<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/NCT03264079</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-1701</org_study_id>
    <nct_id>NCT03264079</nct_id>
  </id_info>
  <brief_title>Effect of Itraconazole on the Pharmacokinetics of Bardoxolone Methyl in Healthy Adults</brief_title>
  <official_title>An Open-Label Study of the Effect of a Strong CYP3A4 Inhibitor (Itraconazole) on the Pharmacokinetics of Bardoxolone Methyl in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Reata Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Reata Pharmaceuticals, Inc.</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 trial will study the impact of a strong CYP3A4 inhibitor (itraconazole) on the&#xD;
      pharmacokinetics of bardoxolone methyl (RTA 402) in healthy adult subjects.&#xD;
&#xD;
      This is an open-label, fixed-sequence crossover pharmacokinetic (PK) study in healthy&#xD;
      volunteers.&#xD;
&#xD;
      Subjects will complete a screening visit within 28 days of Study Day 1. Subjects must qualify&#xD;
      for the study based on inclusion/exclusion criteria. For Period 1, all qualified subjects&#xD;
      shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1. For Period 2,&#xD;
      following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be&#xD;
      administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone&#xD;
      methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration).&#xD;
&#xD;
      Bardoxolone methyl doses will be administered under fasted conditions. Itraconazole will be&#xD;
      administered under fed conditions on Study Days 15-17, and Study Days 19-27.&#xD;
&#xD;
      On study Day 18, itraconazole will be administered under fasted conditions. Subjects will be&#xD;
      confined beginning on Study Day -1 through the last blood sample collection on Study Day 9&#xD;
      during Period 1, and from Study Day 14 through the last PK blood draw on Study Day 28 during&#xD;
      Period 2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2017</start_date>
  <completion_date type="Actual">November 13, 2017</completion_date>
  <primary_completion_date type="Actual">November 13, 2017</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>All participants are placed into a one group to receive two interventions: one intervention during Period 1 and a second intervention during Period 2.&#xD;
For Period 1, all qualified subjects shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1.&#xD;
For Period 2, following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve of bardoxolone methyl from time 0 to the last measurable time point (AUC0-t).</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve of bardoxolone methyl extrapolated to infinity (AUC0-inf)</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed drug concentration (Cmax) in plasma of bardoxolone methyl</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Bardoxolone methyl 10 mg and Itraconazole 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Period 1: Bardoxolone methyl capsules 10 mg Period 2: two Itraconazole capsules 100 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bardoxolone methyl capsules 10 mg</intervention_name>
    <description>One 10 mg capsule of bardoxolone methyl administered on Study Day 1 (Period 1) of the trial and one 10 mg capsule of bardoxolone methyl administered on Study Day 18 (Period 2) of the trial</description>
    <arm_group_label>Bardoxolone methyl 10 mg and Itraconazole 200 mg</arm_group_label>
    <other_name>RTA 402</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole capsules 100 mg</intervention_name>
    <description>Two 100 mg capsules of itraconazole administered once daily during Study Days 15 - 27 (Period 2) of the trial</description>
    <arm_group_label>Bardoxolone methyl 10 mg and Itraconazole 200 mg</arm_group_label>
    <other_name>Sporanox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female and age is between 18 and 55 years, inclusive;&#xD;
&#xD;
          -  Female subjects of childbearing potential must not be planning a pregnancy, pregnant,&#xD;
             or lactating, and must have a negative serum pregnancy test result before enrollment&#xD;
             into the study, and must be willing to use contraception as specified or abstain from&#xD;
             sexual activity for the duration of the study;&#xD;
&#xD;
          -  If male, subject must be surgically sterile or practicing an approved method of&#xD;
             contraception, from initial study drug administration through 90 days after&#xD;
             administration of the last dose of study drug;&#xD;
&#xD;
          -  If male, subject agrees to abstain from sperm donation through 90 days after&#xD;
             administration of the last dose of study drug;&#xD;
&#xD;
          -  Body Mass Index (BMI) is ≥ 18 to ≤31 kg/m2, inclusive;&#xD;
&#xD;
          -  A condition of general good health, based upon the results of a medical history,&#xD;
             physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram&#xD;
             (ECG), as judged by the investigator;&#xD;
&#xD;
          -  Must voluntarily sign and date each informed consent, approved by an Institutional&#xD;
             Review Board (IRB), prior to the initiation of any screening or study-specific&#xD;
             procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of clinically significant drug allergies, including allergies to any of the&#xD;
             components of the investigational product and/or clinically significant food allergies&#xD;
             as determined by the investigator;&#xD;
&#xD;
          -  Presence or history of any significant cardiovascular, gastrointestinal, hepatic,&#xD;
             renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic, or&#xD;
             psychiatric disease, as determined by the investigator;&#xD;
&#xD;
          -  Presence of any other condition (including surgery) known to interfere with the&#xD;
             absorption, distribution, metabolism, or excretion of medicines;&#xD;
&#xD;
          -  Known hypersensitivity to any component in the formulations of bardoxolone methyl, or&#xD;
             SPORANOX®;&#xD;
&#xD;
          -  Requirement for any over-the-counter and/or prescription medication, vitamins, and/or&#xD;
             herbal supplements on a regular basis;&#xD;
&#xD;
          -  Use of any medications (over-the-counter and/or prescription medication), vitamins,&#xD;
             and/or herbal supplements, within the 30-day period prior to study drug administration&#xD;
             or within 5 half-lives (if known), whichever is longer;&#xD;
&#xD;
          -  Recent (6-month) history of drug or alcohol abuse;&#xD;
&#xD;
          -  B-type natriuretic peptide (BNP) level &gt;200 pg/mL at screening;&#xD;
&#xD;
          -  Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
             antibody (HCV Ab), or HIV antibodies (HIV Ab) at screening;&#xD;
&#xD;
          -  Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt&#xD;
             of a transfusion of any blood product within 8 weeks prior to study drug&#xD;
             administration;&#xD;
&#xD;
          -  Receipt of any investigational product within a time period equal to 10 half-lives of&#xD;
             the product, if known, or a minimum of 30 days prior to study drug administration;&#xD;
&#xD;
          -  Positive screen results for drugs of abuse, alcohol, or cotinine at screening or Day&#xD;
             -1;&#xD;
&#xD;
          -  Consumption of alcohol within 72 hours prior to study drug administration;&#xD;
&#xD;
          -  Consumption of grapefruit, grapefruit products, star fruit, star fruit products, or&#xD;
             Seville oranges within the 72-hour period prior to study drug administration;&#xD;
&#xD;
          -  Use of tobacco or nicotine-containing products within the 6-month period preceding&#xD;
             study drug administration;&#xD;
&#xD;
          -  Current enrollment in another clinical study;&#xD;
&#xD;
          -  Screening laboratory analyses that show any of the following abnormal laboratory&#xD;
             results:&#xD;
&#xD;
               1. Alanine transaminase (ALT) or aspartate aminotransferase (AST) levels above the&#xD;
                  upper limit of normal (ULN);&#xD;
&#xD;
               2. Clinically significant abnormal ECG; ECG with QTc using Fridericia's correction&#xD;
                  formula (QTcF) &gt; 450 msec is exclusionary;&#xD;
&#xD;
               3. Consideration by the investigator, for any reason, that the subject is an&#xD;
                  unsuitable candidate to receive either bardoxolone methyl or itraconazole.&#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>
  <location>
    <facility>
      <name>Medpace Clinical Pharmacology Unit</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>November 27, 2017</last_update_submitted>
  <last_update_submitted_qc>November 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RTA 402</keyword>
  <keyword>Bardoxolone methyl</keyword>
  <keyword>Itraconazole</keyword>
  <keyword>Sporanox</keyword>
  <keyword>CYP3A4</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03264079
org study id: 402-C-1701
nct id: NCT03264079
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This trial will study the impact of a strong CYP3A4 inhibitor (itraconazole) on the
      pharmacokinetics of bardoxolone methyl (RTA 402) in healthy adult subjects.

