Comparison of Anesthetic Efficacy of Bilateral and Unillateral Application of Kovacaine Mist in Healthy Volunteers

Study Overview
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Brief Summary
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To compare the efficacy of Kovacaine Mist administered bilaterally to that of Kovacaine Mist administered unilaterally with respect to global profound pulpal anesthesia in target teeth numbers 4-13.

Detailed Description
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Qualified and consenting healthy subjects will be randomly assigned in a double-blind manner to sequences of four randomly ordered study periods with inter-treatment washout periods of 3 to 14 days. The four study regimens, which will be applied in random order will be: Regimen1. Three sprays of Kovacaine Mist in each nostril (bilateral dosing); Regimen 2. Three sprays of Kovacaine Mist in the right nostril and three sprays of placebo in the left nostril (right-sided unilateral dosing); Regimen 3. Three sprays of Kovacaine Mist in the left nostril and three sprays of placebo in the right nostril (left-sided unilateral dosing); Regimen 4. Three sprays of placebo in each nostril (placebo dosing). During each testing period, eight representative maxillary teeth (#s 3, 4, 6, 8, 9, 11, 13 and 14) will be assessed for anesthesia using standard EPT testing. EPT testing will be conducted on the eight representative teeth at the following time points (minutes relative to the first spray of study drug): T-5, T3, T7, T11, T16, T21, T26T31, T41, T51, T61, T76, T91, T121, T151, and T181. If EPT testing of a target tooth is not possible (e.g., missing or does not meet inclusion criterion #2) tooth substitution is permissible. For molar teeth, #2 may replace #3 and #15 may replace #14. For premolar teeth, #5 may replace #4 and #12 may replace #13. The same replacements will be made for all testing sessions, and the actual teeth tested will be documented in the CRF.

Official Title
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Phase 1, Randomized, Double-Blind, Placebo-Controlled, 4-Period, Complete Cross-Over Comparison of the Anesthetic Efficacy of Bilateral and Unilateral Application of Kovacaine Mist in Healthy Volunteers

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
* Drug: Placebo spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older. Eight representative maxillary teeth [(3 (or 2), 4 (or 5), 6, 8, 9, 11, 13 (or 12), and 14 (or15)] free of observable decay (or other pathology), crowns or veneers, all of which have EPT values of 10-50 at screening. Normal lip, nose, eyelid, palate, and cheek sensation. Patency of both left and right nasal airways. Ability to understand and willingness to sign the study informed consent form, communicate with study investigators, and understand and comply with the requirements of the study protocol. Exclusion Criteria: Poorly controlled hypertension (blood pressure greater than 150/90 mmHg) or history of coronary heart disease. Diabetes mellitus. Any active thyroid disease other than S/P thyroidectomy on thyroid hormone replacement with TSH values in the normal range. History or presence of narrow-angle glaucoma. Prostatic enlargement. History of sinus/nasal surgery that, in the opinion of the investigator, could confound study results. History of frequent nose bleeds. Receipt of dental care requiring a local anesthetic within the last 24 hours. History of allergy to or intolerance of tetracaine, benzyl alcohol, benzocaine, other ester local anesthetics, succinylcholine, or para-aminobenzoic acid (as found in PABA-containing sunscreens). History of allergy or hypersensitivity to articaine, oxymetazoline, epinephrine, or sulfite antioxidants. History of drug abuse. Use of a monoamine oxidase inhibitor within the 3 weeks immediately prior to anticipated study participation. Nursing, pregnant, suspected of being pregnant, or trying to become pregnant. (Females will be required to undergo pregnancy testing to rule out pregnancy) Use of any investigational drug and/or participation in a clinical research trial within 30 days of the first study dosing day. Requirement for uninterrupted use of any medication with actions that might, in the opinion of the involved investigator, confound interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kovacaine Mist<br>3 sprays of Kovacaine Mist (Tetracaine HCl 3% and Oxymetazoline HCl 0.05%) in each nostril (bilateral dosing) administered 4 minutes apart | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* Active Spray with deliverable volume of 0.1 mL<br>* Other names: Kovacaine Mist;|
| Active Comparator: Kovacaine Mist and Placebo<br>3 sprays of Kovacaine Mist (Tetracaine HCl 3% and Oxymetazoline HCl 0.05%) in the right nostril and three sprays of placebo in the left nostril (right-sided unilateral dosing) administered 4 minutes apart | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* Active Spray with deliverable volume of 0.1 mL<br>* Other names: Kovacaine Mist;Drug: Placebo spray<br>* Aqueous solution to deliver 0.1 mL per unit<br>* Other names: Placebo;|
| Active Comparator: Placebo and Kovacaine Mist<br>3 sprays of Kovacaine Mist (Tetracaine HCl 3% and Oxymetazoline HCl 0.05%) in the left nostril and 3 sprays of placebo in the right nostril (left-sided dosing) administered 4 minutes apart | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* Active Spray with deliverable volume of 0.1 mL<br>* Other names: Kovacaine Mist;Drug: Placebo spray<br>* Aqueous solution to deliver 0.1 mL per unit<br>* Other names: Placebo;|
| Placebo Comparator: Placebo spray<br>3 sprays of placebo in each nostril administered 4 minutes apart | Drug: Placebo spray<br>* Aqueous solution to deliver 0.1 mL per unit<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of GPPA by teeth reaching an EPT of 80 | Achievement of Global Profound Pulpal Anesthesia (GPPA) as having all three target maxillary teeth [nos. 4(or 5), 6, and 8 for the right side or nos. 9, 11, and 13 (or 12) for the left-side] reach an EPT of 80 within 20 minutes of the final spray of study drug | 20 minutes of final spray | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of GPPA for bilateral versus placebo administration |  | 20 minutes of final spray | 
| Incidence of PPA for individual teeth | For all individually EPT-tested teeth the incidence of Profound Pulpal Anesthesia (PPA) defined as reaching an EPT of 80 within 20 minutes, with unilateral and bilateral drug administration | 181 minutes | 
| Time to onset and duration of PPA | For all individually EPT-tested teeth achieving PPA, time to onset and duration of PPA for unilateral and bilateral drug administration | 181 minutes | 
| Mean highest EPT value reached for first molars (#3 and 14) |  | 181 minutes | 
| Incidence of induction of PPA following the first, second and third doses of active drug administered unilaterally and bilaterally |  | 181 minutes | 
| Correlation between positive responses on Subjective Numbness Assessment (DNA) and incidence of global EPT scores of 80 |  | 181 minutes | 
| Systolic Blood Pressure |  | 181 minutes | 
| Diastolic Blood Pressure |  | 181 minutes | 
| Heart Rate |  | 181 minutes | 
| Adverse experiences spontaneously reported | Adverse experiences spontaneously reported by subjects, or observed by study personnel including those encountered on nasal and airway examination (NAE), incidence rates for systolic and diastolic blood pressure and heart rate exceeding +/- 25% of pre-study values | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dental Anesthesia