Dental Anesthesia Efficacy
Conditions
Brief summary
The purpose of this study was to determine the safety and efficacy of Kovacaine Mist (3% tetracaine HCl with 0.05% oxymetazoline HCl) for anesthesia of the maxillary teeth for dental procedures.
Detailed description
The primary objective of this single-center, randomized, double-blind, active-controlled, parallel-group study was to determine if Kovacaine Mist provided anesthesia of the maxillary teeth sufficient for the performance of dental procedures. Secondary objectives included a determination of whether Kovacaine Mist provided anesthesia of the soft tissue and to evaluate the safety and tolerability of Kovacaine Mist and sham injection as compared to sham nasal spray and 2% lidocaine hydrochloride with 1:100,000 epinephrine submucosal injection and as determined by changes in vital signs and reports of side effects and adverse events.
Interventions
Each subject received both an injection along with 3 sprays of isotonic saline sham in each nostril; a 4-minute interval between every set of sprays.
DRUG3% tetracaine HCL with 0.05% oxymetazoline HCL
1 sham injection along with 3 sprays of Kovacaine Nasal Spray in each nostril; a 4-minute interval between every set of sprays. The total dose of 3% tetracaine HCL with 0.05% oxymetazoline HCL was 18 mg/0.3 mg.
Sponsors
Ground Zero Pharmaceuticals
Rho, Inc.
St. Renatus, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female between 18 and 65 years of age * Sufficiently healthy as determined by the investigator to receive the test and control medications and undergo the scheduled dental procedure * Required an operative restorative procedure on a single maxillary tooth, other than a maxillary second or third molar, with treatment time not expected to exceed 60 minutes * Could breathe through both nostrils * Had normal lip, nose, eyelid, and cheek sensations * Could understand and sign the informed consent document * Could communicate with the investigator * Could understand and comply with the requirements of the protocol
Exclusion criteria
* Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, cardiovascular, psychiatric, musculoskeletal, neurologic, genitourinary, infective, inflammatory, immunological, dermatological, or connective tissue disease or disorder or a clinically relevant history or presence of angle-closure glaucoma * Clinically relevant sinus/nasal surgical history * Baseline Visual Analog Scale value of \> 36 (or greater than weak) at the treatment site * Had not had dental work requiring a local anesthetic within the last 24 hours or had taken pain medications within the last 48 hours * Required prophylactic antibiotics for subacute bacterial endocarditis (infectious endocarditis) * Allergic to or intolerant of tetracaine, benzocaine, other ester local anesthetics, or p-aminobenzoic acid (PABA), as found in PABA-containing sunscreens * Allergic to or intolerant of oxymetazoline, epinephrine, or preservatives in their solutions * Had a current condition, such as nasal congestion or sinus infection, that may have influenced responses to study medications * History of alcoholism and/or drug abuse * Had taken a monamine oxidase inhibitor within the past 3 weeks * Were nursing, pregnant, suspected of being pregnant, or trying to become pregnant (females were required to take a urine pregnancy test to rule out pregnancy) * Had used any investigational drug and/or participated in any clinical trial within 30 days of baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulpal Anesthesia | Continuous throughout dental treatment period (up to 60 minutes) | Number of participants who did not need rescue anesthesia to complete the study dental procedure, i.e. Kovacaine provided enough pulpal anesthesia to complete a dental procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Change in Pulse From Baseline | Baseline, 15, 20, 30, 40, 50, 60, 120 minutes | Maximum change from Baseline at any time point. |
| Maximum Change in Blood Pressure From Baseline | Baseline, 15, 20, 30, 40 50, 60, 120 minutes | Maximum change from Baseline at any time point. |
| Maximum Change in Pulse Oximetry From Baseline | Baseline, 15, 20, 30, 40, 50, 60, 120 minutes | Maximum change from Baseline at any time point |
| Soft Tissue Anesthesia Duration | Baseline, 15, 20, 30, 40, 50, 60, 80, 100, 120 minutes | Assessment of pain using a Rotadent sensor probe, applying up to 20 grams/cm\^2 at the tissue site. At each time point, participants were asked if they felt pain from the sensor probe at each site location in the mouth. The four sites were: * Site 1: Distal to the apex of the tooth in the position of the maxillary first premolar at the deepest point in the buccal vestibule * Site 2: Apical to the maxillary lateral incisor at the deepest point in the labial vestibule * Site 3: Incisive papilla * Site 4: At the confluence of the alveolar process and hard palate medial to the maxillary second premolar (near the greater palatine foramen) |
Countries
United States
Participant flow
Recruitment details
Recruitment completed within the month of December, 2008. Subjects were primarily recruited from University of Buffalo staff and students.
