Pain Study to Assess Local Anesthetic Efficacy and Safety of CTY-5339 on Gingival Mucosal Tissue in Normal Volunteers

• Sponsor: Cetylite Industries (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03233737
• Collaborator: (none)
• Enrollment: 75
• Location: 1
• Arms: 5
• Actual Duration (Months): 8.2
• Patients Per Site Per Month: 9.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
No Disease State or Condition	Combination Product: One spray CTY-5339-A; Device: One spray CTY-5339-CB; Device: One spray CTY-5339-P	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Jun 15, 2017
• Actual Primary Completion Date: Feb 20, 2018
• Actual Study Completion Date: Feb 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stage II: One spray CTY-5339-A, then one spray CTY-5339-CB 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.	Combination Product: 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.; Other Names: CTY-5339-A CTY-5339 Anesthetic Spray benzocaine tetracaine tetracaine HCl 14.0% benzocaine 2.0% tetracaine HCl 2.0% tetracaine 14.0% benzocaine and 2.0% tetracaine HCl 14.0% benzocaine and 2.0% tetracaine benzocaine and tetracaine HCl benzocaine and tetracaine ; Device: 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.; Other Names: CTY-5339-CB benzocaine 14.0% benzocaine
Active Comparator: Stage II: One spray of CTY-5339-CB, then one spray CTY-5339-A 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.	Combination Product: 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.; Other Names: CTY-5339-A CTY-5339 Anesthetic Spray benzocaine tetracaine tetracaine HCl 14.0% benzocaine 2.0% tetracaine HCl 2.0% tetracaine 14.0% benzocaine and 2.0% tetracaine HCl 14.0% benzocaine and 2.0% tetracaine benzocaine and tetracaine HCl benzocaine and tetracaine ; Device: 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.; Other Names: CTY-5339-CB benzocaine 14.0% benzocaine
Experimental: Stage I: 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. Tested over a 60 minute session. Used in Stage I of the study only.	Combination Product: 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.; Other Names: CTY-5339-A CTY-5339 Anesthetic Spray benzocaine tetracaine tetracaine HCl 14.0% benzocaine 2.0% tetracaine HCl 2.0% tetracaine 14.0% benzocaine and 2.0% tetracaine HCl 14.0% benzocaine and 2.0% tetracaine benzocaine and tetracaine HCl benzocaine and tetracaine
Active Comparator: Stage I: 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. Tested over a 60 minute session. Used in Stage I of the study only.	Device: 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.; Other Names: CTY-5339-CB benzocaine 14.0% benzocaine
Placebo Comparator: Stage I: One spray CTY-5339-P 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.	Device: One spray CTY-5339-P; Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).; Other Names: CTY-5339-P placebo vehicle control

Outcome Measures

Primary Outcome Measures

1. 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 [Up to one hour post-application]

   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.

2. 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 [Up to one hour post-application]

   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

3. 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) [Up to one hour post-application]

   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.

4. 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) [Up to one hour post-application]

   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.

Secondary Outcome Measures

1. Stage II: Onset of Anesthesia for Pin Prick Test (PPT) [Up to one hour post-application]

   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.

2. Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat) [Up to one hour post-application]

   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.

3. Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point [Up to one hour post-application]

   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.

4. Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point [Up to one hour post-application]

   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.

5. Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale) [Any time within one hour post-application]

   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.

6. Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale) [Up to one hour post-application]

   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.

7. Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat) [Any time within one hour post-application]

   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.

8. Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc) [Up to one hour post-application]

   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.

9. Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc) [Up to one hour post-application]

   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.

10. Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point [Time of application up to one hour post-application]

    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.

11. Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point [Time of application up to one hour post-application]

    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.

12. Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale) [Up to one hour post-application]

    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.

13. Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat) [Any time within one hour post-application]

    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.

14. Stage I: Onset of Anesthesia for Pin Prick Test (PPT) [Up to one hour post-application]

    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.

15. Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat) [Up to one hour post-application]

    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.

16. Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale) [Any time within one hour post-application]

    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.

17. Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc) [Up to one hour post-application]

    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.

18. Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc) [Up to one hour post-application]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male and female subjects between 18-75 years of age with a Body Mass Index (BMI) ≤32;

• Subjects are category I or II on the American Society of Anesthesiologists physical status classification system (ASA category I or II) and are in normal physical health as judged by physical and laboratory examinations;

• Subjects have normal appearance of the oral mucosal tissues;

• At screening and at Baseline during Stage 1 and Sessions 1 and 2, of Stage 2 subjects with Pin-Prick-Test (PPT) scores of at least "3" (on a 10 point numerical rating scale [NRS]) on the 2 readings, 1 of which must be a score of at least "4";

• Subjects have mean quantitative sensory test of heat (QST-Heat) pain sensation temperature assessments on the gingival mucosa of 46.5 °C or less based on the average of the 2 readings at screening and at the Baseline Study Sessions for Stages 1 and 2;

• Subjects must agree to refrain from ingesting any systemic or topical analgesic medication for 3 days or 5 half-lives of the drug prior to and during the study period and alcohol for 1 day prior to and during the study period;

• Subjects must agree to refrain from using mouth rinses, cough drops or throat lozenges on the day of each test session;

• Female subjects must be physically incapable of childbearing potential (postmenopausal for more than 1 year or surgically sterile) or practicing an acceptable method of contraception (hormonal, barrier with spermicide, intrauterine device, vasectomized or same sex partner, or abstinence). Subjects using hormonal birth control must have been on a stable dose of treatment for at least 30 days and received at least 1 cycle of treatment prior to randomization. At Screening and at Baseline of both sessions, all females of childbearing potential must have a negative urine pregnancy test and not be breastfeeding;

• Negative urine drug screen for drugs of abuse at Screening and at Baseline for each Study Session. A positive drug screen result may be permitted if the subject has been on a stable dose of an allowed medication for >30 days;

• Subjects must be capable of reading, comprehending, and signing the informed consent form.

Exclusion Criteria:

• Subjects with a history of any significant hepatic, renal, endocrine, cardiac, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorders, including glaucoma, diabetes, emphysema, and chronic bronchitis;

• Subjects with a history of any type of cancer other than skin related cancers;

• Subjects with conditions that affect the absorption, metabolism, or passage of drugs out of the body, (e.g., sprue, celiac disease, Crohn's disease, colitis, or liver, kidney, or thyroid conditions);

• Subjects with any history of alcohol or substance abuse (including a positive drug screen test);

• Subjects that currently have or have a history of uncontrolled hypertension;

• Subjects with a known hypersensitivity to any local anesthetic drug;

• Subjects with a hematocrit level significantly below the normal range on the screening laboratory examination (as judged by the PI);

• Subjects with any clinically significant abnormal lab result (as judged by the PI);

• Subjects with any condition or history felt by the Investigator to place the subject at increased risk;

• Subjects who have smoked or chewed tobacco-containing substances within 6 months prior to the start of the study;

• Subjects judged by the Investigator to be unable or unwilling to comply with the requirements of the protocol;

• Subjects who have used an investigational drug within 30 days prior to entering the study;

• Subjects who have donated blood within 3 months prior to the start of the study;

• Subjects who have previously participated in the trial;

• Subjects who are members of the study site staff directly involved with the study or a relative of the Sponsor or other personnel involved with the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania, School of Dental Medicine	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Cetylite Industries

Investigators

• Study Chair: Stephen A Cooper, DMD, PhD,

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 24, 2017

More Information

Publications

None provided.

• Responsible Party: Cetylite Industries
• ClinicalTrials.gov Identifier: NCT03233737
• Other Study ID Numbers: C-003
• First Posted: Jul 31, 2017
• Last Update Posted: Aug 21, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cetylite Industries: local anesthesia; pain tolerance; experimental pain
• Additional relevant MeSH terms: Anesthetics; Tetracaine; Benzocaine

Study Results

Participant Flow

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P	Stage II: One Spray CTY-5339-A, Then One Spray CTY-5339-CB	Stage II: One Spray of CTY-5339-CB, Then One Spray CTY-5339-A
Arm/Group 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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	10	10	5	24	26
COMPLETED	10	10	5	24	26
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Stage II: One Spray CTY-5339-A, Then One Spray CTY-5339-CB	Stage II: One Spray of CTY-5339-CB, Then One Spray CTY-5339-A	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P	Total
Arm/Group 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.	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	24	26	10	10	5	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (4.9)	23.5 (1.8)	28.1 (6.0)	27.6 (2.5)	26.2 (2.4)	25.1 (3.9)
Sex: Female, Male (Count of Participants)
Female	15 62.5%	21 80.8%	4 40%	8 80%	1 20%	49 65.3%
Male	9 37.5%	5 19.2%	6 60%	2 20%	4 80%	26 34.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 11.5%	2 20%	1 10%	2 40%	8 10.7%
Not Hispanic or Latino	24 100%	23 88.5%	8 80%	9 90%	3 60%	67 89.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	8 33.3%	12 46.2%	4 40%	5 50%	1 20%	30 40%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 4.2%	0 0%	1 10%	0 0%	0 0%	2 2.7%
White	13 54.2%	12 46.2%	5 50%	5 50%	3 60%	38 50.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 8.3%	2 7.7%	0 0%	0 0%	1 20%	5 6.7%
Region of Enrollment (participants) [Number]
United States	24 100%	26 100%	10 100%	10 100%	5 100%	75 100%
Weight (lbs) (lbs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lbs]	154.1 (33.0)	141.2 (27.6)	151.6 (31.0)	128.1 (22.5)	166.0 (35.4)	146.6 (29.9)
Height (inches) (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	67.3 (4.1)	65.8 (2.6)	66.9 (4.2)	65.1 (1.9)	67.2 (2.3)	66.4 (3.3)

Outcome Measures

1. Primary Outcome

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
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Mean (Standard Deviation) [minutes]	14.6 (16.1)	7.4 (11.1)

2. Primary Outcome

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
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
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Mean (Standard Deviation) [minutes]	45.5 (13.6)	40.8 (16.3)

3. Primary Outcome

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)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

Placebo duration of effect was not analyzed.

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Mean (Standard Deviation) [minutes]	49.2 (14.34)	21.3 (15.47)	25.2 (30.9)

4. Primary Outcome

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)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Mean (Standard Deviation) [minutes]	42.5 (21.10)	6.1 (11.49)	5 (9.3)

5. Secondary Outcome

Title	Stage II: Onset of Anesthesia for Pin Prick Test (PPT)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Mean (Standard Deviation) [minutes]	1.1 (0.2)	1.1 (0.6)

6. Secondary Outcome

Title	Stage II: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Mean (Standard Deviation) [minutes]	1 (1.4)	1.3 (2.4)

7. Secondary Outcome

Title	Stage II: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Responded to treatment at the 1 minute time point	47 195.8%	46 176.9%
Responded to treatment at the 2 minute time point	50 208.3%	48 184.6%
Responded to treatment at the 3 minute time point	50 208.3%	48 184.6%
Responded to treatment at the 4 minute time point	49 204.2%	48 184.6%
Responded to treatment at the 5 minute time point	49 204.2%	49 188.5%
Responded to treatment at the 10 minute time point	49 204.2%	49 188.5%
Responded to treatment at the 15 minute time point	49 204.2%	48 184.6%
Responded to treatment at the 20 minute time point	49 204.2%	46 176.9%
Responded to treatment at the 25 minute time point	48 200%	45 173.1%
Responded to treatment at the 30 minute time point	46 191.7%	42 161.5%
Responded to treatment at the 35 minute time point	43 179.2%	34 130.8%
Responded to treatment at the 40 minute time point	36 150%	27 103.8%
Responded to treatment at the 45 minute time point	32 133.3%	21 80.8%
Responded to treatment at the 50 minute time point	25 104.2%	20 76.9%
Responded to treatment at the 55 minute time point	20 83.3%	20 76.9%
Responded to treatment at the 60 minute time point	19 79.2%	18 69.2%

8. Secondary Outcome

Title	Stage II: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Responded to treatment at the 1 minute time point	36 150%	29 111.5%
Responded to treatment at the 2 minute time point	37 154.2%	30 115.4%
Responded to treatment at the 3 minute time point	37 154.2%	30 115.4%
Responded to treatment at the 4 minute time point	37 154.2%	30 115.4%
Responded to treatment at the 5 minute time point	37 154.2%	31 119.2%
Responded to treatment at the 10 minute time point	38 158.3%	34 130.8%
Responded to treatment at the 15 minute time point	38 158.3%	31 119.2%
Responded to treatment at the 20 minute time point	36 150%	29 111.5%
Responded to treatment at the 25 minute time point	32 133.3%	24 92.3%
Responded to treatment at the 30 minute time point	28 116.7%	19 73.1%
Responded to treatment at the 35 minute time point	24 100%	15 57.7%
Responded to treatment at the 40 minute time point	22 91.7%	15 57.7%
Responded to treatment at the 45 minute time point	19 79.2%	12 46.2%
Responded to treatment at the 50 minute time point	17 70.8%	12 46.2%
Responded to treatment at the 55 minute time point	14 58.3%	11 42.3%
Responded to treatment at the 60 minute time point	13 54.2%	9 34.6%

9. Secondary Outcome

Title	Stage II: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
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.
Time Frame	Any time within one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Count of Participants [Participants]	50 208.3%	50 192.3%

10. Secondary Outcome

Title	Stage II: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Mean (Standard Deviation) [minutes]	14.6 (16.1)	7.4 (11.1)

11. Secondary Outcome

Title	Stage II: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
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.
Time Frame	Any time within one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
Count of Participants [Participants]	7 29.2%	5 19.2%

12. Secondary Outcome

Title	Stage II: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
SPID at the 30 minute time point	-85.2 (35.9)	-63.2 (29.38)
SPID at the 60 minute time point	-122.6 (63.52)	-86.6 (53.15)

13. Secondary Outcome

Title	Stage II: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One Spray CTY-5339-A	One Spray CTY-5339-CB
Arm/Group 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.	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.
Measure Participants	50	50
STID at the 30 minute time point	136.5 (67.78)	96.6 (72.63)
STID at the 60 minute time point	214 (140.10)	149.1 (142.36)

14. Secondary Outcome

Title	Stage I: Percentage of Responders for Pin Prick Test (PPT) at Each Time Point
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.
Time Frame	Time of application up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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. 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.	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. 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.	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. One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).
Measure Participants	10	10	5
Responded to treatment at the 1 minute time point	8 33.3%	8 30.8%	4 40%
Responded to treatment at the 2 minute time point	9 37.5%	10 38.5%	3 30%
Responded to treatment at the 3 minute time point	10 41.7%	10 38.5%	3 30%
Responded to treatment at the 4 minute time point	10 41.7%	10 38.5%	3 30%
Responded to treatment at the 5 minute time point	10 41.7%	10 38.5%	2 20%
Responded to treatment at the 10 minute time point	10 41.7%	10 38.5%	3 30%
Responded to treatment at the 15 minute time point	10 41.7%	8 30.8%	3 30%
Responded to treatment at the 20 minute time point	10 41.7%	4 15.4%	2 20%
Responded to treatment at the 25 minute time point	9 37.5%	4 15.4%	2 20%
Responded to treatment at the 30 minute time point	9 37.5%	2 7.7%	2 20%
Responded to treatment at the 35 minute time point	9 37.5%	2 7.7%	2 20%
Responded to treatment at the 40 minute time point	8 33.3%	1 3.8%	2 20%
Responded to treatment at the 45 minute time point	7 29.2%	1 3.8%	2 20%
Responded to treatment at the 50 minute time point	7 29.2%	1 3.8%	2 20%
Responded to treatment at the 55 minute time point	6 25%	1 3.8%	2 20%
Responded to treatment at the 60 minute time point	6 25%	1 3.8%	2 20%

15. Secondary Outcome

Title	Stage I: Percentage of Responders for Heat Sensation Threshold (QST Heat) at Each Time Point
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.
Time Frame	Time of application up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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. 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.	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. 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.	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. One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).
Measure Participants	10	10	5
Responded to treatment at the 1 minute time point	7 29.2%	2 7.7%	4 40%
Responded to treatment at the 2 minute time point	7 29.2%	3 11.5%	4 40%
Responded to treatment at the 3 minute time point	8 33.3%	3 11.5%	4 40%
Responded to treatment at the 4 minute time point	8 33.3%	3 11.5%	4 40%
Responded to treatment at the 5 minute time point	8 33.3%	3 11.5%	4 40%
Responded to treatment at the 10 minute time point	9 37.5%	3 11.5%	4 40%
Responded to treatment at the 15 minute time point	9 37.5%	2 7.7%	4 40%
Responded to treatment at the 20 minute time point	9 37.5%	2 7.7%	4 40%
Responded to treatment at the 25 minute time point	9 37.5%	1 3.8%	1 10%
Responded to treatment at the 30 minute time point	8 33.3%	1 3.8%	0 0%
Responded to treatment at the 35 minute time point	6 25%	1 3.8%	0 0%
Responded to treatment at the 40 minute time point	6 25%	0 0%	0 0%
Responded to treatment at the 45 minute time point	6 25%	0 0%	0 0%
Responded to treatment at the 50 minute time point	6 25%	0 0%	0 0%
Responded to treatment at the 55 minute time point	6 25%	0 0%	0 0%
Responded to treatment at the 60 minute time point	6 25%	0 0%	0 0%

16. Secondary Outcome

Title	Stage I: Duration of Minimal Pain for Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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. 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.	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. 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.	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. One spray CTY-5339-P: Placebo. Metered spray bottle with ≈200 uL total spray volume. Contains no active ingredient (vehicle control).
Measure Participants	10	10	5
Mean (Standard Deviation) [minutes]	14.5 (11.7)	2.9 (3.3)	0.2 (0.4)

17. Secondary Outcome

Title	Stage I: Percentage of Subjects Reaching Maximum Heat for Heat Sensation Threshold (QST Heat)
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.
Time Frame	Any time within one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Count of Participants [Participants]	5 20.8%	0 0%	0 0%

18. Secondary Outcome

Title	Stage I: Onset of Anesthesia for Pin Prick Test (PPT)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Mean (Standard Deviation) [minutes]	1.3 (0.7)	1.2 (0.4)	2.8 (4.0)

19. Secondary Outcome

Title	Stage I: Onset of Anesthesia for Heat Sensation Threshold (QST Heat)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Mean (Standard Deviation) [minutes]	2.0 (2.9)	0.4 (0.7)	0.8 (0.4)

20. Secondary Outcome

Title	Stage I: Percentage of Subjects Reaching Minimal Pain on Pin Prick Test (PPT) (≤2 on Numerical Rating Scale Pain Scale)
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.
Time Frame	Any time within one hour post-application

Outcome Measure Data

Analysis Population Description

Placebo percentage of response was not analyzed.

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
Count of Participants [Participants]	10 41.7%	9 34.6%	2 20%

21. Secondary Outcome

Title	Stage I: Sum of Pain Intensity Differences (SPID) for Pin Prick Test (PPT) (Post-hoc)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
SPID at the 30 minute time point	-82.1 (34.9)	-37.8 (42.3)	-29.3 (36.3)
SPID at the 60 minute time point	-128.1 (76.6)	-44.0 (52.7)	-53.3 (69.1)

22. Secondary Outcome

Title	Stage I: Sum of Temperature Differences (STID) for Heat Sensation Threshold (QST Heat) (Post-hoc)
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.
Time Frame	Up to one hour post-application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I: One Spray CTY-5339-A	Stage I: One Spray CTY-5339-CB	Stage I: One Spray CTY-5339-P
Arm/Group 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.	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.	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.
Measure Participants	10	10	5
STID at the 30 minute time point	153.0 (72.0)	10.4 (89.4)	72.5 (33.6)
STID at the 60 minute time point	320.2 (167.2)	26.1 (137.0)	134.6 (94.3)

Adverse Events

Time Frame	Adverse event data collected during and for one hour post testing.
Arm/Group Title	One Spray CTY-5339-A		One Spray CTY-5339-CB		One Spray CTY-5339-P
Arm/Group 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.		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.		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.
All Cause Mortality
	One Spray CTY-5339-A		One Spray CTY-5339-CB		One Spray CTY-5339-P
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/60 (0%)		0/5 (0%)
Serious Adverse Events
	One Spray CTY-5339-A		One Spray CTY-5339-CB		One Spray CTY-5339-P
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/60 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	One Spray CTY-5339-A		One Spray CTY-5339-CB		One Spray CTY-5339-P
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/60 (3.3%)		2/60 (3.3%)		0/5 (0%)
Nervous system disorders
Headache	1/60 (1.7%)	1	0/60 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	1/60 (1.7%)	1	0/60 (0%)	0	0/5 (0%)	0
Oropharyngeal pain	1/60 (1.7%)	1	0/60 (0%)	0	0/5 (0%)	0
Pharyngitis streptococcal	0/60 (0%)	0	1/60 (1.7%)	1	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/60 (0%)	0	1/60 (1.7%)	1	0/5 (0%)	0
Rash	0/60 (0%)	0	1/60 (1.7%)	1	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.