<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/NCT04480697</url>
  </required_header>
  <id_info>
    <org_study_id>HPG1860-101</org_study_id>
    <nct_id>NCT04480697</nct_id>
  </id_info>
  <brief_title>Study of Safety, Tolerability and PK, PD of HPG1860 in Healthy Subjects</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo Controlled, Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HPG1860</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hepagene (Shanghai) Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hepagene (Shanghai) Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, placebo-controlled, single and multiple ascending dose&#xD;
      Phase 1study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and&#xD;
      food effect of HPG1860 orally administered in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In SAD and MAD studies, all subjects are randomized in a 3:1 ratio. In SAD study , there are&#xD;
      6 cohorts (8 subjects/cohort) with dose levels of 10mg, 20 mg, 40 mg, 80 mg, 120 mg and 150&#xD;
      mg respectively. Blood samples will be collected for safety, PK and PD assessments. After the&#xD;
      completion of Cohort 2 (20 mg) in SAD study, following a 7-day washout period, the same 8&#xD;
      subjects will receive another single oral dose of 20 mg HPG1860 after a standard high&#xD;
      fat/high calorie breakfast (the fed condition). PK blood samplings will be collected and Cmax&#xD;
      and AUC will be used for assessing the food effect. In MAD study, there are 3 cohorts (8&#xD;
      subjects/cohort) with dose levels of 10mg, 30mg and 90 mg, respectively and dosing regimen is&#xD;
      once daily for 14 consecutive days. Blood samples will be collected for safety, PK and PD&#xD;
      assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2019</start_date>
  <completion_date type="Actual">August 7, 2021</completion_date>
  <primary_completion_date type="Actual">November 25, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Part 1 SAD: 6 cohorts Part 2 MAD: 3 cohorts</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>After single ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts</measure>
    <time_frame>Day1-8</time_frame>
    <description>To investigate the safety and tolerability of orally administered SAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>After multiple ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts</measure>
    <time_frame>Day1-21</time_frame>
    <description>To investigate the safety and tolerability of orally administered MAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of HPG1860 on Blood Concentration of FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4)</measure>
    <time_frame>SAD: Day 1. MAD: Day 1 and Day14</time_frame>
    <description>To assess blood FGF19 and C4 changes vs placebo after orally administered SAD and MAD of HPG1860</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>SAD: up to 48 hours ; MAD: up to 14 days.</time_frame>
    <description>Maximum observed serum concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>SAD: up to 48 hours ; MAD: up to 14 days.</time_frame>
    <description>Time to reach Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast</measure>
    <time_frame>SAD: up to 48 hours ; MAD: up to 14 days.</time_frame>
    <description>Area under the curve from the time of dosing to the time of the last measurable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf</measure>
    <time_frame>SAD: up to 48 hours ; MAD: up to 14 days.</time_frame>
    <description>Area under the curve from the time of dosing extrapolated to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL</measure>
    <time_frame>SAD: up to 48 hours; MAD: up to 14 days</time_frame>
    <description>Apparent total body clearance of the drug from plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vd</measure>
    <time_frame>SAD: up to 48 hours; MAD: up to 14 days</time_frame>
    <description>Apparent volume of distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Food on Cmax of HPG1860</measure>
    <time_frame>up to 48 hours</time_frame>
    <description>To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Food on AUCinf of HPG1860</measure>
    <time_frame>up to 48 hours</time_frame>
    <description>To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUCinf</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Food on AUC0-24h of HPG1860</measure>
    <time_frame>24 hours</time_frame>
    <description>To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUC0-24h</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>SAD 10mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 10 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD 20mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 20 mg. Food effect will also be assessed at the same dose level.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD 40mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 40mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD 80 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 80 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD 120 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 120 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAD 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 150 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD 10mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose regimen is once daily 10 mg for 14 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD 30mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose regimen is once daily 30 mg for 14 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAD 90 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose regimen is once daily 90mg for 14 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HPG1860</intervention_name>
    <description>6 subjects randomized to active compound and 2 subjects randomized to placebo</description>
    <arm_group_label>MAD 10mg</arm_group_label>
    <arm_group_label>MAD 30mg</arm_group_label>
    <arm_group_label>MAD 90 mg</arm_group_label>
    <arm_group_label>SAD 10mg</arm_group_label>
    <arm_group_label>SAD 120 mg</arm_group_label>
    <arm_group_label>SAD 150 mg</arm_group_label>
    <arm_group_label>SAD 20mg</arm_group_label>
    <arm_group_label>SAD 40mg</arm_group_label>
    <arm_group_label>SAD 80 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy subjects aged 18-55 years old (inclusive), male or female&#xD;
&#xD;
          2. Females must be of non-childbearing potential&#xD;
&#xD;
          3. Have a body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive) and weigh at&#xD;
             least 50 kg at time of Screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal,&#xD;
             endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic,&#xD;
             immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the&#xD;
             Investigator&#xD;
&#xD;
          2. Taken an investigational drug within 3 months or 5 half-live, whichever is longer from&#xD;
             the Screening date&#xD;
&#xD;
          3. Any liver function panel analyte (LFT) value &gt; upper limits of normal reference range&#xD;
&#xD;
          4. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B core (IgG&#xD;
             and IgM) and surface antigen (HBsAg), Hepatitis A antibody (IgM), hepatitis C antibody&#xD;
             (IgG), or hepatitis E (IgG and IgM) at Screening&#xD;
&#xD;
          5. Any condition or finding that in the opinion of the Principal Investigator or designee&#xD;
             would put the subject or study conduct at risk if the subject were to participate in&#xD;
             the 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>
  <location>
    <facility>
      <name>Pharmaron CPC InC</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>April 22, 2022</last_update_submitted>
  <last_update_submitted_qc>April 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2022</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/NCT04480697
org study id: HPG1860-101
nct id: NCT04480697
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, double-blind, placebo-controlled, single and multiple ascending dose
      Phase 1study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and
      food effect of HPG1860 orally administered in healthy subjects.