Participants by arm
| Arm | Count |
|---|---|
| Kovacaine Nasal Spray | 30 |
| Lidocaine Injection | 15 |
| Total | 45 |
Baseline characteristics
| Characteristic | Lidocaine Injection | Kovacaine Nasal Spray | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 30 Participants | 45 Participants |
| Age, Continuous | 40.8 years STANDARD_DEVIATION 15.3 | 38.6 years STANDARD_DEVIATION 12.8 | 39.3 years STANDARD_DEVIATION 13.6 |
| Region of Enrollment United States | 15 participants | 30 participants | 45 participants |
| Sex: Female, Male Female | 3 Participants | 16 Participants | 19 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 30 | 0 / 15 |
| serious Total, serious adverse events | 0 / 30 | 0 / 15 |
Outcome results
Primary
Pulpal Anesthesia
Number of participants who did not need rescue anesthesia to complete the study dental procedure, i.e. Kovacaine provided enough pulpal anesthesia to complete a dental procedure.
Time frame: Continuous throughout dental treatment period (up to 60 minutes)
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Kovacaine Nasal Spray | Pulpal Anesthesia | 25 participants |
| Lidocaine Injection | Pulpal Anesthesia | 14 participants |
Secondary
Maximum Change in Blood Pressure From Baseline
Maximum change from Baseline at any time point.
Time frame: Baseline, 15, 20, 30, 40 50, 60, 120 minutes
Population: Intention to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Kovacaine Nasal Spray | Maximum Change in Blood Pressure From Baseline | Systolic blood pressure | 4.50 mmHG | Standard Deviation 17.39 |
| Kovacaine Nasal Spray | Maximum Change in Blood Pressure From Baseline | Diastolic blood pressure | -2.67 mmHG | Standard Deviation 13.73 |
| Lidocaine Injection | Maximum Change in Blood Pressure From Baseline | Systolic blood pressure | 3.43 mmHG | Standard Deviation 10.62 |
| Lidocaine Injection | Maximum Change in Blood Pressure From Baseline | Diastolic blood pressure | -5.07 mmHG | Standard Deviation 8.49 |
Secondary
Maximum Change in Pulse From Baseline
Maximum change from Baseline at any time point.
Time frame: Baseline, 15, 20, 30, 40, 50, 60, 120 minutes
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kovacaine Nasal Spray | Maximum Change in Pulse From Baseline | -11.13 beats per minute | Standard Deviation 9.68 |
| Lidocaine Injection | Maximum Change in Pulse From Baseline | -6.60 beats per minute | Standard Deviation 15.58 |
Secondary
Maximum Change in Pulse Oximetry From Baseline
Maximum change from Baseline at any time point
Time frame: Baseline, 15, 20, 30, 40, 50, 60, 120 minutes
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kovacaine Nasal Spray | Maximum Change in Pulse Oximetry From Baseline | 0.17 SpO2 | Standard Deviation 2.39 |
| Lidocaine Injection | Maximum Change in Pulse Oximetry From Baseline | -0.80 SpO2 | Standard Deviation 2.76 |
Secondary
Soft Tissue Anesthesia Duration
Assessment of pain using a Rotadent sensor probe, applying up to 20 grams/cm\^2 at the tissue site. At each time point, participants were asked if they felt pain from the sensor probe at each site location in the mouth. The four sites were: * Site 1: Distal to the apex of the tooth in the position of the maxillary first premolar at the deepest point in the buccal vestibule * Site 2: Apical to the maxillary lateral incisor at the deepest point in the labial vestibule * Site 3: Incisive papilla * Site 4: At the confluence of the alveolar process and hard palate medial to the maxillary second premolar (near the greater palatine foramen)
Time frame: Baseline, 15, 20, 30, 40, 50, 60, 80, 100, 120 minutes
Population: Intention to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Kovacaine Nasal Spray | Soft Tissue Anesthesia Duration | Site 1 Duration | 21.1 Minutes | Standard Deviation 16.9 |
| Kovacaine Nasal Spray | Soft Tissue Anesthesia Duration | Site 3 Duration | 31.8 Minutes | Standard Deviation 19.9 |
| Kovacaine Nasal Spray | Soft Tissue Anesthesia Duration | Site 2 Duration | 16.1 Minutes | Standard Deviation 16.9 |
| Kovacaine Nasal Spray | Soft Tissue Anesthesia Duration | Site 4 Duration | 31.4 Minutes | Standard Deviation 24.1 |
| Lidocaine Injection | Soft Tissue Anesthesia Duration | Site 2 Duration | 32.1 Minutes | Standard Deviation 4.9 |
| Lidocaine Injection | Soft Tissue Anesthesia Duration | Site 1 Duration | 34.2 Minutes | Standard Deviation 21 |
| Lidocaine Injection | Soft Tissue Anesthesia Duration | Site 4 Duration | 29.3 Minutes | Standard Deviation 27.6 |
| Lidocaine Injection | Soft Tissue Anesthesia Duration | Site 3 Duration | 25.0 Minutes | Standard Deviation 18.3 |