The purpose of this study is to determine if the topical application to cheek 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 of the combination of benzocaine and tetracaine will be sprayed onto the cheek mucosal tissue. Onset and duration of local anesthesia will be evaluated over a one hour period using pin prick and QST heat stimulation. Subjects will receive both treatments in a cross-over design with each session separated by 5-7 days. A total of 76 subjects (normal volunteers) will be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
40
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.
Metered spray bottle with ≈400 uL total spray volume. Contains the active ingredients: 14.0% Benzocaine (USP = 56 mg total) and 2.0% Tetracaine Hydrochloride (USP = 8 mg total). Administered in two anesthetic sprays.
University of Pennsylvania, School of Dental Medicine Department of Oral & Maxillofacial Surgery
Philadelphia, Pennsylvania, United States
Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
Evaluations were completed at 1-minute intervals for the first 5 minutes to capture onset of anesthesia. Starting at 5 minutes after drug administration, the PPT was done at 5 minute intervals up to the one hour time point. If there was no indication of anesthesia by 10 minutes, the subject was considered a treatment failure and the assessment of PPT was discontinued. In addition, once onset of anesthesia had occurred, if there was no longer any anesthesia at two consecutive evaluation time points from 10 minutes onward, the assessment of PPT was discontinued. The PPT was assessed using a 90-mm, 26-gauge pencil-point spinal needle. At screening, 3 pin pricks were performed on each cheek. Pin pricks were assessed using a 0 (no pain) to 10 (severe pain) Numerical Rating Scale (NRS). In order to be eligible for the study, for each cheek, subjects must have had a minimum score of "3" for the last 2 pin pricks, and one of those scores had to be "4" or higher.
Time frame: Change in pain assessment from baseline (time of application) up to one hour post-application
Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB
Starting at 5 minutes after drug administration, the QST was done at 5 minute intervals up to the one hour time point. If there was no indication of anesthesia by 10 minutes, the subject was considered a treatment failure and the assessment of PPT was discontinued. In addition, once onset of anesthesia had occurred, if there was no longer any anesthesia at two consecutive evaluation time points from 10 minutes onward, the assessment of QST was discontinued. The heat stimuli were delivered in 3 repetitions, with inter-stimulus intervals of 30s. The basal thermode temperature was set at a comfortable 35ºC. The rate at which the thermode heated up was set at 0.5ºC/s, while the rate at which it cooled down was set at 8ºC/s. The maximum thermode temperature was set at 51ºC. Heat sensation threshold was defined as the temperature at which the subjects first felt tingling, warmth, heat, or pain.
Time frame: Change in temperature from baseline (time of application) up to one hour post-application
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A single spray of CTY-5339-CB in a metered spray bottle with ≈200 uL total spray volume, containing the active ingredient: 14.0% Benzocaine (USP = 28 mg). This was administered in combination with a single spray of CTY-5339-P (acting as vehicle control placebo with no active ingredient) in a metered spray bottle with ≈200 uL total spray volume. This combination was used to maintain double-blind conditions. The vehicle control was sprayed outside the circumscribed area to avoid dilution of active drug.
Duration of Anesthesia as Measured by Pin Prick Test (PPT) for Two Sprays CTY-5339-A Compared to One Spray CTY-5339-CB in Combination With One Spray CTY-5339-P (Placebo)
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that. Duration of effect was defined as the time (in minutes) from onset to treatment failure (i.e., for PPT, an assessment of "Same/More" pain, and for QST, the average heat temperature was greater than the average heat temperature at Baseline (non-treated cheek), up to the 60-minute time point (at two consecutive time points).
Time frame: Time of application up to one hour post-application
Duration of Anesthesia as Measured by QST Heat for Two Sprays CTY-5339-A Compared to One Spray CTY-5339-CB in Combination With One Spray CTY-5339-P (Placebo)
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that. Duration of effect was defined as the time (in minutes) from onset to treatment failure (i.e., for PPT, an assessment of "Same/More" pain, and for QST, the average heat temperature was greater than the average heat temperature at Baseline (non-treated cheek), up to the 60-minute time point (at two consecutive time points).
Time frame: Time of application up to one hour post-application
Duration of Anesthesia as Measured by PPT for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application
Duration of Anesthesia as Measured by QST Heat for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application
Onset of Anesthesia for PPT
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application
Onset of Anesthesia for QST Heat
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application
Percentage of Responders for PPT at Each Time Point
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application
Percentage of Responders for QST Heat at Each Time Point
Assessments will be made over a period of one hour, with assessments at 1 minute intervals for the first 5 minutes and then every 5 minutes after that.
Time frame: Time of application up to one hour post-application