>The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of HEC96719 Tablets in Healthy Subjects</brief_title>
  <official_title>A Phase I, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Clinical Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HEC96719 Tablets in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunshine Lake Pharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunshine Lake Pharma 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>
      The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Non-alcoholic fatty&#xD;
      liver disease (NAFLD) treatment drug HEC96719 in Healthy Male and Female Subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study consists of a single-dose study and a multiple-dose study, both using a&#xD;
      single-center, randomized, double-blind, placebo-controlled, dose-escalation design： I.&#xD;
      Single-Dose Study There will be a total of 6 dose cohorts. Each cohort will include 10&#xD;
      subjects, of which 8 receives HEC96719 tablets and 2 receives placebo, regardless of gender.&#xD;
      Each subject will only participate in one dose cohort. Each cohort will be divided into 2&#xD;
      group. The first group consists of 2 sentinels, one receiving active and one placebo. The&#xD;
      second group will consist of the remainder of the cohort (7 active and 1 placebo) and,&#xD;
      following review of the available safety data, will be dosed 48 hours after the sentinel&#xD;
      group. Subjects can leave the pharmacy after their biological samples are collected on day 3.&#xD;
      The last safety follow-up visit is to be performed on day 7±1 via telephone. Subjects in each&#xD;
      cohort will receive a single dose of HEC96719 or placebo in the fasted state on day 1, and&#xD;
      safety evaluation is to be performed on day 3 and 7.&#xD;
&#xD;
      II. Multi-Dose Study There will be a total of 3 dose cohorts. Each cohort will consist of 12&#xD;
      subjects, of which 10 receive HEC96719 tablets and 2 receive placebo, the dose regimen will&#xD;
      comprise no less than once a day and will not exceed 4 times daily dosing for 7 consecutive&#xD;
      days (study doses, administration method (fasted or fed), dosing frequency, and dosing period&#xD;
      are all to be determined based on data from the single-dose study and multiple-dose study).&#xD;
      Each subject will only participate in one dose cohort. Subjects will reside at the pharmacy&#xD;
      from the day before dosing (D-1) to 96 h after the last dose. Subjects can leave pharmacy&#xD;
      after their biological samples are collected. The last safety follow-up visit is to be&#xD;
      performed 168±24 h after the last dose via telephone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Actual">February 23, 2021</completion_date>
  <primary_completion_date type="Actual">February 23, 2021</primary_completion_date>
  <phase>Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse event</measure>
    <time_frame>Baseline to day 21</time_frame>
    <description>To assess the safety and tolerability of therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>predose to 96 hour after dosing</time_frame>
    <description>maximum observed plasma concentration of HEC96719</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC</measure>
    <time_frame>predose to 96 hour after dosing</time_frame>
    <description>area under the plasma concentration-time curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T½</measure>
    <time_frame>predose to 96 hour after dosing</time_frame>
    <description>apparent terminal elimination half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>predose to 96 hour after dosing</time_frame>
    <description>time of the maximum observed plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C4</measure>
    <time_frame>predose to 48 hour after dosing</time_frame>
    <description>7α-hydroxy-4-cholestene-3-one</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FGF19</measure>
    <time_frame>predose to 48 hour after dosing</time_frame>
    <description>Fibroblast growth factor 19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F</measure>
    <time_frame>predose to 96 hour after dosing</time_frame>
    <description>apparent oral clearance</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Non-alcoholic Fatty Liver Disease</condition>
  <condition>Non-alcoholic Steatohepatitis</condition>
  <arm_group>
    <arm_group_label>HEC96719 tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>part A: There will be a total of 6 dose cohorts: 0.2 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg part B: There will be a total of 3 dose cohorts: 0.5 mg, 1 mg, 2 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo tablets</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>part A: There will be a total of 6 dose cohorts: 0.2 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg part B:There will be a total of 3 dose cohorts: 0.5 mg, 1 mg, 2 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HEC96719</intervention_name>
    <description>single-Dose Study: Each dose of HEC96719 and placebo will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.&#xD;
multiple-dose study:The study doses, administration method (fasted or fed), dosing frequency, and dosing period are all to be determined based on data from the single-dose study and multiple-dose study.</description>
    <arm_group_label>HEC96719 tablets</arm_group_label>
    <arm_group_label>placebo tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, of any race, between 18 and 55 years of age, inclusive, at&#xD;
             Screening.&#xD;
&#xD;
          2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.&#xD;
&#xD;
          3. In good health, determined by no clinically significant findings from medical history,&#xD;
             physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory&#xD;
             evaluations at Screening and/or Check-in as assessed by the Investigator (or&#xD;
             designee).&#xD;
&#xD;
          4. Females will be nonpregnant and nonlactating. Females of childbearing potential and&#xD;
             male subjects will agree to use contraception&#xD;
&#xD;
          5. Able to comprehend and willing to provide a written Informed Consent Form (ICF) and to&#xD;
             abide by the study restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Significant history or clinical manifestation of any metabolic, allergic,&#xD;
             dermatological, hepatic, renal, hematological, pulmonary, cardiovascular,&#xD;
             gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as&#xD;
             determined by the Investigator (or designee).&#xD;
&#xD;
          2. History of significant hypersensitivity, intolerance, or allergy to any drug compound,&#xD;
             food, or other substance, unless approved by the Investigator (or designee).&#xD;
&#xD;
          3. History of stomach or intestinal surgery or resection that would potentially alter&#xD;
             absorption and/or excretion of orally administered drugs (uncomplicated appendectomy&#xD;
             and hernia repair will be allowed).&#xD;
&#xD;
          4. History of gallstone disease or diseases affecting the bile ducts.&#xD;
&#xD;
          5. History of inflammation, ulceration, bleeding affecting the gastrointestinal tract.&#xD;
&#xD;
          6. Alanine transaminase (ALT) or Glutamic oxalacetic transaminase(AST) is out of the&#xD;
             normal range.&#xD;
&#xD;
          7. Bilirubin is more than 1.5 x upper limit of normal.&#xD;
&#xD;
          8. Positive test result for hepatitis B surface antigen, hepatitis C virus antibody,&#xD;
             and/or human immunodeficiency virus antibodies .&#xD;
&#xD;
          9. History of active tuberculosis or exposure to endemic areas within 8 weeks prior to&#xD;
             QuantiFERON®-tuberculosis(TB) testing performed at screening.&#xD;
&#xD;
         10. Positive QuantiFERON®-tuberculosis(TB) indicating possible tuberculosis infection.&#xD;
&#xD;
         11. Immunization with a live attenuated vaccine within 1 month prior to dosing or planned&#xD;
             vaccination during the course of the study.&#xD;
&#xD;
         12. History of clinically significant opportunistic infection e.g. invasive candidiasis or&#xD;
             pneumocystis pneumonia.&#xD;
&#xD;
         13. Serious local infection e.g. cellulitis, abscess, or systemic infection e.g.&#xD;
             septicemia, within 3 months prior to screening.&#xD;
&#xD;
         14. Presence of fever (body temperature &gt;37.6 °C) e.g. a fever associated with a&#xD;
             symptomatic viral or bacterial infection, within 2 weeks prior to the first dosing.&#xD;
&#xD;
         15. Subjects who are scheduled to receive an organ transplant or have received an organ&#xD;
             transplant;&#xD;
&#xD;
         16. Participation in a clinical study involving administration of an investigational drug&#xD;
             (new chemical entity) in the past 30 days or 5 half-lives (if known), whichever is&#xD;
             longer, prior to Check-in.&#xD;
&#xD;
         17. Use or intend to use any medications/products known to alter drug absorption,&#xD;
             metabolism, or elimination processes, including St. John's Wort, within 30 days prior&#xD;
             to Check-in, unless deemed acceptable by the Investigator (or designee).&#xD;
&#xD;
         18. Use or intend to use any prescription medications/products, within 14 days prior to&#xD;
             Check-in, unless deemed acceptable by the Investigator (or designee).&#xD;
&#xD;
         19. Use or intend to use any nonprescription medications/products including vitamins,&#xD;
             minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior&#xD;
             to Check-in, unless deemed acceptable by the Investigator (or designee).&#xD;
&#xD;
         20. History of drug abuse within 1 year prior to screening, or use of soft drugs (such as&#xD;
             marijuana) within 3 months prior to the screening, or hard drugs (such as cocaine,&#xD;
             phencyclidine, and crack) within 1 year prior to screening.&#xD;
&#xD;
         21. Alcohol consumption of &gt; 21 units per week for males and &gt; 14 units for females. One&#xD;
             unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL&#xD;
             wine), or a positive alcohol breath test at Check-in.&#xD;
&#xD;
         22. Positive urine drugs of abuse screen at Screening or Check-in.&#xD;
&#xD;
         23. Smokers of more than 5 cigarettes per week or positive cotinine test at Screening or&#xD;
             Check-in.&#xD;
&#xD;
         24. Consumption of foods and beverages containing poppy seeds, grapefruit, or Seville&#xD;
             oranges within 7 days prior to Check-in, consumption of caffeine-containing foods and&#xD;
             beverages within 72 hours prior to Check-in, or consumption of alcohol within 48 hours&#xD;
             prior to Check-in.&#xD;
&#xD;
         25. Receipt of blood products within 2 months prior to Check-in.&#xD;
&#xD;
         26. Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to&#xD;
             Screening, or platelets from 6 weeks prior to Screening.&#xD;
&#xD;
         27. Poor peripheral venous access.&#xD;
&#xD;
         28. Have previously completed or withdrawn from this study, and have previously received&#xD;
             the investigational product.&#xD;
&#xD;
         29. Subjects who, in the opinion of the Investigator (or designee), should not participate&#xD;
             in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jon Rankin, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Study Principal Investigator</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nucleus Network Pty Ltd</name>
      <address>
        <city>Melbourne</city>
        <state>Melbourne VIC 3004</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 6, 2021</last_update_submitted>
  <last_update_submitted_qc>May 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</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>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</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/NCT04422496
org study id: HEC96719-P-03
nct id: NCT04422496
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Non-alcoholic fatty
      liver disease (NAFLD) treatment drug HEC96719 in Healthy Male and Female Subjects
This study consists of a single-dose study and a multiple-dose study, both using a
      single-center, randomized, double-blind, placebo-controlled, dose-escalation design： I.