      This is an open-label, fixed-sequence crossover pharmacokinetic (PK) study in healthy
      volunteers.

      Subjects will complete a screening visit within 28 days of Study Day 1. Subjects must qualify
      for the study based on inclusion/exclusion criteria. For Period 1, all qualified subjects
      shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1. For Period 2,
      following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be
      administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone
      methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration).

      Bardoxolone methyl doses will be administered under fasted conditions. Itraconazole will be
      administered under fed conditions on Study Days 15-17, and Study Days 19-27.

      On study Day 18, itraconazole will be administered under fasted conditions. Subjects will be
      confined beginning on Study Day -1 through the last blood sample collection on Study Day 9
      during Period 1, and from Study Day 14 through the last PK blood draw on Study Day 28 during
      Period 2.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All participants are placed into a one group to receive two interventions: one intervention during Period 1 and a second intervention during Period 2.
For Period 1, all qualified subjects shall receive a single oral dose of bardoxolone methyl (10 mg) on Day 1.
For Period 2, following a washout of 14 days, itraconazole (SPORANOX®) capsules (100 mg) will be administered as a 200-mg single daily dose on Study Days 15 through 27, with bardoxolone methyl (10 mg) administered on Day 18 (1 hour after itraconazole administration)
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the plasma concentration-time curve of bardoxolone methyl from time 0 to the last measurable time point (AUC0-t).
time frame: 28 days
measure: Area under the plasma concentration-time curve of bardoxolone methyl extrapolated to infinity (AUC0-inf)
time frame: 28 days
measure: Maximum observed drug concentration (Cmax) in plasma of bardoxolone methyl
time frame: 28 days
arm group label: Bardoxolone methyl 10 mg and Itraconazole 200 mg
arm group type: Experimental
description: Period 1: Bardoxolone methyl capsules 10 mg Period 2: two Itraconazole capsules 100 mg
intervention type: Drug
intervention name: Bardoxolone methyl capsules 10 mg
description: One 10 mg capsule of bardoxolone methyl administered on Study Day 1 (Period 1) of the trial and one 10 mg capsule of bardoxolone methyl administered on Study Day 18 (Period 2) of the trial
arm group label: Bardoxolone methyl 10 mg and Itraconazole 200 mg
other name: RTA 402
intervention type: Drug
intervention name: Itraconazole capsules 100 mg
description: Two 100 mg capsules of itraconazole administered once daily during Study Days 15 - 27 (Period 2) of the trial
arm group label: Bardoxolone methyl 10 mg and Itraconazole 200 mg
other name: Sporanox
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Itraconazole