<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/NCT02252835</url>
  </required_header>
  <id_info>
    <org_study_id>CB102-21426</org_study_id>
    <nct_id>NCT02252835</nct_id>
  </id_info>
  <brief_title>Evaluate the PK, PD, and Safety of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Patients With Gout</brief_title>
  <official_title>A Phase 2, Open-label, Drug-Drug Interaction Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination With Febuxostat for the Treatment of Hyperuricemia in Patients With Gout</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CymaBay Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CymaBay Therapeutics, Inc.</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate pharmacokinetics, pharmacodynamics, safety and&#xD;
      potential for drug-drug interaction of arhalofenate when combined with febuxostat in adult&#xD;
      population with gout.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients entering the six-week Treatment Period will receive once daily oral dosing of&#xD;
      arhalofenate during Weeks 1 and 2 (Days 1 through 14), combined once daily oral dosing of&#xD;
      arhalofenate and febuxostat during Weeks 3 and 4 (Days 15 through 28), and once daily oral&#xD;
      dosing of febuxostat during Weeks 5 and 6 (Days 29 through 42). In addition, all patients&#xD;
      will receive once daily oral dosing of colchicine throughout the Treatment Period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients achieving a target sUA &lt; 6.0, &lt; 5.0, &lt; 4.0, and &lt; 3.0 mg/dL on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-t) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination</measure>
    <time_frame>Days 14, 28, and 42</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(0-tau) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination</measure>
    <time_frame>Days 14, 28, and 42</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination</measure>
    <time_frame>Days 14, 28, and 42</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination</measure>
    <time_frame>Days 14, 28, and 42</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving a target sUA &lt; 6.0, &lt; 5.0, &lt; 4.0, and &lt; 3.0 mg/dL on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving a target sUA &lt; 6.0, &lt; 5.0, &lt; 4.0, and &lt; 3.0 mg/dL on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg</measure>
    <time_frame>Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg</measure>
    <time_frame>Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and percent reduction in sUA from baseline on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg</measure>
    <time_frame>Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving a target sUA &lt; 6.0, &lt; 5.0, &lt; 4.0, and &lt; 3.0 mg/dL after monotherapy treatment with arhalofenate 600 or 800 mg, or febuxostat 40 or 80 mg</measure>
    <time_frame>Day 15 or Day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline after monotherapy treatment with arhalofenate 600 or 800 mg, or febuxostat 40 or 80 mg</measure>
    <time_frame>Day 15 or Day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and percent reduction in sUA from baseline on Day 15 after monotherapy treatment with arhalofenate 600 or 800 mg</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and percent reduction in sUA from baseline on Day 43 after monotherapy treatment with febuxostat 40 or 80 mg</measure>
    <time_frame>Day 43</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kel and T1/2 of arhalofenate 800 mg and febuxostat 80 mg, if possible, when administered separately and in combination</measure>
    <time_frame>Days 14, 28, and 42</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>Days 1 through 43</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in physical examination findings</measure>
    <time_frame>Days 1 through 43</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in vital signs and safety laboratory tests</measure>
    <time_frame>Days 1 through 43</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Safety-related study drug discontinuations</measure>
    <time_frame>Days 1 through 43</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Deaths</measure>
    <time_frame>Days 1 through 43</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Gout</condition>
  <condition>Hyperuricemia</condition>
  <arm_group>
    <arm_group_label>Arhalofenate with febuxostat (PK cohort)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Arhalofenate with febuxostat (non-PK cohort)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Arhalofenate</intervention_name>
    <description>800 mg once daily orally for four weeks</description>
    <arm_group_label>Arhalofenate with febuxostat (PK cohort)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Febuxostat</intervention_name>
    <description>40 mg once daily orally for 1 week then up-titrated to 80 mg once daily orally for another three weeks</description>
    <arm_group_label>Arhalofenate with febuxostat (PK cohort)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Arhalofenate</intervention_name>
    <description>600 mg once daily orally for four weeks</description>
    <arm_group_label>Arhalofenate with febuxostat (non-PK cohort)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Febuxostat</intervention_name>
    <description>80 mg once daily orally for 1 week then down-titrated to 40 mg once daily orally for another three weeks</description>
    <arm_group_label>Arhalofenate with febuxostat (non-PK cohort)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colchicine</intervention_name>
    <description>0.6 mg daily</description>
    <arm_group_label>Arhalofenate with febuxostat (PK cohort)</arm_group_label>
    <arm_group_label>Arhalofenate with febuxostat (non-PK cohort)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patient, 18 to 75 years of age, inclusive&#xD;
&#xD;
          -  Known gout diagnosis (per criteria of the American Rheumatism Association)&#xD;
