<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/NCT03233737</url>
  </required_header>
  <id_info>
    <org_study_id>C-003</org_study_id>
    <nct_id>NCT03233737</nct_id>
  </id_info>
  <brief_title>Pain Study to Assess Local Anesthetic Efficacy and Safety of CTY-5339 on Gingival Mucosal Tissue in Normal Volunteers</brief_title>
  <official_title>A Double-blind, Cross-over, Incomplete Factorial Study to Assess the Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray (CTY-5339A) When Applied to the Gingival Mucosal Tissue in Normal Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cetylite Industries</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cetylite Industries</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if the topical application to gingival tissue of&#xD;
      the combination of benzocaine and tetracaine has a longer duration of local anesthetic&#xD;
      activity than benzocaine alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In a blinded study, either benzocaine alone or the combination of benzocaine and tetracaine&#xD;
      will be sprayed onto the gingival mucosal tissue. Onset and duration of local anesthesia will&#xD;
      be evaluated over a one hour period using pin prick and quantitative sensory testing of heat&#xD;
      (QST-heat) stimulation. Subjects will receive both treatments in a cross-over design with&#xD;
      each session separated by 4-14 days. A total of 50 subjects (normal volunteers) will be&#xD;
      evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2017</start_date>
  <completion_date type="Actual">February 20, 2018</completion_date>
  <primary_completion_date type="Actual">February 20, 2018</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stage II: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stage II: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stage I: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stage I: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage I outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stage II: Onset of Anesthesia for Pin Prick Test (PPT)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</measure>
    <time_frame>Any time within one hour post-application</time_frame>
    <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</measure>
    <time_frame>Any time within one hour post-application</time_frame>
    <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</measure>
    <time_frame>Time of application up to one hour post-application</time_frame>
    <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</measure>
    <time_frame>Time of application up to one hour post-application</time_frame>
    <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</measure>
    <time_frame>Any time within one hour post-application</time_frame>
    <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Onset of Anesthesia for Pin Prick Test (PPT)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</measure>
    <time_frame>Any time within one hour post-application</time_frame>
    <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</measure>
    <time_frame>Up to one hour post-application</time_frame>
    <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>No Disease State or Condition</condition>
  <arm_group>
    <arm_group_label>Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session. Used in Stage II of the study only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session. Used in Stage II of the study only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: One spray CTY-5339-A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: One spray CTY-5339-CB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: One spray CTY-5339-P</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>One spray CTY-5339-A</intervention_name>
    <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.</description>
    <arm_group_label>Stage I: One spray CTY-5339-A</arm_group_label>
    <arm_group_label>Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB</arm_group_label>
    <arm_group_label>Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A</arm_group_label>
    <other_name>CTY-5339-A</other_name>
    <other_name>CTY-5339 Anesthetic Spray</other_name>
    <other_name>benzocaine</other_name>
    <other_name>tetracaine</other_name>
    <other_name>tetracaine HCl</other_name>
    <other_name>14.0% benzocaine</other_name>
    <other_name>2.0% tetracaine HCl</other_name>
    <other_name>2.0% tetracaine</other_name>
    <other_name>14.0% benzocaine and 2.0% tetracaine HCl</other_name>
    <other_name>14.0% benzocaine and 2.0% tetracaine</other_name>
    <other_name>benzocaine and tetracaine HCl</other_name>
    <other_name>benzocaine and tetracaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>One spray CTY-5339-CB</intervention_name>
    <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.</description>
    <arm_group_label>Stage I: One spray CTY-5339-CB</arm_group_label>
    <arm_group_label>Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB</arm_group_label>
    <arm_group_label>Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A</arm_group_label>
    <other_name>CTY-5339-CB</other_name>
    <other_name>benzocaine</other_name>
    <other_name>14.0% benzocaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>One spray CTY-5339-P</intervention_name>
    <description>Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).</description>
    <arm_group_label>Stage I: One spray CTY-5339-P</arm_group_label>
    <other_name>CTY-5339-P</other_name>
    <other_name>placebo</other_name>
    <other_name>vehicle control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects between 18-75 years of age with a Body Mass Index (BMI) ≤32;&#xD;
&#xD;
          -  Subjects are category I or II on the American Society of Anesthesiologists physical&#xD;
             status classification system (ASA category I or II) and are in normal physical health&#xD;
             as judged by physical and laboratory examinations;&#xD;
&#xD;
          -  Subjects have normal appearance of the oral mucosal tissues;&#xD;
&#xD;
          -  At screening and at Baseline during Stage 1 and Sessions 1 and 2, of Stage 2 subjects&#xD;
             with Pin-Prick-Test (PPT) scores of at least &quot;3&quot; (on a 10 point numerical rating scale&#xD;
             [NRS]) on the 2 readings, 1 of which must be a score of at least &quot;4&quot;;&#xD;
&#xD;
          -  Subjects have mean quantitative sensory test of heat (QST-Heat) pain sensation&#xD;
             temperature assessments on the gingival mucosa of 46.5 °C or less based on the average&#xD;
             of the 2 readings at screening and at the Baseline Study Sessions for Stages 1 and 2;&#xD;
&#xD;
          -  Subjects must agree to refrain from ingesting any systemic or topical analgesic&#xD;
             medication for 3 days or 5 half-lives of the drug prior to and during the study period&#xD;
             and alcohol for 1 day prior to and during the study period;&#xD;
&#xD;
          -  Subjects must agree to refrain from using mouth rinses, cough drops or throat lozenges&#xD;
             on the day of each test session;&#xD;
&#xD;
          -  Female subjects must be physically incapable of childbearing potential (postmenopausal&#xD;
             for more than 1 year or surgically sterile) or practicing an acceptable method of&#xD;
             contraception (hormonal, barrier with spermicide, intrauterine device, vasectomized or&#xD;
             same sex partner, or abstinence). Subjects using hormonal birth control must have been&#xD;
             on a stable dose of treatment for at least 30 days and received at least 1 cycle of&#xD;
             treatment prior to randomization. At Screening and at Baseline of both sessions, all&#xD;
             females of childbearing potential must have a negative urine pregnancy test and not be&#xD;
             breastfeeding;&#xD;
&#xD;
          -  Negative urine drug screen for drugs of abuse at Screening and at Baseline for each&#xD;
             Study Session. A positive drug screen result may be permitted if the subject has been&#xD;
             on a stable dose of an allowed medication for &gt;30 days;&#xD;
&#xD;
          -  Subjects must be capable of reading, comprehending, and signing the informed consent&#xD;
             form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of any significant hepatic, renal, endocrine, cardiac,&#xD;
             neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic&#xD;
             disorders, including glaucoma, diabetes, emphysema, and chronic bronchitis;&#xD;
&#xD;
          -  Subjects with a history of any type of cancer other than skin related cancers;&#xD;
&#xD;
          -  Subjects with conditions that affect the absorption, metabolism, or passage of drugs&#xD;
             out of the body, (e.g., sprue, celiac disease, Crohn's disease, colitis, or liver,&#xD;
             kidney, or thyroid conditions);&#xD;
&#xD;
          -  Subjects with any history of alcohol or substance abuse (including a positive drug&#xD;
             screen test);&#xD;
&#xD;
          -  Subjects that currently have or have a history of uncontrolled hypertension;&#xD;
&#xD;
          -  Subjects with a known hypersensitivity to any local anesthetic drug;&#xD;
&#xD;
          -  Subjects with a hematocrit level significantly below the normal range on the screening&#xD;
             laboratory examination (as judged by the PI);&#xD;
&#xD;
          -  Subjects with any clinically significant abnormal lab result (as judged by the PI);&#xD;
&#xD;
          -  Subjects with any condition or history felt by the Investigator to place the subject&#xD;
             at increased risk;&#xD;
&#xD;
          -  Subjects who have smoked or chewed tobacco-containing substances within 6 months prior&#xD;
             to the start of the study;&#xD;
&#xD;
          -  Subjects judged by the Investigator to be unable or unwilling to comply with the&#xD;
             requirements of the protocol;&#xD;
&#xD;
          -  Subjects who have used an investigational drug within 30 days prior to entering the&#xD;
             study;&#xD;
&#xD;
          -  Subjects who have donated blood within 3 months prior to the start of the study;&#xD;
&#xD;
          -  Subjects who have previously participated in the trial;&#xD;
&#xD;
          -  Subjects who are members of the study site staff directly involved with the study or a&#xD;
             relative of the Sponsor or other personnel involved with the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen A Cooper, DMD, PhD</last_name>
    <role>Study Chair</role>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania, School of Dental Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <results_first_submitted>June 5, 2019</results_first_submitted>
  <results_first_submitted_qc>August 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2019</results_first_posted>
  <last_update_submitted>August 20, 2019</last_update_submitted>
  <last_update_submitted_qc>August 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>local anesthesia</keyword>
  <keyword>pain tolerance</keyword>
  <keyword>experimental pain</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
    <mesh_term>Tetracaine</mesh_term>
    <mesh_term>Benzocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 24, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03233737/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Stage I: One Spray CTY-5339-A</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="P2">
          <title>Stage I: One Spray CTY-5339-CB</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="P3">
          <title>Stage I: One Spray CTY-5339-P</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="P4">
          <title>Stage II: One Spray CTY-5339-A, Then One Spray CTY-5339-CB</title>
          <description>A single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session. Used in Stage II of the study only.</description>
        </group>
        <group group_id="P5">
          <title>Stage II: One Spray of CTY-5339-CB, Then One Spray CTY-5339-A</title>
          <description>A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session. Used in Stage II of the study only.</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="5"/>
                <participants group_id="P4" count="24"/>
                <participants group_id="P5" count="26"/>
              </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="5"/>
                <participants group_id="P4" count="24"/>
                <participants group_id="P5" count="26"/>
              </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 group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Stage II: One Spray CTY-5339-A, Then One Spray CTY-5339-CB</title>
          <description>A single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session. Used in Stage II of the study only.</description>
        </group>
        <group group_id="B2">
          <title>Stage II: One Spray of CTY-5339-CB, Then One Spray CTY-5339-A</title>
          <description>A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session. Used in Stage II of the study only.</description>
        </group>
        <group group_id="B3">
          <title>Stage I: One Spray CTY-5339-A</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="B4">
          <title>Stage I: One Spray CTY-5339-CB</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="B5">
          <title>Stage I: One Spray CTY-5339-P</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
        </group>
        <group group_id="B6">
          <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="24"/>
            <count group_id="B2" value="26"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="10"/>
            <count group_id="B5" value="5"/>
            <count group_id="B6" value="75"/>
          </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="24.3" spread="4.9"/>
                    <measurement group_id="B2" value="23.5" spread="1.8"/>
                    <measurement group_id="B3" value="28.1" spread="6.0"/>
                    <measurement group_id="B4" value="27.6" spread="2.5"/>
                    <measurement group_id="B5" value="26.2" spread="2.4"/>
                    <measurement group_id="B6" value="25.1" spread="3.9"/>
                  </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="15"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="26"/>
                  </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="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="67"/>
                  </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 group_id="B5" value="0"/>
                    <measurement group_id="B6" 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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="30"/>
                  </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 group_id="B5" value="0"/>
                    <measurement group_id="B6" 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="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="38"/>
                  </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 group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="5"/>
                  </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="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (lbs)</title>
          <units>lbs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="154.1" spread="33.0"/>
                    <measurement group_id="B2" value="141.2" spread="27.6"/>
                    <measurement group_id="B3" value="151.6" spread="31.0"/>
                    <measurement group_id="B4" value="128.1" spread="22.5"/>
                    <measurement group_id="B5" value="166.0" spread="35.4"/>
                    <measurement group_id="B6" value="146.6" spread="29.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height (inches)</title>
          <units>inches</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67.3" spread="4.1"/>
                    <measurement group_id="B2" value="65.8" spread="2.6"/>
                    <measurement group_id="B3" value="66.9" spread="4.2"/>
                    <measurement group_id="B4" value="65.1" spread="1.9"/>
                    <measurement group_id="B5" value="67.2" spread="2.3"/>
                    <measurement group_id="B6" value="66.4" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Stage II: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</title>
        <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</title>
          <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.6" spread="16.1"/>
                    <measurement group_id="O2" value="7.4" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Stage II: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</title>
        <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB</title>
          <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.5" spread="13.6"/>
                    <measurement group_id="O2" value="40.8" spread="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Stage I: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</title>
        <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <population>Placebo duration of effect was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</title>
          <description>The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (&lt; 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
          <population>Placebo duration of effect was not analyzed.</population>
          <units>minutes</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.2" spread="14.34"/>
                    <measurement group_id="O2" value="21.3" spread="15.47"/>
                    <measurement group_id="O3" value="25.2" spread="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Stage I: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</title>
        <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)</title>
          <description>The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based &quot;Duration of effect&quot; was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (&lt;3 °C) than Baseline indicated regression or absence of analgesia. Stage I outcome.</description>
          <units>minutes</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.5" spread="21.10"/>
                    <measurement group_id="O2" value="6.1" spread="11.49"/>
                    <measurement group_id="O3" value="5" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Onset of Anesthesia for Pin Prick Test (PPT)</title>
        <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Onset of Anesthesia for Pin Prick Test (PPT)</title>
          <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="0.2"/>
                    <measurement group_id="O2" value="1.1" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</title>
        <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</title>
          <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="1.4"/>
                    <measurement group_id="O2" value="1.3" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</title>
        <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</title>
          <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responded to treatment at the 1 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 2 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 3 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 4 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 5 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 10 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 15 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 20 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 25 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                    <measurement group_id="O2" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 35 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 40 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 45 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 50 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 55 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</title>
        <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</title>
          <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responded to treatment at the 1 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 2 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 3 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 4 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 5 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 10 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 15 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 20 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 25 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 35 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 40 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 45 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 50 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 55 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
        <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Any time within one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
          <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
        <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
          <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage II outcome.</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.6" spread="16.1"/>
                    <measurement group_id="O2" value="7.4" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</title>
        <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage II outcome.</description>
        <time_frame>Any time within one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</title>
          <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage II outcome.</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="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</title>
        <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</title>
          <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
          <units>score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SPID at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-85.2" spread="35.9"/>
                    <measurement group_id="O2" value="-63.2" spread="29.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPID at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-122.6" spread="63.52"/>
                    <measurement group_id="O2" value="-86.6" spread="53.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</title>
        <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
          <group group_id="O2">
            <title>One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</title>
          <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage II outcome.</description>
          <units>Degrees Celcius (ºC)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>STID at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="136.5" spread="67.78"/>
                    <measurement group_id="O2" value="96.6" spread="72.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>STID at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="214" spread="140.10"/>
                    <measurement group_id="O2" value="149.1" spread="142.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</title>
        <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Time of application up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-A: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-CB: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point</title>
          <description>Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responded to treatment at the 1 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 2 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 3 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 4 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 5 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 10 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 15 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 20 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 25 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 35 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 40 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 45 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 50 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 55 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</title>
        <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Time of application up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-A: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-CB: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point</title>
          <description>Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responded to treatment at the 1 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 2 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 3 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 4 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 5 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 10 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 15 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 20 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 25 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 35 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 40 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 45 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 50 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 55 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responded to treatment at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <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>Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
        <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-A: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-CB: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.&#xD;
One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
          <description>Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
          <units>minutes</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.5" spread="11.7"/>
                    <measurement group_id="O2" value="2.9" spread="3.3"/>
                    <measurement group_id="O3" value="0.2" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</title>
        <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage I outcome.</description>
        <time_frame>Any time within one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)</title>
          <description>QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.&#xD;
Stage I outcome.</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <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>Stage I: Onset of Anesthesia for Pin Prick Test (PPT)</title>
        <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Onset of Anesthesia for Pin Prick Test (PPT)</title>
          <description>Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
          <units>minutes</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="0.7"/>
                    <measurement group_id="O2" value="1.2" spread="0.4"/>
                    <measurement group_id="O3" value="2.8" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</title>
        <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)</title>
          <description>Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.&#xD;
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.&#xD;
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.&#xD;
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
          <units>minutes</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="2.9"/>
                    <measurement group_id="O2" value="0.4" spread="0.7"/>
                    <measurement group_id="O3" value="0.8" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
        <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
        <time_frame>Any time within one hour post-application</time_frame>
        <population>Placebo percentage of response was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)</title>
          <description>Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
Stage I outcome.</description>
          <population>Placebo percentage of response was not analyzed.</population>
          <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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</title>
        <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)</title>
          <description>SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
          <units>score</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SPID at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-82.1" spread="34.9"/>
                    <measurement group_id="O2" value="-37.8" spread="42.3"/>
                    <measurement group_id="O3" value="-29.3" spread="36.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPID at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-128.1" spread="76.6"/>
                    <measurement group_id="O2" value="-44.0" spread="52.7"/>
                    <measurement group_id="O3" value="-53.3" spread="69.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</title>
        <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
        <time_frame>Up to one hour post-application</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Stage I: One Spray CTY-5339-A</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O2">
            <title>Stage I: One Spray CTY-5339-CB</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
          <group group_id="O3">
            <title>Stage I: One Spray CTY-5339-P</title>
            <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.</description>
          </group>
        </group_list>
        <measure>
          <title>Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)</title>
          <description>STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.&#xD;
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).&#xD;
Stage I outcome.</description>
          <units>Degrees Celcius (ºC)</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>STID at the 30 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153.0" spread="72.0"/>
                    <measurement group_id="O2" value="10.4" spread="89.4"/>
                    <measurement group_id="O3" value="72.5" spread="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>STID at the 60 minute time point</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="320.2" spread="167.2"/>
                    <measurement group_id="O2" value="26.1" spread="137.0"/>
                    <measurement group_id="O3" value="134.6" spread="94.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data collected during and for one hour post testing.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>One Spray CTY-5339-A</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
        </group>
        <group group_id="E2">
          <title>One Spray CTY-5339-CB</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
        </group>
        <group group_id="E3">
          <title>One Spray CTY-5339-P</title>
          <description>Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Non-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="2" subjects_at_risk="60"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="60"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <description>Mild Headache</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <description>Mild Nasal Congestion</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <description>Mild Oropharyngeal pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <description>Moderate case of streptococcal pharyngitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <description>Mild Pruritus</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <description>Mild Rash</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </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>Elliot V Hersh, DMD, Ph.D., Director Clinical Pharmacology Research</name_or_title>
      <organization>University of Pennsylvania, School of Dental Medicine</organization>
      <phone>215-898-9686</phone>
      <email>evhersh@pobox.upenn.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/NCT03233737
org study id: C-003
nct id: NCT03233737
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine if the topical application to gingival tissue of
      the combination of benzocaine and tetracaine has a longer duration of local anesthetic
      activity than benzocaine alone.
In a blinded study, either benzocaine alone or the combination of benzocaine and tetracaine
      will be sprayed onto the gingival mucosal tissue. Onset and duration of local anesthesia will
      be evaluated over a one hour period using pin prick and quantitative sensory testing of heat
      (QST-heat) stimulation. Subjects will receive both treatments in a cross-over design with
      each session separated by 4-14 days. A total of 50 subjects (normal volunteers) will be
      evaluated.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: Stage II: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
time frame: Up to one hour post-application
description: The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (< 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
time frame: Up to one hour post-application
description: The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based "Duration of effect" was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (<3 °C) than Baseline indicated regression or absence of analgesia. Stage
measure: Stage I: Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)
time frame: Up to one hour post-application
description: The duration of effect, was defined as the length of time in minutes from onset of anesthesia to the absence of anesthesia.Onset was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than Baseline. Absence of anesthesia was defined as follows: After Onset had been established, absence was the first of two time points with consecutive occurrences of regression of absence of analgesia. Reports of less pain by ≥1 unit than Baseline indicated analgesia; while a report of similar (< 1 unit) or more pain than Baseline indicated regression or absence of analgesia. The minimum onset time was 1 minute. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB Compared to One Spray CTY-5339-P (Placebo: Vehicle Control)
time frame: Up to one hour post-application
description: The duration of effect, was defined as the time from onset to treatment failure, as measured by QST Heat score. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. The QST Heat-based "Duration of effect" was calculated by the length of time in minutes from onset of anesthesia to the absence of anesthesia where Onset of anesthesia was defined by PPT unless specific QST thresholds were not met. After Onset had been established, absence of analgesia or offset was the first of two time points with consecutive occurrences of regression or absence of analgesia. Reports of QST heat pain temperature by ≥ 3 °C of the Baseline QST indicated analgesia; while a report of similar (<3 °C) than Baseline indicated regression or absence of analgesia. Stage I outcome.
measure: Stage II: Onset of Anesthesia for Pin Prick Test (PPT)
time frame: Up to one hour post-application
description: Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
time frame: Up to one hour post-application
description: Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
time frame: Up to one hour post-application
description: Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
time frame: Up to one hour post-application
description: Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST.
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
time frame: Any time within one hour post-application
description: Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
time frame: Up to one hour post-application
description: Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage II outcome.
measure: Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
time frame: Any time within one hour post-application
description: QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.
Stage II outcome.
measure: Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
time frame: Up to one hour post-application
description: SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).
Stage II outcome.
measure: Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
time frame: Up to one hour post-application
description: STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).
Stage II outcome.
measure: Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
time frame: Time of application up to one hour post-application
description: Response at at time point is defined as when the PPT average pain score was less than the Baseline PPT average score by any amount. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
time frame: Time of application up to one hour post-application
description: Response at a time point is defined as an increase of QST heat pain temperature by ≥ 3 degrees C compared to the Baseline QST. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
time frame: Up to one hour post-application
description: Response at a time point is defined as having the PPT average pain score of ≤2. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
time frame: Any time within one hour post-application
description: QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point. Reaching maximum heat for QST Heat was defined as subjects reaching the maximum temperature without reporting pain at one or more time points.
Stage I outcome.
measure: Stage I: Onset of Anesthesia for Pin Prick Test (PPT)
time frame: Up to one hour post-application
description: Onset of anesthesia was the time point at which the PPT average pain score was less than the Baseline PPT average score by any amount. Also, in 10 minutes or less, the subject must have had a lower PPT average pain score of ≥ 1 unit than the Baseline PPT. Onset was expected to be between 1 and 5 minutes. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
time frame: Up to one hour post-application
description: Onset of anesthesia was defined by Pin Prick Test (PPT) unless specific QST thresholds were not met.
If the PPT Onset was 5 minutes or less, then QST must have been greater than the Baseline QST temperature at 5 minutes by any amount and QST must have been ≥ 3 °C of the Baseline QST at 5 or 10 minutes.
If the PPT Onset was 10 minutes, then QST must have been ≥ 3 °C of the Baseline QST temperature at 10 minutes.
If PPT did not achieve Onset, then QST alone could have achieved onset at either 5 or 10 minutes if QST was greater than the Baseline QST temperature at 5 or 10 minutes by any amount and the QST was ≥ 3 °C of the Baseline QST at 5 or 10 minutes.
QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
time frame: Any time within one hour post-application
description: Response is defined as a subject having a PPT average pain score of ≤2 recorded at any single time point where PPT was performed. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
Stage I outcome.
measure: Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
time frame: Up to one hour post-application
description: SPID was calculated as a sum of the delta PPT scores at each time point until the designated time point. The delta PPT score is defined as the change in PPT score from baseline. PPT scores were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
The total possible scale range was from -100 (best) to +100 (worst) for SPID at the 30 minute time point, and from -160 (best) to +160 (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).
Stage I outcome.
measure: Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
time frame: Up to one hour post-application
description: STID was calculated as a sum of the delta QST Heat scores at each time point until the designated time point. The delta QST Heat score is defined as the change in QST Heat score from baseline. QST Heat scores were the temperature where the sensation of a heat stimuli was felt: ranging from 35 ºC to a maximum of 50.5 ºC with intervals of 0.5 ºC, at a frequency of every 1 minute for the first 5 minutes and then every 5 minutes thereafter until the final 60 minute time point.
The total possible scale range was from -155 ºC (best) to +155 ºC (worst) for STID at the 30 minute time point, and from -248 ºC (best) to +248 ºC (worst) for SPID at the 60 minute time point Lower scores signify a better outcome (less sensitive to pain than at baseline = less pain with therapy = therapy was more effective).
Stage I outcome.
arm group label: Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB
arm group type: Experimental
description: A single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session. Used in Stage II of the study only.
arm group label: Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A
arm group type: Active Comparator
description: A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a single spray of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session. Used in Stage II of the study only.
arm group label: Stage I: One spray CTY-5339-A
arm group type: Experimental
description: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.
arm group label: Stage I: One spray CTY-5339-CB
arm group type: Active Comparator
description: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.
arm group label: Stage I: One spray CTY-5339-P
arm group type: Placebo Comparator
description: Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (placebo: vehicle control). Administered in a single anesthetic spray. Tested over a 60 minute session. Used in Stage I of the study only.
intervention type: Combination Product
intervention name: One spray CTY-5339-A
description: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 28 mg) and 2.0% Tetracaine Hydrochloride (USP = 4 mg). Administered in a single anesthetic spray.
arm group label: Stage I: One spray CTY-5339-A
arm group label: Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB
arm group label: Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A
other name: CTY-5339-A
other name: CTY-5339 Anesthetic Spray
other name: benzocaine
other name: tetracaine
other name: tetracaine HCl
other name: 14.0% benzocaine
other name: 2.0% tetracaine HCl
other name: 2.0% tetracaine
other name: 14.0% benzocaine and 2.0% tetracaine HCl
other name: 14.0% benzocaine and 2.0% tetracaine
other name: benzocaine and tetracaine HCl
other name: benzocaine and tetracaine
intervention type: Device
intervention name: One spray CTY-5339-CB
description: Metered spray bottle with ≈200 uL total spray volume. Contains the active ingredient: 14.0% Benzocaine (USP = 28 mg). Administered in a single anesthetic spray.
arm group label: Stage I: One spray CTY-5339-CB
arm group label: Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB
arm group label: Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A
other name: CTY-5339-CB
other name: benzocaine
other name: 14.0% benzocaine
intervention type: Device
intervention name: One spray CTY-5339-P
description: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).
arm group label: Stage I: One spray CTY-5339-P
other name: CTY-5339-P
other name: placebo
other name: vehicle control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen A Cooper, DMD, PhD
role: Study Chair
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anesthetics
mesh term: Tetracaine
mesh term: Benzocaine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 