<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/NCT04480827</url>
  </required_header>
  <id_info>
    <org_study_id>Aramchol-019</org_study_id>
    <nct_id>NCT04480827</nct_id>
  </id_info>
  <brief_title>Open-Label Study to Evaluate the Safety, Tolerability, and PK of Aramchol in Subjects With Hepatic Impairment</brief_title>
  <official_title>A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Aramchol in Subjects With Hepatic Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Galmed Research and Development, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Galmed Pharmaceuticals 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>
      Phase 1, multicenter, open-label, 2-part, single- and multiple-dose study designed to assess&#xD;
      the effect of hepatic insufficiency on the PK of aramchol&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Each of the 2 parts of the study will consist of a screening period, a check in day, a&#xD;
      treatment period, and an end of study (EOS) visit.&#xD;
&#xD;
      In Part 1 (single-dose): up to 48 subjects are planned: 8 subjects each in the mild (Cohort&#xD;
      A), moderate (Cohort B), and severe (Cohort C) hepatic impairment cohorts and 8 to 24 healthy&#xD;
      control subjects with normal hepatic function (Cohort D). Enrollment of 8 subjects with mild&#xD;
      hepatic impairment (Cohort A) will proceed only if there is evidence of reduced clearance of&#xD;
      aramchol in Cohort B. Assignment to cohorts A to C, will be according to Child Pugh&#xD;
      classification system.&#xD;
&#xD;
      Serial blood samples for PK analysis of aramchol concentrations in plasma will be collected&#xD;
      before dosing (0 hour) and up to 168 hours for healthy subjects and 240 hours for hepatically&#xD;
      impaired subjects after administration of aramchol.&#xD;
&#xD;
      In Part 2 (multiple-dose), a cohort of at least 8 subjects comprising of mild, moderate or&#xD;
      severe hepatic impaired subjects, as well as a cohort of up to 8 healthy volunteers will be&#xD;
      administered aramchol as multiple doses to obtain the PK profile of aramchol at steady state.&#xD;
      Aramchol will be given twice daily for 12 days. Trough blood samples for analysis of aramchol&#xD;
      plasma concentrations will be collected before the AM dose on several days and at intervals&#xD;
      to 12 hours after the AM dose on Day 12.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">January 22, 2020</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">June 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Oral Clearance, single dose</measure>
    <time_frame>Day 11</time_frame>
    <description>CL/F measured after single dose during part 1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral Clearance, steady state</measure>
    <time_frame>Day 12</time_frame>
    <description>CL/F measured at steady state during part 2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-tau, steady state</measure>
    <time_frame>Day 12</time_frame>
    <description>AUC from time 0 to the dosing interval tau measured at steady state during part 2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant TEAEs that are considered related to treatment as assessed by CTCAE v4.0</measure>
    <time_frame>Part 1: up to 22 days; Part 2: up to 27 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant changes in liver function tests</measure>
    <time_frame>Part 1: up to 22 days; Part 2: up to 27 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECG QTc interval using Fridericia correction</measure>
    <time_frame>Part 1: up to 22 days; Part 2: up to 27 days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Part 1: Mild Hepatic Impairment (Cohort A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 mild hepatic impaired subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Moderate Hepatic Impairment (Cohort B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 moderate hepatic impaired subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Severe Hepatic Impairment (Cohort C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 severe hepatic impaired subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Healthy Volunteers (Cohort D)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>up to 24 matched healthy volunteers</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Hepatic Impairment cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>up to 8 hepatic impaired subjects (mild, moderate or severe)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Healthy Volunteers cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>up to 8 matched healthy volunteers</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aramchol 600mg single dose</intervention_name>
    <description>aramchol acid tablet 600mg, single dose</description>
    <arm_group_label>Part 1: Healthy Volunteers (Cohort D)</arm_group_label>
    <arm_group_label>Part 1: Mild Hepatic Impairment (Cohort A)</arm_group_label>
    <arm_group_label>Part 1: Moderate Hepatic Impairment (Cohort B)</arm_group_label>
    <arm_group_label>Part 1: Severe Hepatic Impairment (Cohort C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aramchol 300mg, bid</intervention_name>
    <description>aramchol acid tablet 300mg, bid for 12 days</description>
    <arm_group_label>Part 2: Healthy Volunteers cohort</arm_group_label>
    <arm_group_label>Part 2: Hepatic Impairment cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is male or female 18 to 79 years of age, inclusive.&#xD;
&#xD;
          2. The subject has a body mass index of 19 to 40 kg/m2, inclusive, at screening.&#xD;
&#xD;
          3. Females of childbearing potential must practice a highly effective method of&#xD;
             contraception throughout the study period and for 1 month after treatment&#xD;
             discontinuation.&#xD;
&#xD;
