Comparison of Intranasal Kovacaine Mist, 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, 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 maxillary teeth will be categorized in two subsets, anteriors (teeth numbers 6 to 11) and premolars (teeth numbers 4, 5, 12 and 13). The intent is to treat 150 subjects at 3 study sites, 2:1 randomization within each study site, and an overall goal of 100 subjects treated with Kovacaine Mist and 50 treated with placebo. Recruitment will be from diverse dental patient populations with at least 25% of subjects over 50 years of age. Randomization will be within strata defined by age (≤50 and >50 years).

Official Title
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A Phase 3, Multi-Center, Randomized, Double-Blind, Parallel-Groups Clinical Trial Comparing the Efficacy and Safety of Intranasally Administered Kovacaine Mist 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: 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 (anterior or premolar tooth #4 to #13) 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 (the treatment tooth). Resting heart rate (HR) between 55 and 100 beats per minute (bpm), inclusive. Seated systolic blood pressure (SBP) between 95 and 150 mm Hg, inclusive, and seated diastolic blood pressure (DBP) between 60 and 100 mm Hg, inclusive. Exclusion Criteria: Inadequately controlled hypertension (blood pressure greater than 150/100 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 24 hours preceding study entry. 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 the 30 days prior to study participation. 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<br>Tetracaine HCl 3% and Oxymetazoline HCl 0.05% - 2 sprays will be administered at the start of the procedure, if anesthesia is insufficient, a third spray will be administered. | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* The study drug is regional anesthetic delivered intranasally on the same side as the operative tooth<br>* Other names: Kovacaine Mist;|
| Placebo Comparator: Placebo<br>Placebo - 2 sprays will be administered at the start of the procedure, if anesthesia is insufficient, a third spray will be administered. | Drug: Placebo<br>* The placebo spray was identical in appearance to and was administered in the same volume and manner as the active ingredient.<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 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, +3 minute window | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Completed the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic by Age Group (≤50 and >50 Years) | 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. This outcome is broken down by age group, 1) less than 50 years of age and 2) 50 years of age and older. | at 15 minutes (+3 minute window) or 25 minutes (+3 minute window) if third intranasal spray is used | 
| 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/or 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/or to a Value Lower Than 90 mm Hg |  | at any time within 120 minutes following study drug administration | 
| Number of Participants With an Increase From Baseline in Diastolic Blood Pressure Greater Than or Equal to 15 mm Hg and/or to a Value Higher Than 105 mm Hg |  | at any time within 120 minutes following study drug administration | 
| Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 10 mm Hg and/or to a Value Lower Than 50 mm Hg |  | at any time within 120 minutes following study drug administration | 
| Maximum Change From Baseline in Heart Rate |  | from baseline to 120 minutes following drug administration | 
| Maximum Change From Baseline in Systolic Blood Pressure |  | from baseline to 120 minutes following drug administration | 
| 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 | 
| Alcohol Sniff Test | The change from screening in the the distance from the nose (in centimeters) that a patient is able to detect the smell of alcohol on a cotton ball. | administered at approximately 24 hours after 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 | 

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