<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/NCT03801759</url>
  </required_header>
  <id_info>
    <org_study_id>AKB-6548-CI-0031</org_study_id>
    <nct_id>NCT03801759</nct_id>
  </id_info>
  <brief_title>Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide</brief_title>
  <official_title>A Phase 1 Open-label, Three Arm Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug-Interactions With Digoxin, Adefovir and Furosemide</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>Yes</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 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a&#xD;
      perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy&#xD;
      male and female subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a&#xD;
      perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy&#xD;
      male and female subjects. Unique subjects will be enrolled into each arm of the study and&#xD;
      enrollment will be sequential. The first 20 subjects confirmed to be eligible will be&#xD;
      assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and&#xD;
      the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis&#xD;
      will be collected at pre-defined timepoints for each arm throughout the study. Subjects will&#xD;
      be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic&#xD;
      period, and a 30-day follow up period post last dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2018</start_date>
  <completion_date type="Actual">September 30, 2018</completion_date>
  <primary_completion_date type="Actual">September 30, 2018</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Each arm has fixed sequence design.&#xD;
Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat&#xD;
Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat&#xD;
Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustat</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination rate constant (Kel) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t½) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects</measure>
    <time_frame>Up to 12 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Drug Interaction Potentiation</condition>
  <arm_group>
    <arm_group_label>Vadadustat, digoxin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vadadustat, adefovir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vadadustat, Furosemide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vadadustat</intervention_name>
    <description>Oral dose 600 mg</description>
    <arm_group_label>Vadadustat, Furosemide</arm_group_label>
    <arm_group_label>Vadadustat, adefovir</arm_group_label>
    <arm_group_label>Vadadustat, digoxin</arm_group_label>
    <other_name>AKB 6548</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide</intervention_name>
    <description>Oral Furosemide</description>
    <arm_group_label>Vadadustat, Furosemide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adefovir</intervention_name>
    <description>Oral Adefovir</description>
    <arm_group_label>Vadadustat, adefovir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin</intervention_name>
    <description>Oral Digoxin</description>
    <arm_group_label>Vadadustat, digoxin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy Male or female between 18 and 55 years of age, inclusive, at time of informed&#xD;
             consent.&#xD;
&#xD;
          -  Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for&#xD;
             females and 50 kg for males, inclusive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or past clinically significant history of cardiovascular, cerebrovascular,&#xD;
             pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic,&#xD;
             urologic, neurologic, dermatologic, psychiatric, or other major disease. History of&#xD;
             cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within&#xD;
             5 years prior to Screening.&#xD;
&#xD;
          -  Positive test results for human immunodeficiency virus (HIV) antibody; Positive test&#xD;
             results of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody&#xD;
             (HCVab) within 3 months prior to screening; or positive test results for human&#xD;
             immunodeficiency virus antibody (HIVab) at Screening&#xD;
&#xD;
          -  Taking any prescription medication or over the counter multi-vitamin supplement, or&#xD;
             any non-prescription products (including herbal-containing preparations but excluding&#xD;
             acetaminophen) within 14 days prior to Day -1.&#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>Akebia Therapeutics</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>inVentiv Health Clinique Inc.</name>
      <address>
        <city>Québec City</city>
        <state>Quebec</state>
        <zip>G1P 0A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</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 11, 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>vadadustat</keyword>
  <keyword>drug interactions</keyword>
  <keyword>healthy volunteers</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adefovir</mesh_term>
    <mesh_term>Digoxin</mesh_term>
    <mesh_term>Furosemide</mesh_term>
  </intervention_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/NCT03801759
org study id: AKB-6548-CI-0031
nct id: NCT03801759
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a
      perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy
      male and female subjects.
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a
      perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy
      male and female subjects. Unique subjects will be enrolled into each arm of the study and
      enrollment will be sequential. The first 20 subjects confirmed to be eligible will be
      assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and
      the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis
      will be collected at pre-defined timepoints for each arm throughout the study. Subjects will
      be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic
      period, and a 30-day follow up period post last dose.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Each arm has fixed sequence design.
Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat
Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat
Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustat
primary purpose: Basic Science
masking: None (Open Label)
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Elimination rate constant (Kel) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Terminal half-life (t½) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide
time frame: Up to 12 Weeks
measure: Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects
time frame: Up to 12 Weeks
arm group label: Vadadustat, digoxin
arm group type: Experimental
description: Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg.
arm group label: Vadadustat, adefovir
arm group type: Experimental
description: Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir.
arm group label: Vadadustat, Furosemide
arm group type: Experimental
description: Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg.
intervention type: Drug
intervention name: Vadadustat
description: Oral dose 600 mg
arm group label: Vadadustat, Furosemide
arm group label: Vadadustat, adefovir
arm group label: Vadadustat, digoxin
other name: AKB 6548
intervention type: Drug
intervention name: Furosemide
description: Oral Furosemide
arm group label: Vadadustat, Furosemide
intervention type: Drug
intervention name: Adefovir
description: Oral Adefovir
arm group label: Vadadustat, adefovir
intervention type: Drug
intervention name: Digoxin
description: Oral Digoxin
arm group label: Vadadustat, digoxin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Akebia Therapeutics
role: Study Director
affiliation: Sponsor GmbH
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Adefovir
mesh term: Digoxin
mesh term: Furosemide
sharing ipd: Undecided