Safety and Effectiveness of Kovacaine Nasal Spray for Dental Anesthesia

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II, Single-Center, Randomized, Double-Blind, Active-Treatment-Controlled, Parallel-Group Study of the Efficacy of Kovacaine Nasal Spray for Anesthetizing Maxillary Teeth in Healthy Dental Patients

Conditions
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Dental Anesthesia Efficacy

Intervention / Treatment
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* Drug: 3% tetracaine HCL with 0.05% oxymetazoline HCL
* Drug: Lidocaine Injection


Participation Criteria
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Eligibility Criteria
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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

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kovacaine Nasal Spray<br>3% tetracaine HCL with 0.05% oxymetazoline HCL - Delivered via 3 sprays (100 uL) in each nostril | Drug: 3% tetracaine HCL with 0.05% oxymetazoline HCL<br>* 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.<br>|
| Active Comparator: Lidocaine Injection<br>.5 to 1 catridge of 2% lidocaine HCL with 1:100,000 epinephrine | Drug: Lidocaine Injection<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Continuous throughout dental treatment period (up to 60 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Baseline, 15, 20, 30, 40, 50, 60, 80, 100, 120 minutes | 
| Maximum Change in Pulse From Baseline | Maximum change from Baseline at any time point. | Baseline, 15, 20, 30, 40, 50, 60, 120 minutes | 
| Maximum Change in Blood Pressure From Baseline | Maximum change from Baseline at any time point. | Baseline, 15, 20, 30, 40 50, 60, 120 minutes | 
| Maximum Change in Pulse Oximetry From Baseline | Maximum change from Baseline at any time point | Baseline, 15, 20, 30, 40, 50, 60, 120 minutes |