In SAD and MAD studies, all subjects are randomized in a 3:1 ratio. In SAD study , there are
      6 cohorts (8 subjects/cohort) with dose levels of 10mg, 20 mg, 40 mg, 80 mg, 120 mg and 150
      mg respectively. Blood samples will be collected for safety, PK and PD assessments. After the
      completion of Cohort 2 (20 mg) in SAD study, following a 7-day washout period, the same 8
      subjects will receive another single oral dose of 20 mg HPG1860 after a standard high
      fat/high calorie breakfast (the fed condition). PK blood samplings will be collected and Cmax
      and AUC will be used for assessing the food effect. In MAD study, there are 3 cohorts (8
      subjects/cohort) with dose levels of 10mg, 30mg and 90 mg, respectively and dosing regimen is
      once daily for 14 consecutive days. Blood samples will be collected for safety, PK and PD
      assessments.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Part 1 SAD: 6 cohorts Part 2 MAD: 3 cohorts
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: After single ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts
time frame: Day1-8
description: To investigate the safety and tolerability of orally administered SAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.
measure: After multiple ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts
time frame: Day1-21
description: To investigate the safety and tolerability of orally administered MAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.
measure: Effect of HPG1860 on Blood Concentration of FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4)
time frame: SAD: Day 1. MAD: Day 1 and Day14
description: To assess blood FGF19 and C4 changes vs placebo after orally administered SAD and MAD of HPG1860
measure: Cmax
time frame: SAD: up to 48 hours ; MAD: up to 14 days.
description: Maximum observed serum concentration
measure: Tmax
time frame: SAD: up to 48 hours ; MAD: up to 14 days.
description: Time to reach Cmax
measure: AUClast
time frame: SAD: up to 48 hours ; MAD: up to 14 days.
description: Area under the curve from the time of dosing to the time of the last measurable concentration
measure: AUCinf
time frame: SAD: up to 48 hours ; MAD: up to 14 days.
description: Area under the curve from the time of dosing extrapolated to infinity
measure: CL
time frame: SAD: up to 48 hours; MAD: up to 14 days
description: Apparent total body clearance of the drug from plasma
measure: Vd
time frame: SAD: up to 48 hours; MAD: up to 14 days
description: Apparent volume of distribution
measure: Effect of Food on Cmax of HPG1860
time frame: up to 48 hours
description: To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating Cmax
measure: Effect of Food on AUCinf of HPG1860
time frame: up to 48 hours
description: To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUCinf
measure: Effect of Food on AUC0-24h of HPG1860
time frame: 24 hours
description: To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUC0-24h
arm group label: SAD 10mg
arm group type: Experimental
description: A single oral dose of 10 mg
arm group label: SAD 20mg
arm group type: Experimental
description: A single oral dose of 20 mg. Food effect will also be assessed at the same dose level.
arm group label: SAD 40mg
arm group type: Experimental
description: A single oral dose of 40mg
arm group label: SAD 80 mg
arm group type: Experimental
description: A single oral dose of 80 mg
arm group label: SAD 120 mg
arm group type: Experimental
description: A single oral dose of 120 mg
arm group label: SAD 150 mg
arm group type: Experimental
description: A single oral dose of 150 mg
arm group label: MAD 10mg
arm group type: Experimental
description: Dose regimen is once daily 10 mg for 14 consecutive days.
arm group label: MAD 30mg
arm group type: Experimental
description: Dose regimen is once daily 30 mg for 14 consecutive days.
arm group label: MAD 90 mg
arm group type: Experimental
description: Dose regimen is once daily 90mg for 14 consecutive days.
intervention type: Drug
intervention name: HPG1860
description: 6 subjects randomized to active compound and 2 subjects randomized to placebo
arm group label: MAD 10mg
arm group label: MAD 30mg
arm group label: MAD 90 mg
arm group label: SAD 10mg
arm group label: SAD 120 mg
arm group label: SAD 150 mg
arm group label: SAD 20mg
arm group label: SAD 40mg
arm group label: SAD 80 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor