<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/NCT01689116</url>
  </required_header>
  <id_info>
    <org_study_id>402-C-1006</org_study_id>
    <nct_id>NCT01689116</nct_id>
  </id_info>
  <brief_title>Multiple-Dose Study of Effect of Bardoxolone Methyl on QT/QTC Interval Volunteers</brief_title>
  <official_title>A Blinded Randomized Parallel Trial to Define the ECG Effects of Bardoxolone Methyl Using a Clinical and a Supratherapeutic Dose Compared to Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: A Thorough ECG Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Reata Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Reata Pharmaceuticals, Inc.</source>
  <brief_summary>
    <textblock>
      This is a single-center, multiple-dose, randomized, double-blind, double-dummy,&#xD;
      placebo-controlled, active-comparator, parallel study in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in QT/QTc interval</measure>
    <time_frame>Baseline, Day 6 and Day 13</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration</measure>
    <time_frame>Day 1 and Day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed concentration</measure>
    <time_frame>Day 1 and Day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from time 0 to last observed concentration</measure>
    <time_frame>Day 1 and Day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under curve for the dosing interval</measure>
    <time_frame>Day 1 and Day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation index for maximum observed concentration</measure>
    <time_frame>Day 1 and day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation index for area under the curve from time 0 to 24 hours</measure>
    <time_frame>Day 1 and Day 6</time_frame>
    <description>0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>Approximately 6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">179</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Bardoxolone Methyl 20mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Bardoxolone Methyl 80mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Bardoxolone Methyl Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxifloxacin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bardoxolone Methyl 20mg</intervention_name>
    <description>Oral</description>
    <arm_group_label>Bardoxolone Methyl 20mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bardoxolone Methyl 80mg</intervention_name>
    <description>Oral</description>
    <arm_group_label>Bardoxolone Methyl 80mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bardoxolone Methyl Placebo</intervention_name>
    <description>Oral</description>
    <arm_group_label>Bardoxolone Methyl 20mg</arm_group_label>
    <arm_group_label>Bardoxolone Methyl Placebo</arm_group_label>
    <arm_group_label>Moxifloxacin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin 400mg</intervention_name>
    <description>Oral</description>
    <arm_group_label>Moxifloxacin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin Placebo</intervention_name>
    <description>Oral</description>
    <arm_group_label>Bardoxolone Methyl 20mg</arm_group_label>
    <arm_group_label>Bardoxolone Methyl 80mg</arm_group_label>
    <arm_group_label>Bardoxolone Methyl Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All subjects must meet all of the following criteria to be included in the study:&#xD;
&#xD;
          1. Healthy male and female subjects between 18 to 50 years of age, inclusive. Healthy as&#xD;
             determined by medical history, physical examination, electrocardiogram (ECG), and&#xD;
             clinical laboratory measurements performed at screening;&#xD;
&#xD;
          2. BMI greater than or equal to 18 kg/m2 but not to exceed 32 kg/m2;&#xD;
&#xD;
          3. 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 in section&#xD;
             12.8.3 or abstain from sexual activity for the duration of the study and for at least&#xD;
             3 weeks after discontinuation of study drug;&#xD;
&#xD;
          4. Male subjects and their partners of childbearing potential must use two methods of&#xD;
             contraception, one of which must be a barrier method, for the duration of the study&#xD;
             and for 30 days after completion;&#xD;
&#xD;
          5. Agree to abstain from alcohol consumption up to 3 days before dosing and throughout&#xD;
             duration of the study (including the Study Day 13 visit);&#xD;
&#xD;
          6. Agree to abstain from strenuous exercise from 3 days before dosing and throughout&#xD;
             duration of the study (including the Study Day 13 visit);&#xD;
&#xD;
          7. Able to effectively communicate with the investigator and other testing center&#xD;
             personnel;&#xD;
&#xD;
          8. Able to participate, and willing to give written informed consent and to comply with&#xD;
             the study restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All subjects with any of the following conditions or characteristics must be excluded from&#xD;
        the study:&#xD;
&#xD;
          1. Currently participating in another study of an investigational drug (or a medical&#xD;
             device) or have participated in another clinical study of an investigational drug (or&#xD;
             a medical device) within 30 days of Study Day -1, 5 half-lives or twice the duration&#xD;
             of biological effect of the previous investigational drug (whichever is longer);&#xD;
&#xD;
          2. Known hypersensitivity to any component in the formulation of the study drug,&#xD;
             bardoxolone methyl;&#xD;
&#xD;
          3. Any medical or dental procedure, no matter how minor, that is planned or anticipated&#xD;
             to occur during the conduct of the study;&#xD;
&#xD;
          4. History of drug or alcohol abuse or dependence within the last year;&#xD;
&#xD;
          5. History of smoking or tobacco use within the 6 months prior to Study Day -1;&#xD;
&#xD;
          6. Donation or receipt of blood or blood components within the 4 weeks prior to Study Day&#xD;
             -1. The investigator should instruct subjects who participate in this study not to&#xD;
             donate blood or blood components for 4 weeks after the completion of the study;&#xD;
&#xD;
          7. History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or&#xD;
             Torsades de Pointes, structural heart disease, or family history of long QT syndrome&#xD;
             (suggested by sudden death due to cardiac causes at a young age of a close relative);&#xD;
&#xD;
          8. Evidence of any of the following cardiac conduction abnormalities based on the safety&#xD;
             ECG at Screening:&#xD;
&#xD;
               -  Fridericia's correction for QT (QTcF) interval &gt; 450 ms for males, &gt; 470 ms for&#xD;
                  females;&#xD;
&#xD;
               -  PR interval &lt; 110 ms or &gt; 240 ms;&#xD;
&#xD;
               -  Intraventricular conduction delay with QRS duration &gt;120 ms;&#xD;
&#xD;
               -  Resting heart rate &lt; 40 bpm or &gt; 90 bpm;&#xD;
&#xD;
               -  Pathological Q-waves (defined as Q-wave &gt; 40 ms or depth &gt; 0.4-0.5 mV);&#xD;
&#xD;
               -  Second- or third-degree atrioventricular block (AVB);&#xD;
&#xD;
               -  Electrocardiographic evidence of complete left bundle branch block (LBBB), right&#xD;
                  bundle branch block (RBBB), or incomplete left bundle branch block (LBBB);&#xD;
&#xD;
               -  Ventricular pre-excitation;&#xD;
&#xD;
               -  Atrial fibrillation, atrial flutter, or artificial cardiac pacemaker;&#xD;
&#xD;
          9. Screening ECG renders measurement of QT interval in lead II imprecise (for example:&#xD;
             flat T waves, arrhythmias);&#xD;
&#xD;
         10. Subjects who have a screening supine blood pressure (BP) outside 90-145 mm Hg systolic&#xD;
             or 45-95 mm Hg diastolic (measured following at least a 10-minute rest). Blood&#xD;
             pressure may be re-tested twice in the supine position at intervals of 5 minutes. The&#xD;
             pressure elevation is considered sustained if either the systolic or the diastolic&#xD;
             pressure exceeds the stated limits after three assessments and the subject may not be&#xD;
             randomized;&#xD;
&#xD;
         11. Use of any concomitant medications that are known to prolong QT/QTc interval within 30&#xD;
             days prior to Study Day -1;&#xD;
&#xD;
         12. Allergy to moxifloxacin or any fluoroquinolone antibiotic;&#xD;
&#xD;
         13. A positive test for drug(s) of abuse (alcohol, amphetamines, benzodiazepines,&#xD;
             barbiturates, cocaine, opiates, or cannabinoids) at the screening or the Day -2 visit;&#xD;
&#xD;
         14. Any concurrent clinical conditions that in the judgment of the investigator could&#xD;
             either potentially pose a health risk to the subject while involved in the study or&#xD;
             could potentially influence the study outcome;&#xD;
&#xD;
         15. Positive test results for human immunodeficiency virus type 1 or 2 antibody at&#xD;
             screening;&#xD;
&#xD;
         16. Any condition possibly affecting absorption, distribution, metabolism or excretion of&#xD;
             drugs that may confound the analyses conducted in this study (for example: previous&#xD;
             surgery on the gastrointestinal tract that includes removal of parts of stomach,&#xD;
             bowel, liver, gall bladder, pancreas, venocaval shunts, or transjugular intrahepatic&#xD;
             portosystemic shunts]);&#xD;
&#xD;
         17. Evidence or history of or concurrent clinically significant allergic (except for&#xD;
             untreated, asymptomatic, seasonal allergies at time of dose administration),&#xD;
             hematological, endocrine, immunological, renal, pulmonary, gastrointestinal,&#xD;
             cardiovascular, hepatic, psychiatric, or neurological disease that in the judgment of&#xD;
             the investigator could potentially either pose a health risk to the subject during the&#xD;
             study or influence the study outcome;&#xD;
&#xD;
         18. Evidence of hepatic or biliary dysfunction including elevation of total bilirubin,&#xD;
             direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT),&#xD;
             gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), or alkaline phosphatase&#xD;
             levels to greater than the upper limit of normal (ULN) at screening;&#xD;
&#xD;
         19. Abnormal hematological and biochemical parameters, including neutrophil count &lt; 1500&#xD;
             cells/mm3, Hgb &lt; 11 g/dL in females or &lt; 12 g/dL in males, platelet count &lt; 90,000&#xD;
             cells/mm3, creatinine ≥ 1.5 X ULN, albumin ≤ 3 g/dL, serum amylase or lipase ≥ 1.5X&#xD;
             ULN at screening;&#xD;
&#xD;
         20. Positive test results for hepatitis B virus antibody, or hepatitis C virus antibody at&#xD;
             screening;&#xD;
&#xD;
         21. Use of or need for any prescription or non-prescription systemic drug(s) including&#xD;
             vitamins or herbal preparations other than drugs used for contraception, aspirin,&#xD;
             acetaminophen, or other non-steroidal anti-inflammatory agents, within 10 days before&#xD;
             Study Day -1 or during the study;&#xD;
&#xD;
         22. Use of aspirin, non-steroidal anti-inflammatory agents, or acetaminophen within 5 days&#xD;
             prior to Study Day -1;&#xD;
&#xD;
         23. Consumption of alcohol- or caffeine-containing compounds within 24 hours before Day -2&#xD;
             visit;&#xD;
&#xD;
         24. Consumption of citrus juice within the 7 days before Day -2 visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Spaulding Clinical Research, LLC</name>
      <address>
        <city>West Bend</city>
        <state>Wisconsin</state>
        <zip>53012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>April 9, 2013</last_update_submitted>
  <last_update_submitted_qc>April 9, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 11, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Norgestimate, ethinyl estradiol drug combination</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/NCT01689116
org study id: 402-C-1006
nct id: NCT01689116
lead sponsor: 
This is a single-center, multiple-dose, randomized, double-blind, double-dummy,
      placebo-controlled, active-comparator, parallel study in healthy volunteers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in QT/QTc interval
time frame: Baseline, Day 6 and Day 13
measure: Maximum observed concentration
time frame: Day 1 and Day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Time to maximum observed concentration
time frame: Day 1 and Day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Area under the plasma concentration-time curve from time 0 to last observed concentration
time frame: Day 1 and Day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Area under curve for the dosing interval
time frame: Day 1 and Day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Accumulation index for maximum observed concentration
time frame: Day 1 and day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Accumulation index for area under the curve from time 0 to 24 hours
time frame: Day 1 and Day 6
description: 0 (immediately before dose administrations), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours following dose
measure: Number of Adverse Events
time frame: Approximately 6 months
arm group label: Bardoxolone Methyl 20mg
arm group type: Experimental
arm group label: Bardoxolone Methyl 80mg
arm group type: Experimental
arm group label: Bardoxolone Methyl Placebo
arm group type: Placebo Comparator
arm group label: Moxifloxacin
arm group type: Active Comparator
intervention type: Drug
intervention name: Bardoxolone Methyl 20mg
description: Oral
arm group label: Bardoxolone Methyl 20mg
intervention type: Drug
intervention name: Bardoxolone Methyl 80mg
description: Oral
arm group label: Bardoxolone Methyl 80mg
intervention type: Drug
intervention name: Bardoxolone Methyl Placebo
description: Oral
arm group label: Bardoxolone Methyl 20mg
arm group label: Bardoxolone Methyl Placebo
arm group label: Moxifloxacin
intervention type: Drug
intervention name: Moxifloxacin 400mg
description: Oral
arm group label: Moxifloxacin
intervention type: Drug
intervention name: Moxifloxacin Placebo
description: Oral
arm group label: Bardoxolone Methyl 20mg
arm group label: Bardoxolone Methyl 80mg
arm group label: Bardoxolone Methyl Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: Norgestimate, ethinyl estradiol drug combination