<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/NCT01660893</url>
  </required_header>
  <id_info>
    <org_study_id>SR 3-01</org_study_id>
    <nct_id>NCT01660893</nct_id>
  </id_info>
  <brief_title>Comparison of Intranasal Kovacaine Mist, Tetracaine Alone, and Placebo for Anesthetizing Maxillary Teeth</brief_title>
  <official_title>A Phase III, Multi-Center, Randomized, Double-Blind, Parallel-Groups Clinical Trial Comparing the Efficacy and Safety of Intranasally Administered Kovacaine Mist to Tetracaine Alone and to Placebo for Anesthetizing Maxillary Teeth in Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Renatus, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Triligent International</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rho, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Renatus, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the efficacy of Kovacaine Mist, Tetracaine only, and&#xD;
      Placebo for inducing pulpal anesthesia of the maxillary teeth in adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will employ a multi-center, randomized, double-blind, placebo-controlled,&#xD;
      parallel-groups design to assess the safety and efficacy of Kovacaine Mist delivered&#xD;
      intranasally for inducing pulpal anesthesia of maxillary teeth numbers 4 to 13 (maxillary&#xD;
      right second premolar to maxillary left second premolar) sufficient to allow completion of&#xD;
      the Study Dental Procedure.&#xD;
&#xD;
      A total of 140 subjects, randomized 2:2:1 (Kovacaine Mist:Tetracaine alone:Placebo) will be&#xD;
      enrolled to achieve 125 completed subjects; a total of 50 Kovacaine Mist subjects, 50&#xD;
      tetracaine alone subjects and 25 placebo subjects. Recruitment will be from diverse dental&#xD;
      patient populations. At the two study sites, a balanced enrollment of 70 subjects each is&#xD;
      planned to allow for a potential 10% drop-out rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).</measure>
    <time_frame>at 15 minutes with a 3 minute window</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraoral Soft-tissue Anesthesia (Yes/no)</measure>
    <time_frame>at 15 minutes with a 3 minute window</time_frame>
    <description>Number of patients who reported no pain when incisive papilla and greater palatine foramen soft-tissue was tested with a probe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Heart Rate Higher Than 125 Bpm</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Heart Rate Lower Than 50 Bpm</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With an Increase From Baseline in Systolic Blood Pressure Greater Than or Equal to 25 mm Hg and to a Value Higher Than 160 mm Hg</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Decrease From Baseline in Systolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Higher Than 90 mm Hg</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</measure>
    <time_frame>at any time within 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure</measure>
    <time_frame>from baseline to 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Profile Over Time of Heart Rate</measure>
    <time_frame>from baseline to 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Sniff Test</measure>
    <time_frame>administered at approximately 24 hours after drug administration</time_frame>
    <description>The change from screening in the the distance from the nose (in centimeters) that a patient is able to detect the smell of an alcohol swab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Profile Over Time of Systolic Blood Pressure</measure>
    <time_frame>from baseline to 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Profile Over Time of Diastolic Blood Pressure</measure>
    <time_frame>from baseline to 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Maximum Change From Baseline in Heart Rate</measure>
    <time_frame>from baseline to 120 minutes following drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Anesthesia</condition>
  <arm_group>
    <arm_group_label>Kovacaine Mist, 3 sprays unilateral</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tetracaine Only, 3 sprays unilateral</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetracaine HCl 3%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, 3 sprays unilateral</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tetracaine HCl 3% and oxymetazoline HCl 0.05%</intervention_name>
    <description>3 unilateral intranasal sprays per dose</description>
    <arm_group_label>Kovacaine Mist, 3 sprays unilateral</arm_group_label>
    <other_name>Kovacaine Mist</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tetracaine HCl 3%</intervention_name>
    <description>3 unilateral intranasal sprays per dose</description>
    <arm_group_label>Tetracaine Only, 3 sprays unilateral</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>3 unilateral intranasal sprays per dose</description>
    <arm_group_label>Placebo, 3 sprays unilateral</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female 18 years of age or older.&#xD;
&#xD;
          -  Need for an operative restorative dental procedure requiring local anesthesia for a&#xD;
             single vital maxillary tooth (other than a maxillary first, second, or third molar)&#xD;
             with no evidence of pulpal pathology.&#xD;
