<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/NCT02207699</url>
  </required_header>
  <id_info>
    <org_study_id>B3551003</org_study_id>
    <secondary_id>BT-10-02</secondary_id>
    <nct_id>NCT02207699</nct_id>
  </id_info>
  <brief_title>Evaluation of the Effect of Benzonatate on QT Intervals Following Single Dose Administration of Benzonatate to Healthy Volunteers</brief_title>
  <official_title>Evaluation of the Effect of Benzonatate on QT Intervals Following Single Dose Administration of Benzonatate to Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the effects of benzonatate (200 mg and&#xD;
      800 mg) on the QT interval following single dose oral administration at each time point&#xD;
      post-dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fridericia-corrected QTc change from the pre-dose time point to the post-dose time points following administration of study drug in therapeutic (200 mg) and supratherapeutic doses (800 mg).</measure>
    <time_frame>-1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>QT interval for Benzonatate, 4-(butylamino)benzoic acid (BBA-major metabolite of benzonatate), and moxifloxacin.</measure>
    <time_frame>-1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PR interval, QRS complex from single 12-lead electrocardiogram (ECG)</measure>
    <time_frame>Screening, Day 0, and Day 1 at 4, 8, and 24 hours after dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum plasma concentration) for BT and BBA measured in mcg/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (time of maximum plasma concentration) for BT and BBA measured in minutes</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½ (terminal half-life) for BT and BBA measured in minutes</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast for BT and BBA measured in mcg•hr/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf for BT and BBA measured in mcg•hr/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax(dn) for BT and BBA measured in mcg/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast(dn) for BT and BBA measured in mcg•hr/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf(dn) for BT and BBA measured in mcg•hr/mL</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F for BT measured in L/hr</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F for BT measured in L</measure>
    <time_frame>0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Benzonatate 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Benzonatate 800 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Moxifloxacin 400 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Benzonatate 200 mg</intervention_name>
    <description>2 benzonatate 100 mg perles and 6 placebo perles give by mouth once</description>
    <arm_group_label>Benzonatate 200 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Benzonatate 800 mg</intervention_name>
    <description>8 benzonatate 100 mg perles given by mouth once</description>
    <arm_group_label>Benzonatate 800 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin 400 mg</intervention_name>
    <description>1 moxifloxacin 400 mg tablet given by mouth once</description>
    <arm_group_label>Moxifloxacin 400 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>8 placebo perles given by mouth once</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female subjects between the ages of 18 and 55 years, inclusive.&#xD;
             Healthy is defined as no clinically relevant abnormalities identified by a detailed&#xD;
             medical history, full physical examination, including blood pressure and pulse rate&#xD;
             measurement, 12- lead ECG and clinical laboratory tests.&#xD;
&#xD;
          -  Female subjects of non-childbearing potential must meet at least one of the following&#xD;
             criteria:&#xD;
&#xD;
               1. Achieved postmenopausal status, defined as: cessation of regular menses for at&#xD;
                  least 12 consecutive months with no alternative pathological or physiological&#xD;
                  cause; and have a serum FSH level within the laboratory's reference range for&#xD;
                  postmenopausal females;&#xD;
&#xD;
               2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;&#xD;
&#xD;
               3. Have medically confirmed ovarian failure. All other female subjects (including&#xD;
                  females with tubal ligations and females that do NOT have a documented&#xD;
                  hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered&#xD;
                  to be of childbearing potential.&#xD;
&#xD;
          -  Body mass index (BMI) of 17.5 to 30.5 kg/m2, inclusive, and a total body weight &gt;50 kg&#xD;
             (110 lb).&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all aspects of the study.&#xD;
&#xD;
          -  Subjects willing and able to comply with scheduled visits, treatment plan, laboratory&#xD;
             tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant ECG abnormality at screening as determined by the investigator.&#xD;
&#xD;
          -  History or risk factors of QT prolongation or torsades de pointes, congenital deafness&#xD;
             and family history of sudden death.&#xD;
&#xD;
          -  12-lead ECG demonstrating QTcF &gt;450 msec or a QRS interval &gt;110 msec at Screening.&#xD;
&#xD;
          -  Use of medications or dietary supplements capable of inducing or inhibiting hepatic&#xD;
             enzyme metabolism or transport (e.g., barbiturates, rifampin, carbamazepine,&#xD;
             phenytoin, primidone, or St. John's Wort) within 28 days of the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Consumption of grapefruit or grapefruit containing products within 7 days prior to the&#xD;
             first dose of study medication.&#xD;
&#xD;
          -  Known history of hypersensitivity, allergy, severe adverse drug reaction or&#xD;
             intolerance to quinolone antibiotics.&#xD;
&#xD;
          -  Known hypersensitivity to benzonatate or other ester-type local anesthetics (ie,&#xD;
             tetracaine, procaine).&#xD;
&#xD;
          -  Subjects with a presence or history of dysphagia or difficulty swallowing pills.&#xD;
&#xD;
          -  Subjects taking any concomitant anticonvulsant medications or with a history of&#xD;
             seizure disorder.&#xD;
&#xD;
          -  Subjects with a positive response to the question of actual attempt in the suicidal&#xD;
             behavior section of the C-SSRS (Columbia-Suicide Severity Rating Scale). Subjects with&#xD;
             active suicidal ideation with intent to act within 6 months of screening as determined&#xD;
             by a positive response to questions 4 or 5 in the suicidal ideation section of the&#xD;
             C-SSRS.&#xD;
&#xD;
          -  Screening laboratory values considered clinically significant by the investigator.&#xD;
&#xD;
          -  Screening supine blood pressure ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic),&#xD;
             following at least 5 minutes of rest.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pfizer Investigational Site</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3551003&amp;StudyName=Benzonatate%20QTc</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>June 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>July 31, 2014</last_update_submitted>
  <last_update_submitted_qc>July 31, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 4, 2014</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>Moxifloxacin</mesh_term>
    <mesh_term>Benzonatate</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/NCT02207699
org study id: B3551003
secondary id: BT-10-02
nct id: NCT02207699
lead sponsor: 
has dmc: No
The primary objective of this study is to determine the effects of benzonatate (200 mg and
      800 mg) on the QT interval following single dose oral administration at each time point
      post-dose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Fridericia-corrected QTc change from the pre-dose time point to the post-dose time points following administration of study drug in therapeutic (200 mg) and supratherapeutic doses (800 mg).
time frame: -1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours
measure: QT interval for Benzonatate, 4-(butylamino)benzoic acid (BBA-major metabolite of benzonatate), and moxifloxacin.
time frame: -1, -0.75, -0.5, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours
measure: PR interval, QRS complex from single 12-lead electrocardiogram (ECG)
time frame: Screening, Day 0, and Day 1 at 4, 8, and 24 hours after dosing
measure: Cmax (maximum plasma concentration) for BT and BBA measured in mcg/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: Tmax (time of maximum plasma concentration) for BT and BBA measured in minutes
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: t½ (terminal half-life) for BT and BBA measured in minutes
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: AUClast for BT and BBA measured in mcg•hr/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: AUCinf for BT and BBA measured in mcg•hr/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: Cmax(dn) for BT and BBA measured in mcg/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: AUClast(dn) for BT and BBA measured in mcg•hr/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: AUCinf(dn) for BT and BBA measured in mcg•hr/mL
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: CL/F for BT measured in L/hr
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
measure: Vz/F for BT measured in L
time frame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 12 hours
arm group label: Benzonatate 200 mg
arm group type: Experimental
arm group label: Benzonatate 800 mg
arm group type: Experimental
arm group label: Moxifloxacin 400 mg
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Benzonatate 200 mg
description: 2 benzonatate 100 mg perles and 6 placebo perles give by mouth once
arm group label: Benzonatate 200 mg
intervention type: Drug
intervention name: Benzonatate 800 mg
description: 8 benzonatate 100 mg perles given by mouth once
arm group label: Benzonatate 800 mg
intervention type: Drug
intervention name: Moxifloxacin 400 mg
description: 1 moxifloxacin 400 mg tablet given by mouth once
arm group label: Moxifloxacin 400 mg
intervention type: Drug
intervention name: Placebo
description: 8 placebo perles given by mouth once
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: United States
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3551003&StudyName=Benzonatate%20QTc
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: Benzonatate