          4. Male subjects with female partners of childbearing potential must be vasectomized, be&#xD;
             willing to use an acceptable method of birth control, or practice abstinence during&#xD;
             the study.&#xD;
&#xD;
          5. The subject has a resting pulse rate of ≥40 and &lt;100 beats per minute with no&#xD;
             clinically significant deviation as judged by the investigator.&#xD;
&#xD;
          6. The subject has a QT interval corrected for heart rate using Fridericia's formula of&#xD;
             &lt;500 msec.&#xD;
&#xD;
          7. The subject agrees to comply with all protocol requirements.&#xD;
&#xD;
          8. The subject is able to provide written informed consent.&#xD;
&#xD;
             Additional Inclusion Criteria for Healthy Subjects Only (Cohort D):&#xD;
&#xD;
          9. The subject has normal hepatic function.&#xD;
&#xD;
         10. The subject has a resting blood pressure of 90 to 150 mm Hg (systolic) and 50 to 100&#xD;
             mm Hg (diastolic).&#xD;
&#xD;
         11. The subject is judged by the investigator to be in good general health, as determined&#xD;
             by medical history, clinical laboratory assessments, vital sign measurements, 12 lead&#xD;
             electrocardiogram (ECG) results, and physical examination findings.&#xD;
&#xD;
             Additional Inclusion Criteria for Subjects With Hepatic Impairment Only (Cohorts A, B,&#xD;
             and C):&#xD;
&#xD;
         12. The subject has cirrhosis with evidence of impaired liver function. The etiology of&#xD;
             the cirrhosis may be alcoholic, autoimmune, nonalcoholic steatohepatitis, or chronic&#xD;
             viral hepatitis type B or C.&#xD;
&#xD;
         13. The subject has chronic (more than 6 months) and stable hepatic impairment (ie, no&#xD;
             acute episodes of illness within 30 days before screening due to deterioration of&#xD;
             hepatic function) as assessed by a Child-Pugh classification score of mild (5 to 6&#xD;
             points), moderate (7 to 9 points), or severe (10 to 15 points).&#xD;
&#xD;
         14. The subject has a resting blood pressure of 90 to 155 mm Hg (systolic) and 50 to 100&#xD;
             mm Hg (diastolic).&#xD;
&#xD;
         15. The subject is judged by the investigator to be in good general health, as determined&#xD;
             by medical history, clinical laboratory assessments, vital sign measurements, 12 lead&#xD;
             ECG results, and physical examination findings, except for findings that, as judged by&#xD;
             the investigator, are consistent with the subject's hepatic impairment or other stable&#xD;
             concomitant medical conditions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The subject has a history or clinical manifestations of a significant neurological,&#xD;
             renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or&#xD;
             psychiatric disease that would preclude study participation, as judged by the&#xD;
             investigator.&#xD;
&#xD;
          2. The subject has a positive test result for human immunodeficiency virus type 1 or 2&#xD;
             antibodies at screening.&#xD;
&#xD;
          3. The subject has a history of drug abuse within 3 months before screening.&#xD;
&#xD;
          4. The subject has a history of alcoholism within 3 months before screening, or excessive&#xD;
             alcohol consumption (regular alcohol intake &gt;15 units per week) (1 unit is equal to&#xD;
             approximately ½ pint [200 mL] of beer, 1 small glass [100 mL] of wine, or 1 measure&#xD;
             [25 mL] of spirits).&#xD;
&#xD;
          5. The subject smokes &gt;10 cigarettes daily and is unwilling to reduce to &lt;5 daily from&#xD;
             the time of screening through the last PK sample.&#xD;
&#xD;
          6. The subject is unable or unwilling to abstain from alcohol, caffeine, xanthine&#xD;
             containing beverages or food (eg, coffee, tea, chocolate, and caffeinated sodas,&#xD;
             colas), grapefruit, grapefruit juice, Seville oranges, or products containing any of&#xD;
             these, from 48 hours prior to study drug dosing until discharge.&#xD;
&#xD;
          7. The subject is involved in strenuous activity or contact sports within 24 hours of the&#xD;
             first dose of study drug or during the study.&#xD;
&#xD;
          8. The subject has donated blood or blood products &gt;450 mL within 3 months before the&#xD;
             first dose of study drug.&#xD;
&#xD;
          9. The subject has a presence or history of relevant drug and/or food allergies (ie,&#xD;
             allergy to aramchol, cholic acid, or any excipients, or any significant food allergy.&#xD;
&#xD;
         10. The subject has received study drug in another investigational study within 30 days of&#xD;
             dosing.&#xD;
&#xD;
         11. In the opinion of the investigator, the subject is not suitable for entry into the&#xD;
             study.&#xD;
&#xD;
        For additional exclusion criteria specific to hepatic impaired subjects and healthy&#xD;
        volunteers, see protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 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 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholic Acids</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>September 20, 2022</submitted>
    <returned>August 3, 2023</returned>
    <submitted>August 8, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04480827
org study id: Aramchol-019
nct id: NCT04480827
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Phase 1, multicenter, open-label, 2-part, single- and multiple-dose study designed to assess
      the effect of hepatic insufficiency on the PK of aramchol
Each of the 2 parts of the study will consist of a screening period, a check in day, a
      treatment period, and an end of study (EOS) visit.

      In Part 1 (single-dose): up to 48 subjects are planned: 8 subjects each in the mild (Cohort
      A), moderate (Cohort B), and severe (Cohort C) hepatic impairment cohorts and 8 to 24 healthy
      control subjects with normal hepatic function (Cohort D). Enrollment of 8 subjects with mild
      hepatic impairment (Cohort A) will proceed only if there is evidence of reduced clearance of
      aramchol in Cohort B. Assignment to cohorts A to C, will be according to Child Pugh
      classification system.

      Serial blood samples for PK analysis of aramchol concentrations in plasma will be collected
      before dosing (0 hour) and up to 168 hours for healthy subjects and 240 hours for hepatically
      impaired subjects after administration of aramchol.

      In Part 2 (multiple-dose), a cohort of at least 8 subjects comprising of mild, moderate or
      severe hepatic impaired subjects, as well as a cohort of up to 8 healthy volunteers will be
      administered aramchol as multiple doses to obtain the PK profile of aramchol at steady state.
      Aramchol will be given twice daily for 12 days. Trough blood samples for analysis of aramchol
      plasma concentrations will be collected before the AM dose on several days and at intervals
      to 12 hours after the AM dose on Day 12.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Oral Clearance, single dose
time frame: Day 11
description: CL/F measured after single dose during part 1
measure: Oral Clearance, steady state
time frame: Day 12
description: CL/F measured at steady state during part 2
measure: AUC0-tau, steady state
time frame: Day 12
description: AUC from time 0 to the dosing interval tau measured at steady state during part 2
measure: Number of subjects with clinically significant TEAEs that are considered related to treatment as assessed by CTCAE v4.0
time frame: Part 1: up to 22 days; Part 2: up to 27 days
measure: Number of subjects with clinically significant changes in liver function tests
time frame: Part 1: up to 22 days; Part 2: up to 27 days
measure: ECG QTc interval using Fridericia correction
time frame: Part 1: up to 22 days; Part 2: up to 27 days
arm group label: Part 1: Mild Hepatic Impairment (Cohort A)
arm group type: Experimental
description: 8 mild hepatic impaired subjects
arm group label: Part 1: Moderate Hepatic Impairment (Cohort B)
arm group type: Experimental
description: 8 moderate hepatic impaired subjects
arm group label: Part 1: Severe Hepatic Impairment (Cohort C)
arm group type: Experimental
description: 8 severe hepatic impaired subjects
arm group label: Part 1: Healthy Volunteers (Cohort D)
arm group type: Experimental
description: up to 24 matched healthy volunteers
arm group label: Part 2: Hepatic Impairment cohort
arm group type: Experimental
description: up to 8 hepatic impaired subjects (mild, moderate or severe)
arm group label: Part 2: Healthy Volunteers cohort
arm group type: Experimental
description: up to 8 matched healthy volunteers
intervention type: Drug
intervention name: Aramchol 600mg single dose
description: aramchol acid tablet 600mg, single dose
arm group label: Part 1: Healthy Volunteers (Cohort D)
arm group label: Part 1: Mild Hepatic Impairment (Cohort A)
arm group label: Part 1: Moderate Hepatic Impairment (Cohort B)
arm group label: Part 1: Severe Hepatic Impairment (Cohort C)
intervention type: Drug
intervention name: Aramchol 300mg, bid
description: aramchol acid tablet 300mg, bid for 12 days
arm group label: Part 2: Healthy Volunteers cohort
arm group label: Part 2: Hepatic Impairment cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Cholic Acids
submitted: September 20, 2022
returned: August 3, 2023
submitted: August 8, 2023