<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/NCT02256033</url>
  </required_header>
  <id_info>
    <org_study_id>6002-016</org_study_id>
    <nct_id>NCT02256033</nct_id>
  </id_info>
  <brief_title>Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline</brief_title>
  <official_title>Effect of Mild Hepatic Impairment (Child-Pugh Class A) on the Single-dose Pharmacokinetics of Istradefylline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kyowa Hakko Kirin Pharma, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kyowa Kirin, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether mild liver impairment affects blood levels of&#xD;
      istradefylline in humans. Decreased liver function could possibly increase istradefylline&#xD;
      levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, parallel group, single-dose study to determine the&#xD;
      single-dose PK of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh&#xD;
      Class A) and in subjects with normal hepatic function. Ten subjects with mild HI (Child-Pugh&#xD;
      Class A) and 10 subjects with normal hepatic function (matched for age, gender, race, and&#xD;
      BMI) will be enrolled. Enrollment of the subjects with normal hepatic function will be&#xD;
      subsequent to the HI subjects.&#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 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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of pharmacokinetic parameter istradefylline (Area under the concentration-time curve [AUC]) between subjects with hepatic impairment and healthy subjects with normal hepatic function using an analysis of variance model</measure>
    <time_frame>Intermittently for a total of 36 days</time_frame>
    <description>Single-dose pharmacokinetics (PK) of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh Class A) and in subjects with normal hepatic function</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events and serious adverse events</measure>
    <time_frame>Continuously for 36 days</time_frame>
    <description>Safety and tolerability will be assessed through review of recorded adverse events and serious adverse events.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Istradefylline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One 40-mg tablet of istradefylline administered on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Istradefylline</intervention_name>
    <description>One 40 mg-tablet administered on Day 1</description>
    <arm_group_label>Istradefylline</arm_group_label>
    <other_name>KW-6002</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All subjects:&#xD;
&#xD;
          -  Non-smoking males and females 18-75 years of age, inclusive;&#xD;
&#xD;
          -  Men and women with procreative potential must practice medically reliable double&#xD;
             barrier methods of birth control;&#xD;
&#xD;
          -  Body mass index (BMI): 18.0-35.0 kg/m2, inclusive:&#xD;
&#xD;
          -  Must abstain from drugs and nutrients known as moderate to potent inhibitors/inducers&#xD;
             of CYP3A4 and CYP1A enzymes. These agents should be discontinued at least 4 weeks&#xD;
             before the istradefylline dose (Day 1) until the Follow-up visit.&#xD;
&#xD;
          -  Negative results at Screening and Baseline for the following screening laboratory&#xD;
             tests: urine drug screen (amphetamines, barbiturates, benzodiazepines, opiates,&#xD;
             cannabinoids, and cocaine). Documented prescription use in subjects with mild HI for&#xD;
             medications included in the urine drug of abuse test is permitted as long as the dose&#xD;
             is stable for at least 2 weeks;&#xD;
&#xD;
        Subjects with Normal Hepatic Function only&#xD;
&#xD;
          -  Medical history without clinically significant or ongoing pathology, which in the&#xD;
             opinion of the Investigator will preclude the subject's participation in, or influence&#xD;
             the outcome of the study;&#xD;
&#xD;
        Subjects with Mild Hepatic Impairment only&#xD;
&#xD;
          -  Stable, mild liver disease (Child-Pugh A [5 to 6 points]); of cryptogenic,&#xD;
             post-hepatic, hepatitis B/C virus, or alcoholic origin;&#xD;
&#xD;
          -  Stable hepatic impairment, defined as no clinically significant change in disease&#xD;
             status within the last 30 days, as documented by the subject's recent medical history;&#xD;
&#xD;
        Additional inclusion criteria apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are taking oral contraceptives or long-term injectable or&#xD;
             implantable hormonal contraceptives, pregnant, lactating, or breast-feeding;&#xD;
&#xD;
          -  Known history of treatment for drug or alcohol addiction within the previous 12 months&#xD;
             or &gt; 14 untis of alcohol consumption per week, or alcohol consumption within 1 week&#xD;
             prior to dosing;&#xD;
&#xD;
          -  Positive test results for human immunodeficiency virus (HIV), or Hepatitis B surface&#xD;
             antigen;&#xD;
&#xD;
          -  Difficulty fasting or eating the standard meals that will be provided;&#xD;
&#xD;
          -  Use of tobacco or nicotine-containing products within 90 days of the study start to&#xD;
             the Follow-up visit (to be confirmed by urine cotinine test);&#xD;
&#xD;
        Subjects with Hepatic Impairment only&#xD;
&#xD;
          -  Severe ascites at Screening;&#xD;
&#xD;
          -  History of or current severe hepatic encephalopathy (Grade 3 or higher)&#xD;
&#xD;
          -  Any of the following laboratory parameters at screening:&#xD;
&#xD;
               1. Serum ALT &gt; 5 × the upper limit of normal range (ULN);&#xD;
&#xD;
               2. Serum albumin &lt; 2.4 g/dL;&#xD;
&#xD;
               3. Platelet count &lt; 80,000/mm3;&#xD;
&#xD;
               4. Hemoglobin &lt; 11 g/dL;&#xD;
&#xD;
               5. Absolute neutrophil count (ANC) &lt; 1.5 × 109/L (&lt; 1.5 × 103/μL);&#xD;
&#xD;
          -  Biliary liver cirrhosis or other causes of HI not related to parenchymal disorder&#xD;
             and/or disease of the liver, including hepatocellular carcinoma.&#xD;
&#xD;
        Additional exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc Cantillon, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Kyowa Hakko Kirin Pharma, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amy Zhang, PhD.</last_name>
    <role>Study Director</role>
    <affiliation>Kyowa Hakko Kirin Pharma, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Noccr/Vrg</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>May 19, 2015</last_update_submitted>
  <last_update_submitted_qc>May 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 21, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mild hepatic impairment</keyword>
  <keyword>Healthy volunteer</keyword>
  <keyword>Istradefylline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Istradefylline</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/NCT02256033
org study id: 6002-016
nct id: NCT02256033
lead sponsor: 
has dmc: No
The purpose of this study is to test whether mild liver impairment affects blood levels of
      istradefylline in humans. Decreased liver function could possibly increase istradefylline
      levels.
This is a multicenter, open-label, parallel group, single-dose study to determine the
      single-dose PK of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh
      Class A) and in subjects with normal hepatic function. Ten subjects with mild HI (Child-Pugh
      Class A) and 10 subjects with normal hepatic function (matched for age, gender, race, and
      BMI) will be enrolled. Enrollment of the subjects with normal hepatic function will be
      subsequent to the HI subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Comparison of pharmacokinetic parameter istradefylline (Area under the concentration-time curve [AUC]) between subjects with hepatic impairment and healthy subjects with normal hepatic function using an analysis of variance model
time frame: Intermittently for a total of 36 days
description: Single-dose pharmacokinetics (PK) of istradefylline in subjects with mild hepatic impairment (HI) (Child-Pugh Class A) and in subjects with normal hepatic function
measure: Number of adverse events and serious adverse events
time frame: Continuously for 36 days
description: Safety and tolerability will be assessed through review of recorded adverse events and serious adverse events.
arm group label: Istradefylline
arm group type: Experimental
description: One 40-mg tablet of istradefylline administered on Day 1.
intervention type: Drug
intervention name: Istradefylline
description: One 40 mg-tablet administered on Day 1
arm group label: Istradefylline
other name: KW-6002
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marc Cantillon, M.D.
role: Study Chair
affiliation: Kyowa Hakko Kirin Pharma, Inc.
last name: Amy Zhang, PhD.
role: Study Director
affiliation: Kyowa Hakko Kirin Pharma, Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Istradefylline