<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/NCT03272425</url>
  </required_header>
  <id_info>
    <org_study_id>RDEA594-504</org_study_id>
    <nct_id>NCT03272425</nct_id>
  </id_info>
  <brief_title>Lesinurad/Allopurinol 200/300 Fixed-Dose Combination (FDC) Tablets Bioequivalence.</brief_title>
  <official_title>A Randomized, Open-label, Replicate, Crossover, 4-period Study to Assess the Bioequivalence of Lesinurad/Allopurinol Fixed-dose Combination 200/300 mg Tablets From Ardea Biosciences, Inc. (Test Drug) Versus Lesinurad, 200 mg Tablet From AstraZeneca (Comparator 1) Coadministered With Zyloric®, Allopurinol 300 mg Tablet From Aspen Pharma Industria Farmaceutica Ltda. (Comparator 2) in Healthy Female and Male Adult Subjects, Under Fasting Conditions.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ardea Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ardea Biosciences, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the bioequivalence between lesinurad/allopurinol 200/300 FDC tablets and&#xD;
      coadministered lesinurad and allopurinol tablets in the fasted state based on the&#xD;
      pharmacokinetic (PK) evaluation of lesinurad and allopurinol in healthy adult subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">October 4, 2017</completion_date>
  <primary_completion_date type="Actual">October 4, 2017</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets</measure>
    <time_frame>Days 1, 8, 15 and 22</time_frame>
    <description>Cmax is the maximum observed concentration of a drug after administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK endpoints in terms of area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint (AUC last) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets</measure>
    <time_frame>Days 1, 8, 15 and 22</time_frame>
    <description>AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK endpoints in terms of area under the plasma concentration time curve from and from zero to infinity (AUC 0-∞) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets</measure>
    <time_frame>Days 1, 8, 15 and 22</time_frame>
    <description>AUC 0-∞ is a meausre of total concentration from time zero to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK endpoints in terms of time of occurrence of maximum observed concentration (tmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets</measure>
    <time_frame>Days 1, 8, 15 and 22</time_frame>
    <description>Tmax is the time of occurrence of cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets</measure>
    <time_frame>Days 1, 8, 15 and 22</time_frame>
    <description>t1/2 is a measure of apparent terminal half-life</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events in terms of changes in laboratory parameters</measure>
    <time_frame>26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events in terms of electrocardiogram parameters</measure>
    <time_frame>26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events in terms of vital signs</measure>
    <time_frame>26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events in terms of physical examination findings</measure>
    <time_frame>26 days</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Gout</condition>
  <arm_group>
    <arm_group_label>Sequence ABBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence BABA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence ABAB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence BAAB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lesinurad/allopurinol 200/300 FDC tablets</intervention_name>
    <description>Test Drug</description>
    <arm_group_label>Sequence ABAB</arm_group_label>
    <arm_group_label>Sequence ABBA</arm_group_label>
    <arm_group_label>Sequence BAAB</arm_group_label>
    <arm_group_label>Sequence BABA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lesinurad 200 mg</intervention_name>
    <description>Comparator 1</description>
    <arm_group_label>Sequence ABAB</arm_group_label>
    <arm_group_label>Sequence ABBA</arm_group_label>
    <arm_group_label>Sequence BAAB</arm_group_label>
    <arm_group_label>Sequence BABA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>allopurinol 300 mg</intervention_name>
    <description>Comparator 2</description>
    <arm_group_label>Sequence ABAB</arm_group_label>
    <arm_group_label>Sequence ABBA</arm_group_label>
    <arm_group_label>Sequence BAAB</arm_group_label>
    <arm_group_label>Sequence BABA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index ranging between 18.5 kg/m2 and 30 kg/m2.&#xD;
&#xD;
          -  Screening serum urate level is ≤ 7.0 mg/dL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Asian subject who has a positive test for the HLA-B*5801 allele.&#xD;
&#xD;
          -  History or current diagnosis of kidney stones.&#xD;
&#xD;
          -  Estimated creatinine clearance, as determined at Screening, of ≤ 80 mL/min calculated&#xD;
             by the Cockcroft-Gault formula using ideal body weight.&#xD;
&#xD;
          -  Undergone major surgery within 3 months prior to Screening.&#xD;
&#xD;
          -  Donated blood within 4 weeks prior to Day 1 or experienced an event (other than blood&#xD;
             donation) of significant blood loss (&gt; 450 mL) within 12 weeks prior to Day 1 or has&#xD;
             given a plasma donation within 4 weeks prior to Day 1.&#xD;
&#xD;
          -  Inadequate venous access or unsuitable veins for repeated venipuncture.&#xD;
&#xD;
          -  Received any strong or moderate enzyme-inducing drug or product within 2 months prior&#xD;
             to Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>N. Bhakta</last_name>
    <role>Study Director</role>
    <affiliation>Ardea Biosciences, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CAEP - Centro Avançado de Estudos e Pesquisas Ltda.</name>
      <address>
        <city>Campinas</city>
        <state>Sao Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>November 6, 2018</last_update_submitted>
  <last_update_submitted_qc>November 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2018</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>Allopurinol</mesh_term>
    <mesh_term>Lesinurad</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03272425
org study id: RDEA594-504
nct id: NCT03272425
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To assess the bioequivalence between lesinurad/allopurinol 200/300 FDC tablets and
      coadministered lesinurad and allopurinol tablets in the fasted state based on the
      pharmacokinetic (PK) evaluation of lesinurad and allopurinol in healthy adult subjects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
time frame: Days 1, 8, 15 and 22
description: Cmax is the maximum observed concentration of a drug after administration
measure: PK endpoints in terms of area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint (AUC last) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
time frame: Days 1, 8, 15 and 22
description: AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint
measure: PK endpoints in terms of area under the plasma concentration time curve from and from zero to infinity (AUC 0-∞) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
time frame: Days 1, 8, 15 and 22
description: AUC 0-∞ is a meausre of total concentration from time zero to infinity
measure: PK endpoints in terms of time of occurrence of maximum observed concentration (tmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
time frame: Days 1, 8, 15 and 22
description: Tmax is the time of occurrence of cmax
measure: PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
time frame: Days 1, 8, 15 and 22
description: t1/2 is a measure of apparent terminal half-life
measure: Incidence of Adverse Events in terms of changes in laboratory parameters
time frame: 26 days
measure: Incidence of Adverse Events in terms of electrocardiogram parameters
time frame: 26 days
measure: Incidence of Adverse Events in terms of vital signs
time frame: 26 days
measure: Incidence of Adverse Events in terms of physical examination findings
time frame: 26 days
arm group label: Sequence ABBA
arm group type: Experimental
description: Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
arm group label: Sequence BABA
arm group type: Experimental
description: Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
arm group label: Sequence ABAB
arm group type: Experimental
description: Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
arm group label: Sequence BAAB
arm group type: Experimental
description: Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
intervention type: Drug
intervention name: lesinurad/allopurinol 200/300 FDC tablets
description: Test Drug
arm group label: Sequence ABAB
arm group label: Sequence ABBA
arm group label: Sequence BAAB
arm group label: Sequence BABA
intervention type: Drug
intervention name: lesinurad 200 mg
description: Comparator 1
arm group label: Sequence ABAB
arm group label: Sequence ABBA
arm group label: Sequence BAAB
arm group label: Sequence BABA
intervention type: Drug
intervention name: allopurinol 300 mg
description: Comparator 2
arm group label: Sequence ABAB
arm group label: Sequence ABBA
arm group label: Sequence BAAB
arm group label: Sequence BABA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: N. Bhakta
role: Study Director
affiliation: Ardea Biosciences, Inc.
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Allopurinol
mesh term: Lesinurad
sharing ipd: No