Dose-Ranging Study of Intranasal Kovacaine Mist in Pediatric Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of intranasally administered Kovacaine Mist for anesthetizing maxillary teeth in pediatric subjects.

Detailed Description
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This is a single-center, open-label, randomized, parallel-groups, dose-ranging study to assess the efficacy and safety of intranasally administered Kovacaine Mist for anesthetizing maxillary teeth in pediatric subjects. The study will employ an open-label design to determine the lowest effective doses (LEDs), and assess the safety and efficacy of Kovacaine Mist administered intranasally for inducing pulpal anesthesia of maxillary primary teeth numbers A to J and maxillary permanent teeth numbers 4 to 13 (maxillary right second premolar to maxillary left second premolar) sufficient to allow completion of the Study Dental Procedure, and will be carried out in healthy children of either sex between the ages of 3 and 17 years, inclusive.

Official Title
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A Phase 2, Single-Center, Open-Label, Randomized, Parallel-Groups, Dose-Ranging Study to Assess the Efficacy and Safety of Intranasally Administered Kovacaine Mist for Anesthetizing Maxillary Teeth in Pediatric Subjects

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: 400uL of Kovacaine Mist
* Drug: 200uL of Kovacaine Mist
* Drug: 120uL of Kovacaine Mist


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 on a single vital maxillary primary tooth (#A to J) or permanent tooth (#4 to13), other than a maxillary permanent first, second or third molar, requiring local anesthesia with an expected treatment duration not exceeding 60 minutes. 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. If age 8 and above, able to understand and provide informed assent. Patient or parent/guardian able to communicate with the investigator and comply with the requirements of the protocol. Patency of the naris ipsilateral to the tooth undergoing the Study Dental Procedure. Minimum weight: Subjects in Cohorts A and B (age 6 and above) must weigh at least 20kg (44 lb.). Subjects in Cohort C (age 3 and above) must weigh at least 10kg (22 lb.). Exclusion Criteria: Dental care requiring a local anesthetic within the 24 hours prior to anticipated study participation. 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 take a urine pregnancy test on the day of, but prior to, study drug administration to rule out pregnancy.) Inadequately controlled thyroid disease of any type. Use of 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). Anticipated need for use of 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. Clinically relevant history of sinus/nasal surgery, recent epistaxis, nasal congestion or sinus infections, or use of a sinus medication within the 48 hours prior to anticipated study participation. History of alcoholism and/or drug abuse. Pulpal pathology in the index tooth. Anticipated need for use of nitrous oxide before or during the Study Dental Procedure. Any chronic or currently uncontrolled psychogenic, neurological, endocrine, pulmonary, cardiovascular, renal, gastrointestinal or hepatic disease or condition with manifestations that might confound interpretation of study results or make receipt of study medication a source of risk for adverse outcome. Fever defined as body temperature ≥100° (37°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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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kovacaine Mist High Dose<br>400uL of Kovacaine Mist, as 2 sprays of 200uL. | Drug: 400uL of Kovacaine Mist<br>* 2 unilateral intranasal sprays of 200uL each.<br>* Other names: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%;|
| Experimental: Kovacaine Mist Mid Dose<br>200uL of Kovacaine Mist, as 2 sprays of 100uL. | Drug: 200uL of Kovacaine Mist<br>* 2 unilateral intranasal sprays of 100uL each.<br>* Other names: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%;|
| Experimental: Kovacaine Mist Low Dose<br>120uL of Kovacaine Mist, as 2 sprays of 60uL. | Drug: 120uL of Kovacaine Mist<br>* 2 unilateral intranasal sprays of 60uL each.<br>* Other names: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%;|

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 14 minutes with a 3 minute window | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Naris Examination (NE) to Assess Reactions to the Study Drug. | The principal investigator will perform a visual inspection to note number of participants at post-dose that have a ulceration, inflammation or minor bleeding. | At Baseline and 120 Minutes | 
| Systolic Blood Pressure |  | At Baseline, 12 minutes, and 120 minutes | 
| Diastolic Blood Pressure |  | At Baseline, 12 minutes, and 120 minutes | 
| Heart Rate |  | At Baseline, 12 minutes, and 120 minutes | 
| Oxygen Saturation |  | At Baseline, 12 minutes, and 120 minutes | 
| Number of Participants With Adverse Events by Dose Level and Age |  | from baseline to 24 hours following drug administration | 
| Incidence of Adverse Events by Dose Level Regardless of Age |  | from baseline to 24 hours 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