&#xD;
          -  Has an sUA ≥ 7.5 mg/dL&#xD;
&#xD;
          -  A female patient must be surgically sterile or post-menopausal (at least 45 years of&#xD;
             age with no history of menses for at least two years), or must agree to use two&#xD;
             medically accepted methods of contraception including a barrier method for the entire&#xD;
             duration of study participation unless she reports compete sexual abstinence. A female&#xD;
             patient must also not be pregnant or lactating&#xD;
&#xD;
          -  Estimated creatinine clearance (eCrCl) ≥ 60 ml/min, as calculated by Cockcroft-Gault&#xD;
             method&#xD;
&#xD;
          -  ALT or AST ≤ 3 times upper limit of normal (ULN) or total bilirubin ≤ 2 times ULN&#xD;
             (Gilbert's syndrome is permitted)&#xD;
&#xD;
          -  All other clinical laboratory parameters must be within normal limits or considered&#xD;
             not clinically significant&#xD;
&#xD;
          -  ECG must be normal, or if abnormal, considered not clinically significant&#xD;
&#xD;
          -  A patient who is taking a medication or agent (other than a ULT) known to influence&#xD;
             sUA levels must be on a stable dose and regimen of the medication for at least two&#xD;
             weeks prior to screening and must be willing to continue the same dose and regimen&#xD;
             during study participation&#xD;
&#xD;
          -  Expected to be able to tolerate a short course of oral NSAIDs and/or oral steroids as&#xD;
             may be needed to treat a gout flare&#xD;
&#xD;
          -  Must be able to swallow tablets&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with any ULT (e.g., allopurinol, febuxostat, probenecid, or benzbromarone)&#xD;
             within two weeks, or pegloticase within six months, prior to the sUA assessment at Day&#xD;
             1&#xD;
&#xD;
          -  Occurrence of a gout flare that has not resolved within one week prior to Day 1&#xD;
&#xD;
          -  Known or suspected secondary hyperuricemia (e.g., due to myeloproliferative disorder&#xD;
             or organ transplant)&#xD;
&#xD;
          -  Diagnosis of xanthinuria&#xD;
&#xD;
          -  Fractional excretion of urate &gt; 10%&#xD;
&#xD;
          -  History of documented or suspected kidney stones within five years prior to screening&#xD;
&#xD;
          -  Known infection with the human immunodeficiency virus (HIV) or history of hepatitis B&#xD;
             or C&#xD;
&#xD;
          -  Recent use/abuse of an illicit drug as determined by a positive urine drug screen&#xD;
&#xD;
          -  Uncontrolled hypertension that, in the opinion of the Investigator, would preclude&#xD;
             participation in the study&#xD;
&#xD;
          -  History of stroke, transient ischemic attack, acute myocardial infarction, congestive&#xD;
             heart failure (NYHA class II - IV), angina pectoris, coronary intervention procedure,&#xD;
             lower extremity bypass procedure, systemic or intracoronary fibrinolytic therapy&#xD;
             within 5 years of screening&#xD;
&#xD;
          -  History of cancer within five years of screening, with the following exceptions:&#xD;
             adequately treated non-melanoma skin cancer, non-metastatic prostate cancer, or in&#xD;
             situ cervical cancer&#xD;
&#xD;
          -  Body mass index (BMI) &gt; 42 kg/m2&#xD;
&#xD;
          -  Current or expected requirement for anticoagulant therapy, except for low dose (≤ 81&#xD;
             mg/day) aspirin, clopidogrel (Plavix) ≤ 75 mg/day, or prasugrel (Effient) ≤ 10 mg/day&#xD;
&#xD;
          -  Use of any of the following within eight weeks prior to screening: potent CYP3A4&#xD;
             inhibitors, cytotoxic agents (including azathioprine, mercaptopurine, cyclosporine,&#xD;
             cyclophosphamide, etc.), ranolazine, digoxin, theophylline, sulphonylureas,&#xD;
             thiazolidinediones (e.g., rosiglitazone or pioglitazone), desipramine, atypical&#xD;
             antipsychotic agents, loop diuretics, warfarin, or phenytoin&#xD;
&#xD;
          -  Chronic treatment with NSAIDs that cannot be safely discontinued-term use of NSAIDs is&#xD;
             permitted, e.g., when used to treat gout flares&#xD;
&#xD;
          -  Known hypersensitivity or intolerance to febuxostat or colchicine&#xD;
&#xD;
          -  Treatment with any other investigational therapy within 30 days or within five&#xD;
             half-lives, whichever is longer prior to Day 1&#xD;
&#xD;
          -  Any other condition that would compromise the safety of the patient, prevent&#xD;
             compliance with the study protocol, or compromise the quality of the clinical study,&#xD;
             as judged by the Investigator and/or Medical Monitor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra Steinberg, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>CymaBay Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vince &amp; Associates Clinical Research</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 20, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <disposition_first_submitted>February 16, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>March 9, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">March 30, 2015</disposition_first_posted>
  <last_update_submitted>March 30, 2015</last_update_submitted>
  <last_update_submitted_qc>March 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gout</mesh_term>
    <mesh_term>Hyperuricemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colchicine</mesh_term>
    <mesh_term>Febuxostat</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02252835
org study id: CB102-21426
nct id: NCT02252835
lead sponsor: 
The purpose of this study is to evaluate pharmacokinetics, pharmacodynamics, safety and
      potential for drug-drug interaction of arhalofenate when combined with febuxostat in adult
      population with gout.
