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

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. A total of 140 subjects, randomized 2:2:1 (Kovacaine Mist:Tetracaine alone:Placebo) will be enrolled to achieve 125 completed subjects; a total of 50 Kovacaine Mist subjects, 50 tetracaine alone subjects and 25 placebo subjects. Recruitment will be from diverse dental patient populations. At the two study sites, a balanced enrollment of 70 subjects each is planned to allow for a potential 10% drop-out rate.

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>|
| Placebo Comparator: Placebo, 3 sprays unilateral<br>Placebo | Drug: Placebo<br>* 3 unilateral intranasal sprays per dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no). |  | 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 and greater palatine foramen soft-tissue was tested with a probe | at 15 minutes with a 3 minute window | 
| Number of Participants With Heart Rate Higher Than 125 Bpm |  | at any time within 120 minutes following drug administration | 
| Number of Participants With 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 90 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 15 mm Hg and to a Value Lower Than 90 mm Hg |  | at any time within 120 minutes following drug administration | 
| Absolute Maximum Change From Baseline in Systolic Blood Pressure and 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 an alcohol swab. | 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 | 
| Absolute Maximum Change From Baseline in Heart Rate |  | 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