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

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

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92350
      • Center for Dental Research Loma Linda University School
  • Maryland
    • Baltimore, Maryland, United States, 20740
      • University of Maryland, Baltimore
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, School of Dental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kovacaine Mist; 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%; The study drug is regional anesthetic delivered intranasally on the same side as the operative tooth; Other Names: Kovacaine Mist
Placebo Comparator: Placebo; Placebo - 2 sprays will be administered at the start of the procedure, if anesthesia is insufficient, a third spray will be administered.	Drug: Placebo; The placebo spray was identical in appearance to and was administered in the same volume and manner as the active ingredient.; Other Names: inactive ingredients

What is the study measuring?

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
The Profile Over Time of Heart Rate		from baseline to 120 minutes following 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
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 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 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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Received Three Sprays and Completed the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic.	A participant will receive two sprays and Study Dental Procedure will begin. If the participant does not have sufficient anesthesia a third sprays will be given. If after the third spray, the participant does not have sufficient anesthesia to complete the Study Dental Procedure, the participant is given a rescue injection of local anesthetic. This outcome analyzes just the participants who received the third spray and whether or not they completed the Study Dental Procedure without need for rescue by injection of local anesthesia.	at 25 minutes, +3 minute window

Collaborators and Investigators

• Sponsor: St. Renatus, LLC
• Collaborators: Rho, Inc.; Triligent International

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: operative; dental procedure
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Anesthetics, Local; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Phenylephrine; Oxymetazoline; Tetracaine
• Other Study ID Numbers: SR 3-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED