<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/NCT03799848</url>
  </required_header>
  <id_info>
    <org_study_id>AKB-6548-CI-0024</org_study_id>
    <nct_id>NCT03799848</nct_id>
  </id_info>
  <brief_title>A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function</brief_title>
  <official_title>Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akebia Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Akebia Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <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 Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single&#xD;
      oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched&#xD;
      control subjects with normal hepatic function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile,&#xD;
      safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic&#xD;
      impairment relative to control subjects with normal hepatic function. The study will enroll&#xD;
      up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK&#xD;
      and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24,&#xD;
      36, 48, 60, and 72 hours post-dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 12, 2018</start_date>
  <completion_date type="Actual">October 18, 2018</completion_date>
  <primary_completion_date type="Actual">October 18, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve from dosing to last measurable concentration (AUClast)</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve from dosing to infinity (AUCinf)</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Observed maximum concentration (Cmax).</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax of vadadustat</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F) of vadadustat</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (Vd/F) of vadadustat</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2) of vadadustat</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach Tmax of vadadustat</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects</measure>
    <time_frame>Up to 9 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax related to free drug (Cmax, free) of Vadadustat Unbound</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast related to free drug (AUClast, free) of Vadadustat Unbound</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F related to free drug (CL/Ffree) of Vadadustat Unbound</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2) of Vadadustat Unbound</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax of vadadustat metabolites</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2) of Vadadustat metabolites</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance (CLr) of Vadadustat/metabolite(s) Urine</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine</measure>
    <time_frame>Day 1, Day 4</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Vadadustat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vadadustat</intervention_name>
    <description>Oral tablet</description>
    <arm_group_label>Vadadustat</arm_group_label>
    <other_name>AKB-6548</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (All groups):&#xD;
&#xD;
          -  Male or female subjects between ≥18 years and ≤70 years of age&#xD;
&#xD;
          -  Have a body weight ≥45 kg and body mass index (BMI) ≥18.5 kg/m2 to 40.0 kg/m2&#xD;
&#xD;
        Additional Group-Specific Inclusion Criteria:&#xD;
&#xD;
          -  Group 1 (Moderate Hepatic Impairment Subjects):&#xD;
&#xD;
               -  Presence of Moderate hepatic impairment (Child-Pugh Class B)&#xD;
&#xD;
          -  Group 2 (Normal Hepatic Function Subjects):&#xD;
&#xD;
               -  Normal hepatic function&#xD;
&#xD;
          -  Group 3 (Mild Hepatic Impairment Subjects):&#xD;
&#xD;
               -  Presence of mild hepatic impairment ( Child-Pugh Class A)&#xD;
&#xD;
        Exclusion Criteria (all groups):&#xD;
&#xD;
          -  Renal impairment ≥ Stage 3 (estimated glomerular filtration rate [eGFR] &lt;60&#xD;
             mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation)&#xD;
&#xD;
          -  Any history of active malignancy within 2 years prior to or during screening, except&#xD;
             for treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma&#xD;
             of skin, or cervical carcinoma in situ; any history of tuberculosis and/or prophylaxis&#xD;
             for tuberculosis&#xD;
&#xD;
          -  Positive test for human immunodeficiency virus (HIV) antibody at Screening.&#xD;
&#xD;
          -  Hepatic or other organ or cell transplant&#xD;
&#xD;
          -  Subjects with alcoholic cirrhosis must be sober for a minimum of 6 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Akebia Therapeutics</last_name>
    <role>Study Director</role>
    <affiliation>Akebia Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Clinical Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Research Corporation at the University of Texas Liver Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>March 20, 2019</last_update_submitted>
  <last_update_submitted_qc>March 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatic impairment</keyword>
  <keyword>Healthy subjects</keyword>
  <keyword>Child-pugh</keyword>
  <keyword>Vadadustat</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03799848
org study id: AKB-6548-CI-0024
nct id: NCT03799848
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single
      oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched
      control subjects with normal hepatic function.
This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile,
      safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic
      impairment relative to control subjects with normal hepatic function. The study will enroll
      up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK
      and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24,
      36, 48, 60, and 72 hours post-dose.
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Area under the concentration-time curve from dosing to last measurable concentration (AUClast)
time frame: Day 1, Day 4
measure: Area under the concentration-time curve from dosing to infinity (AUCinf)
time frame: Day 1, Day 4
measure: Observed maximum concentration (Cmax).
time frame: Day 1, Day 4
measure: Time to reach Cmax of vadadustat
time frame: Day 1, Day 4
measure: Apparent total body clearance (CL/F) of vadadustat
time frame: Day 1, Day 4
measure: Apparent volume of distribution (Vd/F) of vadadustat
time frame: Day 1, Day 4
measure: Terminal half-life (t1/2) of vadadustat
time frame: Day 1, Day 4
measure: Time to reach Tmax of vadadustat
time frame: Day 1, Day 4
measure: Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects
time frame: Up to 9 Weeks
measure: Cmax related to free drug (Cmax, free) of Vadadustat Unbound
time frame: Day 1, Day 4
measure: AUClast related to free drug (AUClast, free) of Vadadustat Unbound
time frame: Day 1, Day 4
measure: AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound
time frame: Day 1, Day 4
measure: CL/F related to free drug (CL/Ffree) of Vadadustat Unbound
time frame: Day 1, Day 4
measure: Terminal half-life (t1/2) of Vadadustat Unbound
time frame: Day 1, Day 4
measure: The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites
time frame: Day 1, Day 4
measure: The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite
time frame: Day 1, Day 4
measure: Time to reach Cmax of vadadustat metabolites
time frame: Day 1, Day 4
measure: Terminal half-life (t1/2) of Vadadustat metabolites
time frame: Day 1, Day 4
measure: Renal clearance (CLr) of Vadadustat/metabolite(s) Urine
time frame: Day 1, Day 4
measure: Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine
time frame: Day 1, Day 4
measure: Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine
time frame: Day 1, Day 4
arm group label: Vadadustat
arm group type: Experimental
description: Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A)
intervention type: Drug
intervention name: Vadadustat
description: Oral tablet
arm group label: Vadadustat
other name: AKB-6548
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Akebia Therapeutics
role: Study Director
affiliation: Akebia Therapeutics
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
sharing ipd: Undecided