Comparison of Intranasal Kovacaine Mist, Tetracaine Alone, and Placebo for Anesthetizing Maxillary Teeth in Adults

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of Kovacaine Mist, Tetracaine only, and Placebo for inducing pulpal anesthesia of the maxillary teeth in adults.

Detailed Description
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The study will employ a multi-center, randomized, double-blind, placebo-controlled, parallel-groups design to assess the safety and efficacy of Kovacaine Mist delivered intranasally for inducing pulpal anesthesia of maxillary teeth numbers 4 to 13 (maxillary right second premolar to maxillary left second premolar) sufficient to allow completion of the Study Dental Procedure. The intent is to treat 110 subjects, with enrollment balanced evenly between the 2 study sites, 2:2:1 randomization within each study site and an overall goal of 44 subjects treated with Kovacaine Mist, 44 treated with Tetracaine alone, and 22 treated with Placebo. Recruitment will be from diverse dental patient populations.

Official Title
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A Phase III, Multi-Center, Randomized, Double-Blind, Parallel-Groups Clinical Trial Comparing the Efficacy and Safety of Intranasally Administered Kovacaine Mist to Tetracaine Alone and to Placebo for Anesthetizing Maxillary Teeth in Adults

Conditions
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Anesthesia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older. Need for an operative restorative dental procedure requiring local anesthesia for a single vital maxillary tooth (other than a maxillary first, second, or third molar) with no evidence of pulpal pathology. Normal lip, nose, eyelid, and cheek sensation. Able to understand and sign the study informed consent document, communicate with the investigators, and understand and comply with the requirements of the protocol. Patency of the naris ipsilateral to the tooth undergoing the Study Dental Procedure. Resting heart rate (HR) between 55 and 100 beats per minute (bpm), inclusive. Seated systolic blood pressure (SBP) between 95 and 140 mm Hg, inclusive and seated diastolic blood pressure (DBP) between 60 and 90 mm Hg, inclusive. Exclusion Criteria: Inadequately controlled hypertension (blood pressure greater than 140/90 mm Hg). Inadequately controlled active thyroid disease of any type. Frequent nose bleeds (≥ 5 per month). Having received dental care requiring a local anesthetic within the last 24 hours. History of allergy to or intolerance of tetracaine, benzyl alcohol, other ester local anesthetics, or para-aminobenzoic acid (as found in PABA-containing sunscreen). History of allergy or hypersensitivity to articaine, oxymetazoline, epinephrine, or sulfite preservatives. Use of a monoamine oxidase inhibitor within the 3 weeks preceding study entry. Nursing, pregnant, suspected of being pregnant, or trying to become pregnant. (Females of child-bearing potential will be required to take a urine pregnancy test on the day of, but prior to, study drug administration to rule out pregnancy.) Having received any investigational drug and/or participation in any clinical trial within 30 days prior to study participation. Having used oxymetazoline or phenylephrine nasal spray, nasal irrigation, or other nasal or oral decongestant on the day of the study procedure. History of congenital or idiopathic methemoglobinemia

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kovacaine Mist, 3 sprays unilateral<br>Tetracaine HCl 3% and Oxymetazoline HCl 0.05% | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* 3 unilateral intranasal sprays per dose<br>* Other names: Kovacaine Mist;|
| Experimental: Tetracaine Only, 3 sprays unilateral<br>Tetracaine HCl 3% | Drug: Tetracaine HCl 3%<br>* 3 unilateral intranasal sprays per dose<br>* Other names: Active control;|
| Placebo Comparator: Placebo, 3 sprays unilateral<br>Placebo | Drug: Placebo<br>* 3 unilateral intranasal sprays per dose<br>* Other names: Inactive ingredients;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Completed the Study Dental Procedure After Without Need for Rescue by Injection of Local Anesthetic. | If the participant does not have sufficient anesthesia to complete the Study Dental Procedure, the participant is given a rescue injection of local anesthetic and is considered a failure for this outcome. | at 15 minutes with a 3 minute window | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoral Soft-tissue Anesthesia (Yes/no) | Number of patients who reported no pain when incisive papilla soft-tissue was tested with a probe at designated timepoints | at Baseline, 15, 30, 45, 60, 90, and 120 minutes with a 3 minute window | 
| Number of Participants With a Heart Rate Higher Than 125 Bpm |  | at any time within 120 minutes following drug administration | 
| Number of Participants With a Heart Rate Lower Than 50 Bpm |  | at any time within 120 minutes following drug administration | 
| Number of Participants With an Increase From Baseline in Systolic Blood Pressure Greater Than or Equal to 25 mm Hg and to a Value Higher Than 160 mm Hg |  | at any time within 120 minutes following drug administration | 
| Number of Participants With a Decrease From Baseline in Systolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Lower Than 90 mm Hg |  | at any time within 120 minutes following drug administration | 
| Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and to a Value Higher Than 105 mm Hg |  | at any time within 120 minutes following drug administration | 
| Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 10 mm Hg and to a Value Lower Than 50 mm Hg |  | at any time within 120 minutes following drug administration | 
| Absolute Maximum Change From Baseline in Heart Rate |  | from baseline to 120 minutes following drug administration | 
| Absolute Maximum Change From Baseline in Systolic Blood Pressure |  | from baseline to 120 minutes following drug administration | 
| Absolute Maximum Change From Baseline in Diastolic Blood Pressure |  | from baseline to 120 minutes following drug administration | 
| The Profile Over Time of Heart Rate |  | from baseline to 120 minutes following drug administration | 
| The Profile Over Time of Systolic Blood Pressure |  | from baseline to 120 minutes following drug administration | 
| The Profile Over Time of Diastolic Blood Pressure |  | from baseline to 120 minutes following drug administration | 
| Alcohol Sniff Test | The distance from the nose (in centimeters) that a patient is able to detect the smell of alcohol on an alcohol swab. | administered at baseline, 120 minutes and approximately 24 hours after drug administration | 
| Intraoral Soft-tissue Anesthesia (Onset and Duration) | Mean onset and duration of incisive papilla anesthesia based on number of patients who reported no pain when soft-tissue was tested with a probe at designated timepoints | up to 120 mins post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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operative, dental procedure