<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/NCT02222740</url>
  </required_header>
  <id_info>
    <org_study_id>ELN154088-203</org_study_id>
    <nct_id>NCT02222740</nct_id>
  </id_info>
  <brief_title>A Safety, Tolerability and Pharmacokinetic Dose Escalation Study of HC-ER in Patients With Osteoarthritis Pain</brief_title>
  <official_title>A Multiple-Dose, Safety, Tolerability, and Pharmacokinetic Dose-Escalation Study of Hydrocodone Bitartrate Extended Release (HC-ER) in Patients With Chronic, Moderate to Severe Osteoarthritis Pain</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>
      Assess the safety, tolerability and pharmacokinetics of multiple doses of 10, 20, 30, and 40&#xD;
      mg of Hydrocodone Bitartrate Extended Release (HC-ER)capsules taken with food at steady&#xD;
      state, in subjects with chronic, moderate to severe osteoarthritis (OA) pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Safety parameters assessed included adverse events, physical examinations, vital signs,&#xD;
      12-lead electrocardiogram (ECGs), clinical laboratory testing and overall Arthritis Pain&#xD;
      Intensity and opioid side effects&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2002</start_date>
  <completion_date type="Actual">December 2002</completion_date>
  <primary_completion_date type="Actual">December 2002</primary_completion_date>
  <phase>Phase 2</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>Assess the steady-state pharmacokinetics (PK) of multiple dose of 10, 20, 30, and 40 mg of HC-ER</measure>
    <time_frame>Day 1-28</time_frame>
    <description>PK parameters including Tmax, Cmax and Cmin were calculated for each dose level in each group from the PK profile of hydrocodone and the metabolites hydromorphone, and norhydrocodone.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Osteoarthrosis</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice per day (BID) for 7 days, followed by 20 mg BID for 7 days, followed by 30 mg BID for 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice Per Day (BID) for 7 days, followed by 30 mg BID for 7 days, followed by 40 mg BID for 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)</intervention_name>
    <description>Schedule II Class</description>
    <arm_group_label>Group 1</arm_group_label>
    <other_name>Zohydro ER</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)</intervention_name>
    <description>Schedule II Class</description>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Zohydro ER</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects were 18 years or older&#xD;
&#xD;
          -  Subjects had osteoarthritis (OA) defined by:&#xD;
&#xD;
        Presence of of typical hip and/or knee joint symptoms. Involvement of at least 1 hip or&#xD;
        knee joints that had warranted treatment with Non-Steroidal Anti-Inflammatory Drugs&#xD;
        (NSAIDs), including cyclooxygenase-2 [COX-2] inhibitors and/or acetaminophen (APAP) for the&#xD;
        last 3 months.&#xD;
&#xD;
        Radiographic evidence within the last 6 months of OA in the index joint, with Grade II to&#xD;
        IV severity, as illustrated by the Atlas of Standard Radiographs.&#xD;
&#xD;
          -  Subjects were otherwise in generally good health, as determined by the investigator,&#xD;
             on the basis of medical history, physical examination, electrocardiogram (ECG), and&#xD;
             screening laboratory results.&#xD;
&#xD;
          -  Female subjects were either physically incapable of childbearing or were practicing an&#xD;
             acceptable method of birth control and had a negative pregnancy test result&#xD;
             demonstrated before dosing.&#xD;
&#xD;
          -  Subjects had experienced a suboptimal response to APAP and NSAID therapy (including&#xD;
             COX-2 inhibitor).&#xD;
&#xD;
          -  Subjects had used opioids for OA pain on an as needed (PRN) or occasional basis.&#xD;
&#xD;
          -  Subjects were willing and able to discontinue or modify their current medication used&#xD;
             for management of OA pain per protocol.&#xD;
&#xD;
          -  Subjects had steady, not transient, pain and a categorical pain rating of moderate to&#xD;
             severe on a scale of none, mild, moderate, or severe.&#xD;
&#xD;
          -  Subjects weighed &gt; or = to100 lbs.&#xD;
&#xD;
          -  If a subject had taken any inducers or inhibitors of cytochrome P450 [CYP450j), these&#xD;
             were discontinued and an appropriate washout period (5 half-lives) had occurred before&#xD;
             entry in the study.&#xD;
&#xD;
          -  Subjects were able to take oral medication and were willing to comply with the&#xD;
             protocol.&#xD;
&#xD;
          -  Subjects agreed to abstain from alcohol consumption for the duration of the study.&#xD;
&#xD;
          -  Subjects were able to read, understand, and voluntarily sign the IRB approved consent&#xD;
             document before the performance of any study-specific procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects had any clinically significant condition that would, in the investigator's&#xD;
             opinion, preclude study participation.&#xD;
&#xD;
          -  Subjects had any other clinically significant form of disease at the index joint&#xD;
             (study joint) or had been diagnosed with inflammatory arthritis, gout, pseudo-gout,&#xD;
             Paget's disease, or any other chronic pain syndrome that, in the investigator's&#xD;
             opinion, might interfere with the assessment of pain and other symptoms of OA.&#xD;
&#xD;
          -  Subjects had known allergies or previous, significant reactions to opioids.&#xD;
&#xD;
          -  Subjects had any laboratory abnormality at screening that was considered clinically&#xD;
             significant by the investigator, or that, in the opinion of the investigator, would&#xD;
             have contraindicated study participation.&#xD;
&#xD;
          -  Subjects were known to have positive test results for human immunodeficiency virus&#xD;
             (HIV), hepatitis B antigen, or hepatitis C antibody.&#xD;
&#xD;
          -  Subjects had a history of chronic, scheduled opioid use for OA.&#xD;
&#xD;
          -  Subjects had any signs or symptoms of opioid withdrawal.&#xD;
&#xD;
          -  Subjects had a history of substance or alcohol abuse within 2 years before study&#xD;
             entry.&#xD;
&#xD;
          -  Subjects tested positively on a urine screen for drugs of abuse.&#xD;
&#xD;
          -  Subjects had received any steroid therapy (e.g., oral, intramuscular, intravenous, or&#xD;
             soft tissue) within 1 month of study entry.&#xD;
&#xD;
          -  Subjects had a condition that would contraindicate the use of opioid analgesia.&#xD;
&#xD;
          -  Subjects had participated in a study of an investigational drug or device, or had&#xD;
             donated blood, within 30 days before study entry.&#xD;
&#xD;
          -  Subjects used any medication that the investigator felt would interact unfavorably&#xD;
             with the study medication (e.g., potentiation of sedation with tricyclic&#xD;
             antidepressants).&#xD;
&#xD;
          -  Subjects had used opioid analgesics for more than 3 days during the 30 days before&#xD;
             screening.&#xD;
&#xD;
          -  Subjects had a history of seizures.&#xD;
&#xD;
          -  Subjects were considered by the investigator to be unsuitable for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 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>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</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/NCT02222740
org study id: ELN154088-203
nct id: NCT02222740
lead sponsor: 
has dmc: No
Assess the safety, tolerability and pharmacokinetics of multiple doses of 10, 20, 30, and 40
      mg of Hydrocodone Bitartrate Extended Release (HC-ER)capsules taken with food at steady
      state, in subjects with chronic, moderate to severe osteoarthritis (OA) pain.
Safety parameters assessed included adverse events, physical examinations, vital signs,
      12-lead electrocardiogram (ECGs), clinical laboratory testing and overall Arthritis Pain
      Intensity and opioid side effects
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Assess the steady-state pharmacokinetics (PK) of multiple dose of 10, 20, 30, and 40 mg of HC-ER
time frame: Day 1-28
description: PK parameters including Tmax, Cmax and Cmin were calculated for each dose level in each group from the PK profile of hydrocodone and the metabolites hydromorphone, and norhydrocodone.
arm group label: Group 1
arm group type: Experimental
description: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice per day (BID) for 7 days, followed by 20 mg BID for 7 days, followed by 30 mg BID for 7 days
arm group label: Group 2
arm group type: Experimental
description: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER) Twice Per Day (BID) for 7 days, followed by 30 mg BID for 7 days, followed by 40 mg BID for 7 days
intervention type: Drug
intervention name: 10 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
description: Schedule II Class
arm group label: Group 1
other name: Zohydro ER
intervention type: Drug
intervention name: 20 mg of Hydrocodone Bitartrate Extended Release (HC-ER)
description: Schedule II Class
arm group label: Group 2
other name: Zohydro ER
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Hydrocodone