<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/NCT02243241</url>
  </required_header>
  <id_info>
    <org_study_id>HYD1009</org_study_id>
    <nct_id>NCT02243241</nct_id>
  </id_info>
  <brief_title>The Effect of Hydrocodone Bitartrate (HYD) Extended-Release Tablets on QT /QTc Intervals in Healthy Adult Subjects</brief_title>
  <official_title>A Randomized, Double-blind, Placebo- and Positive-Controlled, Parallel Group, Dose Escalating Study of the Effect of Hydrocodone Bitartrate (HYD) Extended-Release Tablets at Doses up to 160 mg on QT/QTc in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Purdue Pharma LP</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Purdue Pharma LP</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluate the effect of multiple doses (once daily for 3 days each of HYD 80, 120, and 160 mg&#xD;
      tablets) on the QT/QTc interval.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</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>Parallel Assignment</intervention_model>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 9</time_frame>
    <description>The electrocardiogram (ECG) effects of HYD 80 mg (day 9) on the QT/QTc interval</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 12</time_frame>
    <description>The ECG effects of HYD 120 mg (day 12) on the QT/QTc interval</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The ECG effects of HYD 160 mg (day 15) on the QT/QTc interval</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 9</time_frame>
    <description>The ECG effects of moxifloxacin (day 9) on the QT/QTc interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 12</time_frame>
    <description>The ECG effects of moxifloxacin (day 12) on the QT/QTc interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The ECG effects of moxifloxacin (day 15) on the QT/QTc interval</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">208</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>HYD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxifloxacin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Moxifloxacin is the positive control.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for HYD and placebo for moxifloxacin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HYD</intervention_name>
    <description>Hydrocodone bitartrate 80 mg (day 9), 120 mg (day 12), 160 mg [(1) 40 mg tablet + (1) 120 mg tablet] (day 15) extended-release tablets administered orally every 24 hours.</description>
    <arm_group_label>HYD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>Moxifloxacin 400 mg tablets administered orally on the morning of day 9, day 12, and day 15 only.</description>
    <arm_group_label>Moxifloxacin</arm_group_label>
    <other_name>Avelox®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for HYD</intervention_name>
    <description>Placebo to match HYD tablets administered orally every 24 hours.</description>
    <arm_group_label>Moxifloxacin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for moxifloxacin</intervention_name>
    <description>Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.</description>
    <arm_group_label>HYD</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provide written informed consent;&#xD;
&#xD;
          -  Body weight ranging from 50 to 100 kilograms (kg) [110 to 220 pounds] and body mass&#xD;
             index (BMI) of 18 to 30 (kg/m2);&#xD;
&#xD;
          -  Males and females aged 18 to 50 years;&#xD;
&#xD;
          -  Willing to eat the food supplied during the study;&#xD;
&#xD;
          -  Willing to refrain from strenuous exercise through the end-of-study visit. Subjects&#xD;
             did not begin a new exercise program nor participate in any unusually strenuous&#xD;
             physical exertion;&#xD;
&#xD;
          -  Healthy and free of significant abnormal findings as determined by medical history,&#xD;
             physical examination, clinical laboratory values, vital signs, and safety 12-lead ECG;&#xD;
&#xD;
          -  Females of childbearing potential must use an adequate and reliable method of&#xD;
             contraception (ie, barrier with additional spermicidal foam or jelly, intra-uterine&#xD;
             device, hormonal contraception). Females who are postmenopausal must be postmenopausal&#xD;
             for ≥ 1 year and have elevated serum follicle stimulating hormone (FSH).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are pregnant (positive beta human chorionic gonadotropin test) or&#xD;
             lactating;&#xD;
&#xD;
          -  Current or recent (within 5 years) history of drug or alcohol abuse;&#xD;
&#xD;
          -  History or any current conditions that may interfere with drug absorption,&#xD;
             distribution, metabolism, or excretion;&#xD;
&#xD;
          -  Use of an opioid-containing medication in the past 30 days preceding the initial dose&#xD;
             in this study;&#xD;
&#xD;
          -  Known allergy to hydrocodone, opioids, psychotropic or hypnotic drugs, moxifloxacin,&#xD;
             or any member of the quinolone class drugs;&#xD;
&#xD;
          -  Any history of frequent nausea or emesis regardless of etiology;&#xD;
&#xD;
          -  Any history of seizures or head trauma with sequelae;&#xD;
&#xD;
          -  Participation in a clinical drug study during the 30 days preceding the initial dose&#xD;
             of study drug in this study;&#xD;
&#xD;
          -  Use of any medication including thyroid hormonal therapy (hormonal contraception and&#xD;
             hormonal replacement therapy in the form of estrogen with or without progestin is&#xD;
             allowed), vitamins, herbal and/or mineral supplements during the 7 days preceding the&#xD;
             initial dose of study drug;&#xD;
&#xD;
          -  Any significant illness during the 30 days preceding the initial dose of study drug in&#xD;
             this study;&#xD;
&#xD;
          -  Any personal or family history of prolonged QT interval or disorders of cardiac&#xD;
             rhythm;&#xD;
&#xD;
          -  Abnormal cardiac conditions including hypertension;&#xD;
&#xD;
          -  Abnormal cardiac condition denoted by any of the following:&#xD;
&#xD;
               -  QT data corrected for heart rate using the Fridericia formula (QTcF) interval&#xD;
                  &gt;450 milliseconds (msec)&#xD;
&#xD;
               -  PR interval &gt;240 msec or QRS &gt;110 msec&#xD;
&#xD;
               -  Evidence of second- or third-degree atrioventricular block&#xD;
&#xD;
               -  Pathological Q-waves (defined as Q-wave &gt;40 msec or depth &gt;0.5 millivolts [mV])&#xD;
&#xD;
               -  Evidence of ventricular pre-excitation, complete left bundle branch block (LBBB),&#xD;
                  right bundle branch block (RBBB), or incomplete RBBB&#xD;
&#xD;
               -  With a resting heart rate (HR) outside the range of 40 to 90 beats per minute&#xD;
                  (bpm);&#xD;
&#xD;
          -  Abnormalities on physical examination, vital signs, safety 12-lead ECG, or clinical&#xD;
             laboratory values, unless those abnormalities are judged clinically insignificant by&#xD;
             the investigator;&#xD;
&#xD;
          -  Oxygen saturation &lt;94% as measured by pulse oximetry (SpO2);&#xD;
&#xD;
          -  Refusal to abstain completely from caffeine or xanthine during confinement;&#xD;
&#xD;
          -  Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial&#xD;
             study drug administration through the end-of-study visit;&#xD;
&#xD;
          -  Blood or blood products donated within 30 days prior to initial study drug&#xD;
             administration or any time through the end-of-study visit, except as required by the&#xD;
             study protocol;&#xD;
&#xD;
          -  History of smoking or use of nicotine products within 45 days of initial study drug&#xD;
             administration or a positive urine cotinine test;&#xD;
&#xD;
          -  Positive results of urine drug screen or alcohol screen;&#xD;
&#xD;
          -  Positive results of hepatitis B surface antigen (HBsAg), hepatitis C antibody&#xD;
             (anti-HCV);&#xD;
&#xD;
          -  Presence of Gilbert's Syndrome or any known hepatobiliary abnormalities;&#xD;
&#xD;
          -  The investigator believes the subject to be unsuitable for reason(s) not specifically&#xD;
             stated in the exclusion criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>PPD Phase I Clinic</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 15, 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>September 15, 2014</last_update_submitted>
  <last_update_submitted_qc>September 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy volunteers</keyword>
  <keyword>Opioid</keyword>
  <keyword>ECG</keyword>
  <keyword>QTcI</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Norgestimate, ethinyl estradiol drug combination</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/NCT02243241
org study id: HYD1009
nct id: NCT02243241
lead sponsor: 
has dmc: No
Evaluate the effect of multiple doses (once daily for 3 days each of HYD 80, 120, and 160 mg
      tablets) on the QT/QTc interval.
allocation: Randomized
intervention model: Parallel Assignment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 9
description: The electrocardiogram (ECG) effects of HYD 80 mg (day 9) on the QT/QTc interval
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 12
description: The ECG effects of HYD 120 mg (day 12) on the QT/QTc interval
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 15
description: The ECG effects of HYD 160 mg (day 15) on the QT/QTc interval
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 9
description: The ECG effects of moxifloxacin (day 9) on the QT/QTc interval
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 12
description: The ECG effects of moxifloxacin (day 12) on the QT/QTc interval
measure: The time-matched analysis on QT data (change from baseline, placebo-subtracted) corrected for heart rate (QTc), based on an individual correction (QTcI) method
time frame: Baseline and Day 15
description: The ECG effects of moxifloxacin (day 15) on the QT/QTc interval
arm group label: HYD
arm group type: Experimental
arm group label: Moxifloxacin
arm group type: Other
description: Moxifloxacin is the positive control.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for HYD and placebo for moxifloxacin
intervention type: Drug
intervention name: HYD
description: Hydrocodone bitartrate 80 mg (day 9), 120 mg (day 12), 160 mg [(1) 40 mg tablet + (1) 120 mg tablet] (day 15) extended-release tablets administered orally every 24 hours.
arm group label: HYD
intervention type: Drug
intervention name: Moxifloxacin
description: Moxifloxacin 400 mg tablets administered orally on the morning of day 9, day 12, and day 15 only.
arm group label: Moxifloxacin
other name: Avelox®
intervention type: Drug
intervention name: Placebo for HYD
description: Placebo to match HYD tablets administered orally every 24 hours.
arm group label: Moxifloxacin
arm group label: Placebo
intervention type: Drug
intervention name: Placebo for moxifloxacin
description: Placebo to match moxifloxacin tablets administered orally on the mornings of day 9, day 12, and day 15 only.
arm group label: HYD
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: Norgestimate, ethinyl estradiol drug combination