Open-Label Study of Efficacy and Recommended Dose of Kovacaine Mist for Anesthetizing Maxillary Teeth

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of and recommended dosing regimen for unilateral administration of Kovacaine Mist in inducing pulpal anesthesia of the maxillary teeth for dental procedures.

Detailed Description
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This is a Phase II single-center, open-label clinical trial with three dosing regimens, designed to determine the efficacy and optimal dose of the Kovacaine Mist intranasal delivery system for inducing pulpal anesthesia of maxillary teeth numbers 4-13 (maxillary right second premolar to maxillary left second premolar). Kovacaine will be administered intranasally on the same side of the midline as the tooth on which the procedure will be performed in three dosing cohorts [four 100 μL, two 200 μL, or one 200 μL spray(s)] of 10 subjects each. The first cohort receiving 4 sprays will be completed before initiating study of the remaining two cohorts, which will be treated using a randomized, parallel-group design. Administration: Subjects in the 4- and 2-spray cohorts will be administered the same total dose of 12 mg tetracaine HCl/0.2 mg oxymetazoline HCl. The 4-spray cohort will be treated with a sequence of four 100-μL sprays at intervals of 4 minutes. The 2-spray cohort will be treated with a sequence of two 200 μL sprays 4 minutes apart. The 1-spray cohort will be administered one 200 μL spray, a total dose of 6 mg tetracaine HCl/0.1 mg oxymetazoline HCl, which is half the dose of the 2-spray cohort. Rescue: If the study drug does not provide sufficient anesthesia to allow for completion of the dental procedure, a rescue injection of articaine will be administered.

Official Title
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A Phase II, Single-Site, Open-Label Clinical Trial To Evaluate The Efficacy And Recommended Dosing Regimen Of Kovacaine Mist Administered Unilaterally For Anesthetizing Maxillary Teeth In Healthy Dental Patients

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Kovacaine Mist 0.1 mL x 4 sprays
* Drug: Kovacaine Mist 0.2 mL x 2 sprays
* Drug: Kovacaine Mist 0.2 mL x 1 spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects who are 18 years of age or older; requiring an operative restorative procedure on a single maxillary tooth with no evidence of pulpal pathology requiring local anesthesia; having normal lip, nose, eyelid, and cheek sensations; able to understand and sign the informed consent document, communicate with the investigators, and understand and comply with the requirements of the protocol; having patency of naris on same side of head as tooth requiring the dental procedure. Exclusion Criteria: Inadequately controlled hypertension (blood pressures greater than 150/90) or untreated coronary heart disease; inadequately controlled thyroid disease including Hashimoto's thyroiditis and partial thyroidectomy; having frequent nose bleeds (10 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, benzocaine, other ester local anesthetics, or para-aminobenzoic acid (as found in PABA-containing sunscreens); history of allergy or hypersensitivity to articaine, oxymetazoline, epinephrine, or sulfite preservatives; history of taking a monoamine oxidase inhibitor within the past 3 weeks; are nursing, pregnant, suspected of being pregnant, or trying to become pregnant. (Females will be required to take a urine pregnancy test on the day of but prior to study drug administration to rule out pregnancy); having used any investigational drug and/or participated in any clinical research trial within 30 days of baseline enlarged prostate narrow angle glaucoma use of oxymetazoline or phenylephrine nasal spray or oral decongestant on the day of the study congenital or idiopathic methemoglobinemia diabetes mellitus

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kovacaine Mist 0.1 mL x 4 sprays<br>Total dose: 12 mg tetracaine/0.2 mg oxymetazoline | Drug: Kovacaine Mist 0.1 mL x 4 sprays<br>* Dose = 4 intranasal sprays of study drug delivered at 4-minute intervals.<br>* Other names: Tetracaine HCl 3% and HCl 0.05%;|
| Experimental: Kovacaine Mist 0.2 mL x 2 sprays<br>Total dose: 12 mg tetracaine/0.2 mg oxymetazoline | Drug: Kovacaine Mist 0.2 mL x 2 sprays<br>* Dose = 2 intranasal sprays of study drug delivered at 4-minute intervals.<br>* Other names: Tetracaine HCl 3% and HCl 0.05%;|
| Experimental: Kovacaine Mist, 0.2 mL x 1 spray<br>Total dose: 6 mg tetracaine/0.1 mg oxymetazoline | Drug: Kovacaine Mist 0.2 mL x 1 spray<br>* Dose = 1 intranasal spray of study drug<br>* Other names: Tetracaine HCl 3% and HCl 0.05%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure |  | at 15 minutes, with +10 minute window | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. |  | 60 minutes | 
| The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. |  | 60 minutes | 
| Naris Examination | Number of patients with an abnormal naris examination finding. | 60 minutes post drug administration | 

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