<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/NCT04481594</url>
  </required_header>
  <id_info>
    <org_study_id>HPN-01-US-101</org_study_id>
    <nct_id>NCT04481594</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety and Tolerability of Single and Multiple Ascending Doses of HPN-01 in Healthy Subjects</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo Controlled, Sequential Parallel Group, Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HPN-01</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hepanova Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hepanova Inc.</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 study is a randomized, double-blind, placebo-controlled first-in-human study in which&#xD;
      the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered HPN-01&#xD;
      will be evaluated in healthy subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims to obtain safety, tolerability, pharmacokinetic and pharmacodynamic data when&#xD;
      HPN-01 is orally administered as single doses and as multiple doses to healthy subjects.&#xD;
&#xD;
      The study will be conducted in 2 parts: a single ascending dose (SAD) phase (Part 1) and a&#xD;
      multiple ascending dose (MAD) phase (Part 2). One cohort of Part 1 will receive HPN-01 after&#xD;
      a standard high fat/high calorie breakfast (the fed condition) to investigate the effect of&#xD;
      food on the pharmacokinetics of HPN-01.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 8, 2020</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">July 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>Sequential Assignment</intervention_model>
    <intervention_model_description>Parallel Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>double-blind (participant, investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Single-dose PK Parameter</measure>
    <time_frame>Up to 72 hours postdose</time_frame>
    <description>Cmax of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Single-dose PK Parameter</measure>
    <time_frame>Up to 72 hours postdose</time_frame>
    <description>AUClast of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Single-dose PK Parameter</measure>
    <time_frame>Up to 72 hours postdose</time_frame>
    <description>AUCinf of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple-dose PK Parameters</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
    <description>Cmax of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple-dose PK Parameters</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
    <description>Ctau of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple-dose PK Parameters</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
    <description>AUCtau of HPN-01</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>Up to 15 days plus 6 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants with 12-lead ECG Abnormalities</measure>
    <time_frame>Up to 15 days plus 6 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants with Clinical Laboratory Abnormalities</measure>
    <time_frame>Up to 15 days plus 6 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of PD Biomarker Level of Fibroblast Growth Factor 19 (FGF19) Following Oral Single and Multiple Ascending Dose Administration</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of PD Biomarker Level of C4 Following Oral Single and Multiple Ascending Dose Administration</measure>
    <time_frame>Up to 24 hours postdose</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Non-Alcoholic Steatohepatitis (NASH)</condition>
  <arm_group>
    <arm_group_label>HPN-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1: Including 6 dose cohorts (25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg). Each dose cohort will receive a single dose of HPN-01. One cohort of Part 1 will receive HPN-01 after a standard high fat/high calorie breakfast (the fed condition) to investigate the effect of food on the pharmacokinetics of HPN-01.&#xD;
Part 2: Including 3 dose cohorts (50 mg, 100 mg and 200 mg). Each dose cohort will receive HPN-01 once daily for a consecutive 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Part 1: Including 6 dose cohorts (25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg). Each dose cohort will receive a single dose of HPN-01 placebo.&#xD;
Part 2: Including 3 dose cohorts (50 mg, 100 mg and 200 mg). Each dose cohort will receive HPN-01 placebo once daily for a consecutive 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HPN-01</intervention_name>
    <description>25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg HPN-01 capsules</description>
    <arm_group_label>HPN-01</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg HPN-01 placebo capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Are capable of giving informed consent and complying with study procedures;&#xD;
&#xD;
          2. Are between the ages of 18 and 55 years, inclusive;&#xD;
&#xD;
          3. Female subjects have a negative pregnancy test result at screening and admission to&#xD;
             the study site, and meet one of the following criteria:&#xD;
&#xD;
               1. Using a medically acceptable form of birth control for at least 1 month prior to&#xD;
                  screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral,&#xD;
                  patch, injectable or vaginal ring), implantable device (implantable rod or&#xD;
                  intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral,&#xD;
                  patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)]&#xD;
&#xD;
               2. Surgically sterile for at least 3 months prior to screening by one of the&#xD;
                  following means:&#xD;
&#xD;
                    -  Bilateral tubal ligation&#xD;
&#xD;
                    -  Bilateral salpingectomy (with or without oophorectomy)&#xD;
&#xD;
                    -  Surgical hysterectomy&#xD;
&#xD;
                    -  Bilateral oophorectomy (with or without hysterectomy)&#xD;
&#xD;
               3. Postmenopausal, defined as the following:&#xD;
&#xD;
                    -  Last menstrual period greater than 12 months prior to screening&#xD;
&#xD;
                    -  Postmenopausal status confirmed by serum FSH and estradiol levels at&#xD;
                       screening;&#xD;
&#xD;
          4. Considered healthy by the Investigator, based on subject's reported medical history,&#xD;
             full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;&#xD;
&#xD;
          5. Normal renal function (eGFR &gt; 90 ml/min/1.75 m2) as determined by Investigator&#xD;
             following review of clinical laboratory test results;&#xD;
&#xD;
          6. Non-smoker and has not been exposed to any products containing nicotine in the last 6&#xD;
             months;&#xD;
&#xD;
          7. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50&#xD;
             kg;&#xD;
&#xD;
          8. Willing and able to adhere to study restrictions and to be confined at the clinical&#xD;
             research center;&#xD;
&#xD;
          9. Male subjects must agree to utilize a highly effective method of contraception (condom&#xD;
             plus spermicide) during heterosexual intercourse from clinic admission until 12 weeks&#xD;
             following the end of study visit;&#xD;
&#xD;
         10. Male subjects with female partners of child-bearing potential must agree to use&#xD;
             condoms for the duration of the study and until 12 weeks after dosing with the study&#xD;
             drug and must refrain from donating sperm for this same period.&#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. Known or suspected malignancy;&#xD;
&#xD;
          3. Reported history of pancreatitis or gall stones;&#xD;
&#xD;
          4. Reported history of unexplained syncope, symptomatic hypotension or hypoglycemia;&#xD;
&#xD;
          5. Family history of long QTc syndrome;&#xD;
&#xD;
          6. History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or&#xD;
             intolerance;&#xD;
&#xD;
          7. Poor venous access;&#xD;
&#xD;
          8. 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;
          9. Donated or lost &gt;500 mL of blood in the previous 3 months prior to screening;&#xD;
&#xD;
         10. Taken an investigational drug or participated in a clinical trial within 3 months (or&#xD;
             5 half-lives) prior to first dose of study drug, whichever is longer;&#xD;
&#xD;
         11. Taken any prescription medications (with the exception of hormonal contraceptive)&#xD;
             within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;&#xD;
&#xD;
         12. Hospital admission or major surgery within 6 months prior to screening;&#xD;
&#xD;
         13. A history of prescription drug abuse, or illicit drug use within 9 months prior to&#xD;
             screening;&#xD;
&#xD;
         14. A history of alcohol abuse according to medical history (≥ 2 drinks per day for male&#xD;
             and ≥ 1 drink per day for female) within 9 months prior to screening;&#xD;
&#xD;
         15. A positive screen for alcohol, drugs of abuse at screening or admission;&#xD;
&#xD;
         16. An unwillingness or inability to comply with food and beverage restrictions during&#xD;
             study participation;&#xD;
&#xD;
         17. Use of over-the-counter (OTC) medication within 7 days, and/or herbal medications&#xD;
             (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to first&#xD;
             dose of study drug (Note: Use of acetaminophen at &lt; 2 g/day is permitted until 24&#xD;
             hours prior to dosing);&#xD;
&#xD;
         18. Any condition or finding that in the Investigators opinion would put the subject or&#xD;
             study conduct at risk if the subject were to participate in 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>
  <overall_contact>
    <last_name>Michelle Pluviose, MS</last_name>
    <phone>201-416-7763</phone>
    <email>mpluviose@frontagelab.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Annie Li, MD</last_name>
    <phone>201-416-7770</phone>
    <email>ali@frontagelab.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Frontage Clinical Services, Inc</name>
      <address>
        <city>Secaucus</city>
        <state>New Jersey</state>
        <zip>07094</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michelle Pluviose, MS</last_name>
      <phone>201-416-7763</phone>
      <email>mpluviose@frontagelab.com</email>
    </contact>
    <contact_backup>
      <last_name>Annie Li, MD</last_name>
      <phone>2014167770</phone>
      <email>ali@frontagelab.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>February 8, 2021</last_update_submitted>
  <last_update_submitted_qc>February 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 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>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04481594
org study id: HPN-01-US-101
nct id: NCT04481594
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is a randomized, double-blind, placebo-controlled first-in-human study in which
      the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered HPN-01
      will be evaluated in healthy subjects
This study aims to obtain safety, tolerability, pharmacokinetic and pharmacodynamic data when
      HPN-01 is orally administered as single doses and as multiple doses to healthy subjects.

      The study will be conducted in 2 parts: a single ascending dose (SAD) phase (Part 1) and a
      multiple ascending dose (MAD) phase (Part 2). One cohort of Part 1 will receive HPN-01 after
      a standard high fat/high calorie breakfast (the fed condition) to investigate the effect of
      food on the pharmacokinetics of HPN-01.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: double-blind (participant, investigator)
measure: Single-dose PK Parameter
time frame: Up to 72 hours postdose
description: Cmax of HPN-01
measure: Single-dose PK Parameter
time frame: Up to 72 hours postdose
description: AUClast of HPN-01
measure: Single-dose PK Parameter
time frame: Up to 72 hours postdose
description: AUCinf of HPN-01
measure: Multiple-dose PK Parameters
time frame: Up to 24 hours postdose
description: Cmax of HPN-01
measure: Multiple-dose PK Parameters
time frame: Up to 24 hours postdose
description: Ctau of HPN-01
measure: Multiple-dose PK Parameters
time frame: Up to 24 hours postdose
description: AUCtau of HPN-01
measure: Incidence of Adverse Events
time frame: Up to 15 days plus 6 days
measure: Proportion of Participants with 12-lead ECG Abnormalities
time frame: Up to 15 days plus 6 days
measure: Proportion of Participants with Clinical Laboratory Abnormalities
time frame: Up to 15 days plus 6 days
measure: Measurement of PD Biomarker Level of Fibroblast Growth Factor 19 (FGF19) Following Oral Single and Multiple Ascending Dose Administration
time frame: Up to 24 hours postdose
measure: Measurement of PD Biomarker Level of C4 Following Oral Single and Multiple Ascending Dose Administration
time frame: Up to 24 hours postdose
arm group label: HPN-01
arm group type: Experimental
description: Part 1: Including 6 dose cohorts (25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg). Each dose cohort will receive a single dose of HPN-01. One cohort of Part 1 will receive HPN-01 after a standard high fat/high calorie breakfast (the fed condition) to investigate the effect of food on the pharmacokinetics of HPN-01.
Part 2: Including 3 dose cohorts (50 mg, 100 mg and 200 mg). Each dose cohort will receive HPN-01 once daily for a consecutive 14 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Part 1: Including 6 dose cohorts (25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg). Each dose cohort will receive a single dose of HPN-01 placebo.
Part 2: Including 3 dose cohorts (50 mg, 100 mg and 200 mg). Each dose cohort will receive HPN-01 placebo once daily for a consecutive 14 days.
intervention type: Drug
intervention name: HPN-01
description: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg HPN-01 capsules
arm group label: HPN-01
intervention type: Drug
intervention name: Placebo
description: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg HPN-01 placebo capsules
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michelle Pluviose, MS
phone: 201-416-7763
email: mpluviose@frontagelab.com
last name: Annie Li, MD
phone: 201-416-7770
email: ali@frontagelab.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No