&#xD;
          -  Normal lip, nose, eyelid, and cheek sensation.&#xD;
&#xD;
          -  Able to understand and sign the study informed consent document, communicate with the&#xD;
             investigators, and understand and comply with the requirements of the protocol.&#xD;
&#xD;
          -  Patency of the naris ipsilateral to the tooth undergoing the Study Dental Procedure.&#xD;
&#xD;
          -  Resting heart rate (HR) between 55 and 100 beats per minute (bpm), inclusive.&#xD;
&#xD;
          -  Seated systolic blood pressure (SBP) between 95 and 140 mm Hg, inclusive and seated&#xD;
             diastolic blood pressure (DBP) between 60 and 90 mm Hg, inclusive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inadequately controlled hypertension (blood pressure greater than 140/90 mm Hg).&#xD;
&#xD;
          -  Inadequately controlled active thyroid disease of any type.&#xD;
&#xD;
          -  Frequent nose bleeds (≥ 5 per month).&#xD;
&#xD;
          -  Having received dental care requiring a local anesthetic within the last 24 hours.&#xD;
&#xD;
          -  History of allergy to or intolerance of tetracaine, benzyl alcohol, other ester local&#xD;
             anesthetics, or para-aminobenzoic acid (as found in PABA-containing sunscreen).&#xD;
&#xD;
          -  History of allergy or hypersensitivity to articaine, oxymetazoline, epinephrine, or&#xD;
             sulfite preservatives.&#xD;
&#xD;
          -  Use of a monoamine oxidase inhibitor within the 3 weeks preceding study entry.&#xD;
&#xD;
          -  Nursing, pregnant, suspected of being pregnant, or trying to become pregnant. (Females&#xD;
             of child-bearing potential will be required to take a urine pregnancy test on the day&#xD;
             of, but prior to, study drug administration to rule out pregnancy.)&#xD;
&#xD;
          -  Having received any investigational drug and/or participation in any clinical trial&#xD;
             within 30 days prior to study participation.&#xD;
&#xD;
          -  Having used oxymetazoline or phenylephrine nasal spray, nasal irrigation, or other&#xD;
             nasal or oral decongestant on the day of the study procedure.&#xD;
&#xD;
          -  History of congenital or idiopathic methemoglobinemia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul A. Moore, DMD/PhD/MPH</last_name>
    <role>Study Director</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Maryland, Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>20740</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Family and Cosmetic Dentistry</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jean Brown Research</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <results_first_submitted>October 6, 2016</results_first_submitted>
  <results_first_submitted_qc>August 1, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">September 5, 2017</results_first_posted>
  <disposition_first_submitted>May 15, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>May 15, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">June 8, 2015</disposition_first_posted>
  <last_update_submitted>August 1, 2017</last_update_submitted>
  <last_update_submitted_qc>August 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>operative</keyword>
  <keyword>dental procedure</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylephrine</mesh_term>
    <mesh_term>Oxymetazoline</mesh_term>
    <mesh_term>Tetracaine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Kovacaine Mist, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="P2">
          <title>Tetracaine Only, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="P3">
          <title>Placebo, 3 Sprays Unilateral</title>
          <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Kovacaine Mist, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="B2">
          <title>Tetracaine Only, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="B3">
          <title>Placebo, 3 Sprays Unilateral</title>
          <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.3" spread="10.22"/>
                    <measurement group_id="B2" value="33.3" spread="11.10"/>
                    <measurement group_id="B3" value="32.7" spread="9.85"/>
                    <measurement group_id="B4" value="32.4" spread="10.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).</title>
        <time_frame>at 15 minutes with a 3 minute window</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Success</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Failure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intraoral Soft-tissue Anesthesia (Yes/no)</title>
        <description>Number of patients who reported no pain when incisive papilla and greater palatine foramen soft-tissue was tested with a probe</description>
        <time_frame>at 15 minutes with a 3 minute window</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Intraoral Soft-tissue Anesthesia (Yes/no)</title>
          <description>Number of patients who reported no pain when incisive papilla and greater palatine foramen soft-tissue was tested with a probe</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Incisive Papilla</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Greater Palatine Foramen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Heart Rate Higher Than 125 Bpm</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Heart Rate Higher Than 125 Bpm</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Heart Rate Lower Than 50 Bpm</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Heart Rate Lower Than 50 Bpm</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With an Increase From Baseline in Systolic Blood Pressure Greater Than or Equal to 25 mm Hg and to a Value Higher Than 160 mm Hg</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Increase From Baseline in Systolic Blood Pressure Greater Than or Equal to 25 mm Hg and to a Value Higher Than 160 mm Hg</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Decrease From Baseline in Systolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Decrease From Baseline in Systolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Higher Than 90 mm Hg</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Higher Than 90 mm Hg</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</title>
        <time_frame>at any time within 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure</title>
        <time_frame>from baseline to 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic Blood Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" spread="6.05"/>
                    <measurement group_id="O2" value="3.5" spread="8.34"/>
                    <measurement group_id="O3" value="1.2" spread="7.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic Blood Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" spread="5.35"/>
                    <measurement group_id="O2" value="4.5" spread="4.12"/>
                    <measurement group_id="O3" value="6.2" spread="8.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Profile Over Time of Heart Rate</title>
        <time_frame>from baseline to 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>The Profile Over Time of Heart Rate</title>
          <units>bpm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.9" spread="9.07"/>
                    <measurement group_id="O2" value="69.1" spread="7.95"/>
                    <measurement group_id="O3" value="81.0" spread="8.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.6" spread="8.3"/>
                    <measurement group_id="O2" value="67.1" spread="7.03"/>
                    <measurement group_id="O3" value="75.8" spread="8.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.6" spread="9.48"/>
                    <measurement group_id="O2" value="64.5" spread="6.36"/>
                    <measurement group_id="O3" value="NA" spread="NA">Data was not collected as study dental procedure was still ongoing</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.6" spread="8.65"/>
                    <measurement group_id="O2" value="64.3" spread="5.70"/>
                    <measurement group_id="O3" value="73.8" spread="8.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.3" spread="11.34"/>
                    <measurement group_id="O2" value="65.3" spread="8.31"/>
                    <measurement group_id="O3" value="70.2" spread="5.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.1" spread="7.74"/>
                    <measurement group_id="O2" value="64.3" spread="8.39"/>
                    <measurement group_id="O3" value="72.0" spread="7.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.4" spread="6.31"/>
                    <measurement group_id="O2" value="65.0" spread="8.43"/>
                    <measurement group_id="O3" value="70.8" spread="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Alcohol Sniff Test</title>
        <description>The change from screening in the the distance from the nose (in centimeters) that a patient is able to detect the smell of an alcohol swab.</description>
        <time_frame>administered at approximately 24 hours after drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Alcohol Sniff Test</title>
          <description>The change from screening in the the distance from the nose (in centimeters) that a patient is able to detect the smell of an alcohol swab.</description>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="5.44"/>
                    <measurement group_id="O2" value="0.8" spread="7.69"/>
                    <measurement group_id="O3" value="2.1" spread="2.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Profile Over Time of Systolic Blood Pressure</title>
        <time_frame>from baseline to 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>The Profile Over Time of Systolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.0" spread="8.23"/>
                    <measurement group_id="O2" value="116.1" spread="11.0"/>
                    <measurement group_id="O3" value="125.5" spread="6.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116.5" spread="6.82"/>
                    <measurement group_id="O2" value="114.2" spread="5.51"/>
                    <measurement group_id="O3" value="118.8" spread="8.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="123.0" spread="11.34"/>
                    <measurement group_id="O2" value="110.0" spread="4.24"/>
                    <measurement group_id="O3" value="NA" spread="NA">Data was not collected as study dental procedure was still ongoing</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="118.5" spread="9.26"/>
                    <measurement group_id="O2" value="113.6" spread="9.31"/>
                    <measurement group_id="O3" value="118.8" spread="10.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116.1" spread="9.68"/>
                    <measurement group_id="O2" value="113.3" spread="7.27"/>
                    <measurement group_id="O3" value="121.7" spread="12.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="117.7" spread="8.34"/>
                    <measurement group_id="O2" value="112.0" spread="6.93"/>
                    <measurement group_id="O3" value="119.7" spread="8.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.5" spread="10.89"/>
                    <measurement group_id="O2" value="113.7" spread="9.31"/>
                    <measurement group_id="O3" value="119.2" spread="9.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Profile Over Time of Diastolic Blood Pressure</title>
        <time_frame>from baseline to 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>The Profile Over Time of Diastolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.1" spread="5.09"/>
                    <measurement group_id="O2" value="73.0" spread="7.09"/>
                    <measurement group_id="O3" value="77.7" spread="7.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.9" spread="7.06"/>
                    <measurement group_id="O2" value="73.8" spread="5.65"/>
                    <measurement group_id="O3" value="75.5" spread="4.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.0" spread="6.96"/>
                    <measurement group_id="O2" value="70.0" spread="1.41"/>
                    <measurement group_id="O3" value="NA" spread="NA">Data was not collected as study dental procedure was still ongoing</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.4" spread="5.8"/>
                    <measurement group_id="O2" value="72.2" spread="6.03"/>
                    <measurement group_id="O3" value="74.2" spread="7.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.1" spread="6.62"/>
                    <measurement group_id="O2" value="75.9" spread="6.52"/>
                    <measurement group_id="O3" value="77.8" spread="7.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.5" spread="8.78"/>
                    <measurement group_id="O2" value="73.1" spread="6.40"/>
                    <measurement group_id="O3" value="78.8" spread="7.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 Minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.1" spread="10.91"/>
                    <measurement group_id="O2" value="72.1" spread="8.13"/>
                    <measurement group_id="O3" value="77.7" spread="8.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Maximum Change From Baseline in Heart Rate</title>
        <time_frame>from baseline to 120 minutes following drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Kovacaine Mist, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O2">
            <title>Tetracaine Only, 3 Sprays Unilateral</title>
            <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
          </group>
          <group group_id="O3">
            <title>Placebo, 3 Sprays Unilateral</title>
            <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Maximum Change From Baseline in Heart Rate</title>
          <units>bpm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="8.62"/>
                    <measurement group_id="O2" value="3.5" spread="7.09"/>
                    <measurement group_id="O3" value="2.3" spread="7.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 hours</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Kovacaine Mist, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3% and oxymetazoline HCl 0.05%&#xD;
Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="E2">
          <title>Tetracaine Only, 3 Sprays Unilateral</title>
          <description>Tetracaine HCl 3%&#xD;
Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose</description>
        </group>
        <group group_id="E3">
          <title>Placebo, 3 Sprays Unilateral</title>
          <description>Placebo&#xD;
Placebo: 3 unilateral intranasal sprays per dose</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <description>Tearing or watery eyes</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia eye</sub_title>
                <description>Numbness around eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oral discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anaesthetic Complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>Abnormal taste</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <description>Runny nose</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinalgia</sub_title>
                <description>Intranasal stinging or burning</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pharyngeal Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Intranasal Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Sharon M. Gordon</name_or_title>
      <organization>University of Maryland</organization>
      <phone>410-706-1656</phone>
      <email>sgordon@dental.umaryland.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01660893
org study id: SR 3-01
nct id: NCT01660893
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to compare the efficacy of Kovacaine Mist, Tetracaine only, and
      Placebo for inducing pulpal anesthesia of the maxillary teeth in adults.
The study will employ a multi-center, randomized, double-blind, placebo-controlled,
      parallel-groups design to assess the safety and efficacy of Kovacaine Mist delivered
      intranasally for inducing pulpal anesthesia of maxillary teeth numbers 4 to 13 (maxillary
      right second premolar to maxillary left second premolar) sufficient to allow completion of
      the Study Dental Procedure.

      A total of 140 subjects, randomized 2:2:1 (Kovacaine Mist:Tetracaine alone:Placebo) will be
      enrolled to achieve 125 completed subjects; a total of 50 Kovacaine Mist subjects, 50
      tetracaine alone subjects and 25 placebo subjects. Recruitment will be from diverse dental
      patient populations. At the two study sites, a balanced enrollment of 70 subjects each is
      planned to allow for a potential 10% drop-out rate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).
time frame: at 15 minutes with a 3 minute window
measure: Intraoral Soft-tissue Anesthesia (Yes/no)
time frame: at 15 minutes with a 3 minute window
description: Number of patients who reported no pain when incisive papilla and greater palatine foramen soft-tissue was tested with a probe
measure: Number of Participants With Heart Rate Higher Than 125 Bpm
time frame: at any time within 120 minutes following drug administration
measure: Number of Participants With Heart Rate Lower Than 50 Bpm
time frame: at any time within 120 minutes following drug administration
measure: Number of Participants With an Increase From Baseline in Systolic Blood Pressure Greater Than or Equal to 25 mm Hg and to a Value Higher Than 160 mm Hg
time frame: at any time within 120 minutes following drug administration
measure: Number of Participants With a Decrease From Baseline in Systolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg
time frame: at any time within 120 minutes following drug administration
measure: Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Higher Than 90 mm Hg
time frame: at any time within 120 minutes following drug administration
measure: Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg
time frame: at any time within 120 minutes following drug administration
measure: Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
time frame: from baseline to 120 minutes following drug administration
measure: The Profile Over Time of Heart Rate
time frame: from baseline to 120 minutes following drug administration
measure: Alcohol Sniff Test
time frame: administered at approximately 24 hours after drug administration
description: The change from screening in the the distance from the nose (in centimeters) that a patient is able to detect the smell of an alcohol swab.
measure: The Profile Over Time of Systolic Blood Pressure
time frame: from baseline to 120 minutes following drug administration
measure: The Profile Over Time of Diastolic Blood Pressure
time frame: from baseline to 120 minutes following drug administration
measure: Absolute Maximum Change From Baseline in Heart Rate
time frame: from baseline to 120 minutes following drug administration
arm group label: Kovacaine Mist, 3 sprays unilateral
arm group type: Experimental
description: Tetracaine HCl 3% and oxymetazoline HCl 0.05%
arm group label: Tetracaine Only, 3 sprays unilateral
arm group type: Experimental
description: Tetracaine HCl 3%
arm group label: Placebo, 3 sprays unilateral
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Tetracaine HCl 3% and oxymetazoline HCl 0.05%
description: 3 unilateral intranasal sprays per dose
arm group label: Kovacaine Mist, 3 sprays unilateral
other name: Kovacaine Mist
intervention type: Drug
intervention name: Tetracaine HCl 3%
description: 3 unilateral intranasal sprays per dose
arm group label: Tetracaine Only, 3 sprays unilateral
intervention type: Drug
intervention name: Placebo
description: 3 unilateral intranasal sprays per dose
arm group label: Placebo, 3 sprays unilateral
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul A. Moore, DMD/PhD/MPH
role: Study Director
affiliation: University of Pittsburgh
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Phenylephrine
mesh term: Oxymetazoline
mesh term: Tetracaine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 