Patients entering the six-week Treatment Period will receive once daily oral dosing of
      arhalofenate during Weeks 1 and 2 (Days 1 through 14), combined once daily oral dosing of
      arhalofenate and febuxostat during Weeks 3 and 4 (Days 15 through 28), and once daily oral
      dosing of febuxostat during Weeks 5 and 6 (Days 29 through 42). In addition, all patients
      will receive once daily oral dosing of colchicine throughout the Treatment Period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg
time frame: Day 29
measure: Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg
time frame: Day 29
measure: Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 800 mg and febuxostat 80 mg
time frame: Day 29
measure: AUC(0-t) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination
time frame: Days 14, 28, and 42
measure: AUC(0-tau) of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination
time frame: Days 14, 28, and 42
measure: Tmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination
time frame: Days 14, 28, and 42
measure: Cmax of arhalofenate 800 mg and febuxostat 80 mg when administered separately and in combination
time frame: Days 14, 28, and 42
measure: Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg
time frame: Day 29
measure: Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg
time frame: Day 29
measure: Absolute and percent reduction in sUA from baseline on Day 29 after treatment with arhalofenate 600 mg and febuxostat 40 mg
time frame: Day 29
measure: Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg
time frame: Day 22
measure: Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg
time frame: Day 22
measure: Absolute and percent reduction in sUA from baseline on Day 22 after treatment with arhalofenate 800 mg and febuxostat 40 mg, and with arhalofenate 600 mg and febuxostat 80 mg
time frame: Day 22
measure: Proportion of patients achieving a target sUA < 6.0, < 5.0, < 4.0, and < 3.0 mg/dL after monotherapy treatment with arhalofenate 600 or 800 mg, or febuxostat 40 or 80 mg
time frame: Day 15 or Day 43
measure: Proportion of patients achieving an sUA reduction of ≥ 2.0, ≥ 3.0, and ≥ 4.0 mg/dL from baseline after monotherapy treatment with arhalofenate 600 or 800 mg, or febuxostat 40 or 80 mg
time frame: Day 15 or Day 43
measure: Absolute and percent reduction in sUA from baseline on Day 15 after monotherapy treatment with arhalofenate 600 or 800 mg
time frame: Day 15
measure: Absolute and percent reduction in sUA from baseline on Day 43 after monotherapy treatment with febuxostat 40 or 80 mg
time frame: Day 43
measure: Kel and T1/2 of arhalofenate 800 mg and febuxostat 80 mg, if possible, when administered separately and in combination
time frame: Days 14, 28, and 42
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
time frame: Days 1 through 43
measure: Change in physical examination findings
time frame: Days 1 through 43
measure: Change in vital signs and safety laboratory tests
time frame: Days 1 through 43
measure: Safety-related study drug discontinuations
time frame: Days 1 through 43
measure: Deaths
time frame: Days 1 through 43
arm group label: Arhalofenate with febuxostat (PK cohort)
arm group type: Experimental
arm group label: Arhalofenate with febuxostat (non-PK cohort)
arm group type: Experimental
intervention type: Drug
intervention name: Arhalofenate
description: 800 mg once daily orally for four weeks
arm group label: Arhalofenate with febuxostat (PK cohort)
intervention type: Drug
intervention name: Febuxostat
description: 40 mg once daily orally for 1 week then up-titrated to 80 mg once daily orally for another three weeks
arm group label: Arhalofenate with febuxostat (PK cohort)
intervention type: Drug
intervention name: Arhalofenate
description: 600 mg once daily orally for four weeks
arm group label: Arhalofenate with febuxostat (non-PK cohort)
intervention type: Drug
intervention name: Febuxostat
description: 80 mg once daily orally for 1 week then down-titrated to 40 mg once daily orally for another three weeks
arm group label: Arhalofenate with febuxostat (non-PK cohort)
intervention type: Drug
intervention name: Colchicine
description: 0.6 mg daily
arm group label: Arhalofenate with febuxostat (PK cohort)
arm group label: Arhalofenate with febuxostat (non-PK cohort)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Alexandra Steinberg, MD, PhD
role: Study Director
affiliation: CymaBay Therapeutics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Gout
mesh term: Hyperuricemia
mesh term: Colchicine
mesh term: Febuxostat