      Single-Dose Study There will be a total of 6 dose cohorts. Each cohort will include 10
      subjects, of which 8 receives HEC96719 tablets and 2 receives placebo, regardless of gender.
      Each subject will only participate in one dose cohort. Each cohort will be divided into 2
      group. The first group consists of 2 sentinels, one receiving active and one placebo. The
      second group will consist of the remainder of the cohort (7 active and 1 placebo) and,
      following review of the available safety data, will be dosed 48 hours after the sentinel
      group. Subjects can leave the pharmacy after their biological samples are collected on day 3.
      The last safety follow-up visit is to be performed on day 7±1 via telephone. Subjects in each
      cohort will receive a single dose of HEC96719 or placebo in the fasted state on day 1, and
      safety evaluation is to be performed on day 3 and 7.

      II. Multi-Dose Study There will be a total of 3 dose cohorts. Each cohort will consist of 12
      subjects, of which 10 receive HEC96719 tablets and 2 receive placebo, the dose regimen will
      comprise no less than once a day and will not exceed 4 times daily dosing for 7 consecutive
      days (study doses, administration method (fasted or fed), dosing frequency, and dosing period
      are all to be determined based on data from the single-dose study and multiple-dose study).
      Each subject will only participate in one dose cohort. Subjects will reside at the pharmacy
      from the day before dosing (D-1) to 96 h after the last dose. Subjects can leave pharmacy
      after their biological samples are collected. The last safety follow-up visit is to be
      performed 168±24 h after the last dose via telephone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adverse event
time frame: Baseline to day 21
description: To assess the safety and tolerability of therapy.
measure: Cmax
time frame: predose to 96 hour after dosing
description: maximum observed plasma concentration of HEC96719
measure: AUC
time frame: predose to 96 hour after dosing
description: area under the plasma concentration-time curve (AUC)
measure: T½
time frame: predose to 96 hour after dosing
description: apparent terminal elimination half-life
measure: Tmax
time frame: predose to 96 hour after dosing
description: time of the maximum observed plasma concentration
measure: C4
time frame: predose to 48 hour after dosing
description: 7α-hydroxy-4-cholestene-3-one
measure: FGF19
time frame: predose to 48 hour after dosing
description: Fibroblast growth factor 19
measure: CL/F
time frame: predose to 96 hour after dosing
description: apparent oral clearance
arm group label: HEC96719 tablets
arm group type: Experimental
description: part A: There will be a total of 6 dose cohorts: 0.2 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg part B: There will be a total of 3 dose cohorts: 0.5 mg, 1 mg, 2 mg
arm group label: placebo tablets
arm group type: Placebo Comparator
description: part A: There will be a total of 6 dose cohorts: 0.2 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg part B:There will be a total of 3 dose cohorts: 0.5 mg, 1 mg, 2 mg
intervention type: Drug
intervention name: HEC96719
description: single-Dose Study: Each dose of HEC96719 and placebo will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.
multiple-dose study:The study doses, administration method (fasted or fed), dosing frequency, and dosing period are all to be determined based on data from the single-dose study and multiple-dose study.
arm group label: HEC96719 tablets
arm group label: placebo tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jon Rankin, Doctor
role: Principal Investigator
affiliation: Study Principal Investigator
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease