Experimental Pain Study to Assess Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray in Normal Volunteers

A Double-blind, Partial Cross-over, Incomplete Factorial Study to Assess the Local Anesthetic Efficacy and Safety of CTY-5339 Anesthetic Spray (CTY-5339-A) When Applied to the Cheek Mucosal Tissue in Normal Volunteers

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02908620

Enrollment

Registered

2016-09-21

Start date

2016-12-07

Completion date

2017-06-07

Last updated

2019-07-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia

Brief summary

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.

Detailed description

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.

Interventions

COMBINATION_PRODUCTOne 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.

DRUGOne 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.

COMBINATION_PRODUCTTwo sprays CTY-5339-A

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.

DRUGOne spray CTY-5339-CB in combination with one spray CTY-5339-P (vehicle control: placebo)

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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Caregiver)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

* Male and female subjects between 18-75 years of age with a Body Mass Index (BMI) ≤32; * Subjects are ASA Category I or II and are in normal physical health as judged by physical and laboratory examinations; * Subjects with normal appearance of the oral mucosal tissues; * 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; * The subject is 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.

Design outcomes

Primary

Measure	Time frame	Description
Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	Change in pain assessment from baseline (time of application) up to one hour post-application	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.
Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	Change in temperature from baseline (time of application) up to one hour post-application	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.

Secondary

Measure	Time frame	Description
Duration of Anesthesia as Measured by PPT for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A	Time of application up to one hour post-application	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 Anesthesia as Measured by QST Heat for One Spray CTY-5339-A Compared to Two Sprays CTY-5339-A	Time of application up to one hour post-application	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.
Onset of Anesthesia for PPT	Time of application up to one hour post-application	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 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)	Time of application up to one hour post-application	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).
Percentage of Responders for PPT at Each Time Point	Time of application up to one hour post-application	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.
Percentage of Responders for QST Heat at Each Time Point	Time of application up to one hour post-application	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.
Onset of Anesthesia for QST Heat	Time of application up to one hour post-application	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 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)	Time of application up to one hour post-application	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).

Countries

United States

Participant flow

Recruitment details

Study conducted at the University of Pennsylvania School of Dental Medicine. 240 South 40th Street, Robert Schattner Center, Philadelphia, PA 19104. Recruitment was from normal volunteers.

Participants by arm

Arm	Count
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.	10
2 Sprays CTY-5339-A, Then 1 Spray CTY-5339-CB +1 Spray Placebo Two sprays 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) and a single spray of vehicle control (CTY-5339-P) (sprayed outside the circumscribed area to avoid dilution of active drug) tested over a 60 minute session.	10
One Spray of CTY-5339-CB, Then One Spray CTY-5339-A Two sprays 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) and a single spray of vehicle control (CTY-5339-P) (sprayed outside the circumscribed area to avoid dilution of active drug) tested over a 60 minute session.	10
1 Spray CTY-5339-CB +1 Spray Placebo, Then 2 Sprays CTY-5339-A A single spray of CTY-5339-CB Anesthetic Spray (14.0% benzocaine) and a single spray of vehicle control (CTY-5339-P) (sprayed outside the circumscribed area to avoid dilution of active drug) tested over a 60 minute session, followed by a 4-14 day washout period, followed by a two sprays of CTY-5339-A Anesthetic Spray (14.0% benzocaine and 2.0% tetracaine HCl) tested over a 60 minute session.	10
Total	40

Baseline characteristics

Characteristic	One Spray CTY-5339-A, Then One Spray CTY-5339-CB	2 Sprays CTY-5339-A, Then 1 Spray CTY-5339-CB +1 Spray Placebo	One Spray of CTY-5339-CB, Then One Spray CTY-5339-A	1 Spray CTY-5339-CB +1 Spray Placebo, Then 2 Sprays CTY-5339-A	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	10 Participants	10 Participants	10 Participants	10 Participants	40 Participants
Age, Continuous	28.6 years STANDARD_DEVIATION 9	25.0 years STANDARD_DEVIATION 1.8	26.4 years STANDARD_DEVIATION 2.8	27.6 years STANDARD_DEVIATION 6.4	26.9 years STANDARD_DEVIATION 5.7
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants	10 Participants	10 Participants	10 Participants	40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Height (inches)	66.7 inches STANDARD_DEVIATION 3.4	67.1 inches STANDARD_DEVIATION 2.6	68.3 inches STANDARD_DEVIATION 2.3	67.0 inches STANDARD_DEVIATION 2.9	67.3 inches STANDARD_DEVIATION 2.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	2 Participants	2 Participants	6 Participants	1 Participants	11 Participants
Race (NIH/OMB) Black or African American	1 Participants	1 Participants	0 Participants	2 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	6 Participants	6 Participants	3 Participants	7 Participants	22 Participants
Region of Enrollment United States	10 participants	10 participants	10 participants	10 participants	40 participants
Sex: Female, Male Female	6 Participants	6 Participants	4 Participants	9 Participants	25 Participants
Sex: Female, Male Male	4 Participants	4 Participants	6 Participants	1 Participants	15 Participants
Weight (lbs)	163.6 lbs STANDARD_DEVIATION 38.3	153.6 lbs STANDARD_DEVIATION 31.8	151.4 lbs STANDARD_DEVIATION 33.7	144.5 lbs STANDARD_DEVIATION 18	153.3 lbs STANDARD_DEVIATION 30.9

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 20	0 / 20	0 / 20
other Total, other adverse events	0 / 20	0 / 20	1 / 20	0 / 20
serious Total, serious adverse events	0 / 20	0 / 20	0 / 20	0 / 20

Outcome results

Primary

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

Population: Modified Intent-to-Treat (mITT) population: all randomized subjects who, as documented prior to the breaking of the study blind: (1) met all the inclusion and exclusion criteria and; (2) either completed the two 60 minute test sessions or returned to baseline values in all evaluation tests.

Arm	Measure	Value (MEAN)	Dispersion
One Spray CTY-5339-A	Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	44.6 minutes	Standard Deviation 17.8
One Spray CTY-5339-CB	Duration of Anesthesia as Measured by Heat Sensation Threshold (QST Heat) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	51.1 minutes	Standard Deviation 12.9

p-value: 0.13495% CI: [-20.38, 2.99]ANOVA

Primary

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

Arm	Measure	Value (MEAN)	Dispersion
One Spray CTY-5339-A	Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	17.9 minutes	Standard Deviation 12.9
One Spray CTY-5339-CB	Duration of Anesthesia as Measured by Pin Prick Test (PPT) for One Spray CTY-5339-A Compared to One Spray CTY-5339-CB	16.4 minutes	Standard Deviation 14.8

p-value: 0.32295% CI: [-3.06, 8.69]ANOVA

Secondary

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).