<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/NCT03789032</url>
  </required_header>
  <id_info>
    <org_study_id>AKB-6548-CI-0033</org_study_id>
    <nct_id>NCT03789032</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect of Rabeprazole on the Pharmacokinetics of Vadadustat</brief_title>
  <official_title>A Phase 1, Fixed Sequence, Open-label Study in Healthy Adult Subjects to Evaluate the Effect of Multiple Doses of Rabeprazole on the Pharmacokinetics of a Single Dose of Vadadustat</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 1, fixed sequence, open-label study to evaluate the effect of multiple oral&#xD;
      doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat 300 mg in healthy&#xD;
      male and female subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, fixed sequence, open-label study in healthy adult subjects to evaluate the&#xD;
      effect of multiple doses of rabeprazole on the pharmacokinetics of a single dose of&#xD;
      vadadustat in healthy male and female subjects. Approximately twenty (20) subjects, with at&#xD;
      least 30% female subjects, will be enrolled to ensure 18 evaluable subjects. Subjects will be&#xD;
      on study for up to 66 days, including a 28-day screening period, 9-day clinic period, and a&#xD;
      30-day follow- up period post last dose. Subjects who are confirmed eligible and receive at&#xD;
      least one dose of study drug will be considered enrolled in the study. Blood samples for PK&#xD;
      analysis will be collected at pre-defined time points throughout the study up to 48 hours&#xD;
      post administration of vadadustat.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 3, 2018</start_date>
  <completion_date type="Actual">November 19, 2018</completion_date>
  <primary_completion_date type="Actual">November 9, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a single arm fixed sequence study. Subjects will be administered vadadustat on day 1, rabeprazole on days 2 to 5, and vadadustat and rabeprazole on day 6.</intervention_model_description>
    <primary_purpose>Treatment</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 vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve from 0 to infinity (AUCinf) for vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) for vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed plasma concentration (Tmax) of vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination rate constant (Kel) of vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t½) of vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CL/F) of vadadustat</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat</measure>
    <time_frame>Baseline and end of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat-O-glucuronide</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) of vadadustat-O-glucuronide</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reporting of treatment emergent adverse event (TEAE) as reported by study subjects</measure>
    <time_frame>Up to 10 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Drug Interaction Potentiation</condition>
  <condition>Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>Rabeprazole and Vadadustat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive vadadustat 300 mg on day 1, rabeprazole 20 mg every 12 hours on days 2 through 5 and vadadustat 300 mg and rabeprazole on day 6</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vadadustat</intervention_name>
    <description>Vadadustat 300 mg</description>
    <arm_group_label>Rabeprazole and Vadadustat</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rabeprazole</intervention_name>
    <description>Oral Rabeprazole</description>
    <arm_group_label>Rabeprazole and Vadadustat</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>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</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>Rabeprazole</keyword>
  <keyword>Pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rabeprazole</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/NCT03789032
org study id: AKB-6548-CI-0033
nct id: NCT03789032
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, fixed sequence, open-label study to evaluate the effect of multiple oral
      doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat 300 mg in healthy
      male and female subjects.
This is a Phase 1, fixed sequence, open-label study in healthy adult subjects to evaluate the
      effect of multiple doses of rabeprazole on the pharmacokinetics of a single dose of
      vadadustat in healthy male and female subjects. Approximately twenty (20) subjects, with at
      least 30% female subjects, will be enrolled to ensure 18 evaluable subjects. Subjects will be
      on study for up to 66 days, including a 28-day screening period, 9-day clinic period, and a
      30-day follow- up period post last dose. Subjects who are confirmed eligible and receive at
      least one dose of study drug will be considered enrolled in the study. Blood samples for PK
      analysis will be collected at pre-defined time points throughout the study up to 48 hours
      post administration of vadadustat.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a single arm fixed sequence study. Subjects will be administered vadadustat on day 1, rabeprazole on days 2 to 5, and vadadustat and rabeprazole on day 6.
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for vadadustat
time frame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) for vadadustat
time frame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) for vadadustat
time frame: Up to 10 weeks
measure: Time to maximum observed plasma concentration (Tmax) of vadadustat
time frame: Up to 10 weeks
measure: Elimination rate constant (Kel) of vadadustat
time frame: Up to 10 weeks
measure: Terminal half-life (t½) of vadadustat
time frame: Up to 10 weeks
measure: Apparent total body clearance (CL/F) of vadadustat
time frame: Up to 10 weeks
measure: Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat
time frame: Baseline and end of study
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat-O-glucuronide
time frame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide
time frame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of vadadustat-O-glucuronide
time frame: Up to 10 weeks
measure: Reporting of treatment emergent adverse event (TEAE) as reported by study subjects
time frame: Up to 10 weeks
arm group label: Rabeprazole and Vadadustat
arm group type: Experimental
description: Subjects will receive vadadustat 300 mg on day 1, rabeprazole 20 mg every 12 hours on days 2 through 5 and vadadustat 300 mg and rabeprazole on day 6
intervention type: Drug
intervention name: Vadadustat
description: Vadadustat 300 mg
arm group label: Rabeprazole and Vadadustat
intervention type: Drug
intervention name: Rabeprazole
description: Oral Rabeprazole
arm group label: Rabeprazole and Vadadustat
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: Rabeprazole
sharing ipd: Undecided