Comparison of Intranasal Kovacaine Mist, and Placebo for Anesthetizing Maxillary Teeth in Pediatric Patients

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 pediatric patients.

Detailed Description
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The study will employ a multi-center, randomized, double-blind, placebo-controlled, parallel-groups design to demonstrate the safety and efficacy of Kovacaine Mist delivered intranasally for inducing pulpal anesthesia of maxillary permanent teeth numbers 4 to 13 (maxillary right second premolar to maxillary left second premolar) or maxillary primary teeth numbers A to J (maxillary right second primary molar to maxillary left second primary molar) sufficient to allow completion of the Study Dental Procedure. The maxillary teeth will be categorized in two subsets, anterior teeth (permanent teeth numbers 6 to 11 and primary teeth numbers C to H) and posterior teeth (permanent teeth numbers 4, 5, 12, 13 and primary teeth numbers A, B, I, J). The intent is to treat 90 male and female subjects aged 3 to 17 years, inclusive, at 3 study sites, 2:1 randomization within each study site, and an overall goal of 60 subjects treated with Kovacaine Mist and 30 treated with placebo. Subjects will receive Kovacaine Mist or placebo (2:1) according to the kit randomization plan within three dosing strata (100 µL, 200 µL or 400 µL) based on subject weight at entry: subjects weighing 10 to <20 kg, 20 to <40 kg and ≥ 40 kg will be assigned to the 100 µL, 200 µL or 400 µL dose group, respectively. Recruitment will be from diverse pediatric dental patient populations. To ensure adequate representation in the 3 dose/weight groups, each stratum will contain at least 25% of subjects.

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 Pediatric Patients

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 3-17 years of age inclusive. Need for an operative restorative dental procedure and requiring local anesthesia on a single vital maxillary primary tooth (#A to J) or permanent tooth (#4 to13), with no evidence of pulpal pathology. Normal lip, nose, eyelid, and cheek sensation. Accompanied and/or represented by a parent or guardian able to comprehend and sign the informed consent document. Subject able to understand and provide assent to an age-appropriate subject assent form (as defined by local practice or regulation). Patient or parent/guardian able to communicate with the investigator and comply with the requirements of the protocol. Patency of the naris on the same side as the tooth undergoing the Study Dental Procedure (the Study Treatment Tooth). Exclusion Criteria: 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 lidocaine, 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 undergo urine testing on the day of, but prior to, study drug administration to rule out pregnancy.) Inadequately controlled thyroid disease of any type. Having received any investigational drug (including Kovacaine Mist) and/or participation in any clinical trial within 30 days of study participation. Frequent nose bleeds (≥ 5 per month). History of congenital or idiopathic methemoglobinemia. Presence of an upper respiratory infection and/or fever defined as body temperature ≥100.4° (38°C) on the day of and prior to study drug administration.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 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% - Subjects weighing more than 10kg and less than 20kg, will receive 1 spray of 100µL; Subjects weighing more than 20kg and less than 40kg, will receive 2 sprays of 100µL (200µL total); subjects weighting more than 40kg will receive 2 sprays of 200µL (400µL total); | Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%<br>* Intranasally administered regional anesthetic<br>* Other names: Kovacaine Mist;|
| Placebo Comparator: Placebo<br>Placebo - Subjects weighing more than 10kg and less than 20kg, will receive 1 spray of 100µL; Subjects weighing more than 20kg and less than 40kg, will receive 2 sprays of 100µL (200µL total); subjects weighting more than 40kg will receive 2 sprays of 200µL (400µL total); | Drug: Placebo<br>* Inactive ingredients supplied in identical nasal sprayer<br>* Other names: Intranasal administration of 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. | 100µL dose - at 10 minutes, +3 minute window; for subjects who receive the 200µL or 400µL dose - 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 Dosage Cohort. | 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. | 100µL dose - at 10 minutes, +3 minute window; for subjects who receive the 200µL or 400µL dose - at 15 minutes, +3 minute window | 
| Number of Participants Who Completed the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic. by Age Group (3-5, 6-11, and 12-17 Years Old, Inclusive). | 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. | 100µL dose - at 10 minutes, +3 minute window; for subjects who receive the 200µL or 400µL dose - at 15 minutes, +3 minute window | 
| Incidence of Adverse Events (AEs) by Dosage Cohort | Patients with AEs | from baseline to 24 hours following drug administration | 
| Incidence of Adverse Events (AEs) by Age Group | Patients with AEs | from baseline to 24 hours following drug administration | 
| Results of Naris Examination (NE) - Patency and Ulcerations | The investigators evaluated the treatment naris for patency and ulcerations. Patency was evaluated as followed: The nostril not used for dosing study drug was manually occluded and the subject was asked to sniff gently. Airflow in the naris was used to determine if it was patent (yes) or not (no). For ulcers, the investigators performed a visual examination for the presence of ulcers and recorded if they were present (yes) or not (no). | 120 minutes post drug administration | 
| Maximum Change From Baseline in Heart Rate |  | from baseline to 24 hours following drug administration | 
| Maximum Change From Baseline in Systolic Blood Pressure |  | from baseline to 24 hours following drug administration | 
| Maximum Change From Baseline in Diastolic Blood Pressure |  | from baseline to 24 hours following drug administration | 
| Results of Naris Examination (NE) - Color | The investigators performed a visual inspection and evaluated the treatment naris for color of the mucosa. The investigator determined what color (Pink, Slightly Red, Red) best matched and recorded the results. | 120 minutes post drug administration | 
| Results of Naris Examination (NE) - Inflammation |  | 120 minutes post drug administration | 
| Results of Naris Examination (NE) - Bleeding |  | 120 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