<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/NCT02242734</url>
  </required_header>
  <id_info>
    <org_study_id>ZX002-1001</org_study_id>
    <nct_id>NCT02242734</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics and Metabolism of Hydrocodone Bitartrate Controlled-Release (HC-CR) in Subjects With Hepatic Impairment</brief_title>
  <official_title>Evaluation of the Effect of Hepatic Impairment on the Pharmacokinetics and Metabolism of Hydrocodone and Its Metabolites Following Administration of Hydrocodone Bitartrate Extended-Release (HC-ER) 20mg Capsules</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zogenix, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UCB Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine the influence of hepatic impairment on the pharmacokinetics and metabolism of&#xD;
      Hydrocodone Bitartrate Extended-Release (HC-ER) 20 mg capsules&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pharmacokinetics and relative bioavailability of hydrocodone and its metabolites under fasted&#xD;
      conditions&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2011</start_date>
  <completion_date type="Actual">May 2011</completion_date>
  <primary_completion_date type="Actual">May 2011</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic profile of hydrocodone and its metabolites of 20 mg HC-ER</measure>
    <time_frame>Day 1-3</time_frame>
    <description>PK parameters including Cmax, Tmax, , AUC 0-t, AUC 0-inf, T1/2 and Kel</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Mild Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mg HC-ER</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mg HC-ER</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mg HC-ER</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20 mg HC-ER</intervention_name>
    <description>1-72 hours</description>
    <arm_group_label>Mild Hepatic Impairment</arm_group_label>
    <other_name>Zohydro ER</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20 mg HC-ER</intervention_name>
    <description>1-72 hours</description>
    <arm_group_label>Moderate Hepatic Impairment</arm_group_label>
    <other_name>Zohydro ER</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20 mg HC-ER</intervention_name>
    <description>1-72 hours</description>
    <arm_group_label>No Hepatic Impairment</arm_group_label>
    <other_name>Zohydro ER</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All hepatically-impaired subjects must have meet all of the following inclusion&#xD;
             criteria to be enrolled into the study:&#xD;
&#xD;
          2. Male or non-pregnant, non-lactating females. Subjects were aged 18-80 years,&#xD;
             inclusive.&#xD;
&#xD;
          3. Subjects must have been a clinical diagnosis of chronic hepatic impairment for&#xD;
             duration of at least 6 months classified as mild or moderate as per Child-Pugh&#xD;
             classification.&#xD;
&#xD;
          4. Hepatic insufficiency was stable with no acute episodes of illness within the previous&#xD;
             2 months due to deterioration of hepatic function due to any etiology.&#xD;
&#xD;
          5. Female subjects of childbearing potential including those who had a tubal ligation&#xD;
             surgery but excluded those who did not have a menstrual period for a minimum of 2&#xD;
             years, had a negative pregnancy test at the Screening and Day -1 visits, and consented&#xD;
             to use a medically-acceptable method of contraception throughout the entire study&#xD;
             period and for 1 week after the study completed. Medically acceptable methods of&#xD;
             contraception included were not limited to abstinence, birth control pills or patches,&#xD;
             vaginal rings, diaphragm with vaginal spermicide, Intrauterine Device, and progestin&#xD;
             implant or injection (used consistently for 3 months prior to study dosing).&#xD;
&#xD;
          6. Subjects voluntarily provided written informed consent.&#xD;
&#xD;
          7. Subjects, in the Investigator's opinion, were able to complete study procedures&#xD;
&#xD;
               -  All healthy control subjects must have met all hepatic subject inclusion criteria&#xD;
                  as outlined above with the exception of Inclusion Criteria 3 &amp; 4 above which&#xD;
                  should be substituted with the following to be enrolled into the study:&#xD;
&#xD;
               -  Must have been matched by age (±10 years) and Body Mass Index (BMI) (± 10% of&#xD;
                  BMI) with some consideration for race and gender to subjects with hepatic&#xD;
                  impairment.&#xD;
&#xD;
               -  Were medically healthy with no clinically significant abnormalities in their&#xD;
                  laboratory profile as deemed by the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who were pregnant or breastfeeding&#xD;
&#xD;
          2. Any clinically significant condition that would, in the opinion of the Investigator,&#xD;
             preclude study participation&#xD;
&#xD;
          3. Uncontrolled blood pressure, i.e., subject has a sitting systolic blood pressure 180&#xD;
             mmHg or 90 mmHg, and/or a sitting diastolic blood pressure 120 mmHg or 50 mmHg at&#xD;
             Screening.&#xD;
&#xD;
          4. Body Mass Index (BMI) &gt;40 kg/m2.&#xD;
&#xD;
          5. Known allergy or hypersensitivity to hydrocodone, or other opioids.&#xD;
&#xD;
          6. Had taken any investigational drug within 30 days prior to the Day 1 Visit or&#xD;
             currently enrolled in another investigational drug study.&#xD;
&#xD;
          7. Had used a monoamine oxidase inhibitor within 14 days prior to Day 1.&#xD;
&#xD;
          8. Been taking opioids during the 30 days prior to Day 1 or needing to take opioids&#xD;
             during the study period&#xD;
&#xD;
          9. Positive for human immunodeficiency virus (HIV). Healthy control subjects must not&#xD;
             have been hepatitis C virus (HCV) positive, hepatically-impaired subjects could be HCV&#xD;
             positive but should not have been receiving treatment.&#xD;
&#xD;
         10. History of any illicit substance abuse in the past 2 years or any history of opioid&#xD;
             abuse. Subjects should not have been current abusers of alcohol and must have had a&#xD;
             negative serum alcohol level at Screening and Day -1.&#xD;
&#xD;
         11. Positive quantitative urine drug screen for illicit drugs, or non-prescribed&#xD;
             controlled substances at Screening.&#xD;
&#xD;
         12. Had made a plasma donation within 7 days prior to Day 1.&#xD;
&#xD;
         13. Had made any significant donation or loss of blood within 56 days prior to Day 1.&#xD;
&#xD;
         14. Had taken CYP2D6 and/or CYP3A4 inhibitors within 7 days prior to Day 1 and/or CYP2D6&#xD;
             and/or CYP3A4 inducers within 21 days prior to Day 1.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kenneth Lasseter, MD</last_name>
    <role>Study Director</role>
    <affiliation>Zogenix, Inc.</affiliation>
  </overall_official>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>November 8, 2022</last_update_submitted>
  <last_update_submitted_qc>November 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2022</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>Liver Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocodone</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/NCT02242734
org study id: ZX002-1001
nct id: NCT02242734
lead sponsor: 
has dmc: No
Determine the influence of hepatic impairment on the pharmacokinetics and metabolism of
      Hydrocodone Bitartrate Extended-Release (HC-ER) 20 mg capsules
Pharmacokinetics and relative bioavailability of hydrocodone and its metabolites under fasted
      conditions
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetic profile of hydrocodone and its metabolites of 20 mg HC-ER
time frame: Day 1-3
description: PK parameters including Cmax, Tmax, , AUC 0-t, AUC 0-inf, T1/2 and Kel
arm group label: Mild Hepatic Impairment
arm group type: Experimental
description: 20 mg HC-ER
arm group label: Moderate Hepatic Impairment
arm group type: Experimental
description: 20 mg HC-ER
arm group label: No Hepatic Impairment
arm group type: Experimental
description: 20 mg HC-ER
intervention type: Drug
intervention name: 20 mg HC-ER
description: 1-72 hours
arm group label: Mild Hepatic Impairment
other name: Zohydro ER
intervention type: Drug
intervention name: 20 mg HC-ER
description: 1-72 hours
arm group label: Moderate Hepatic Impairment
other name: Zohydro ER
intervention type: Drug
intervention name: 20 mg HC-ER
description: 1-72 hours
arm group label: No Hepatic Impairment
other name: Zohydro ER
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kenneth Lasseter, MD
role: Study Director
affiliation: Zogenix, Inc.
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Hydrocodone