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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01660893

Enrollment

Registered

2012-08-09

Start date

2012-08-31

Completion date

2012-09-30

Last updated

2017-09-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia

Keywords

operative, dental procedure

Brief summary

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

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.

Interventions

DRUGTetracaine HCl 3% and oxymetazoline HCl 0.05%

3 unilateral intranasal sprays per dose

DRUGTetracaine HCl 3%

3 unilateral intranasal sprays per dose

DRUGPlacebo

3 unilateral intranasal sprays per dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	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

Measure	Time frame	Description
Absolute Maximum Change From Baseline in Heart Rate	from baseline to 120 minutes following drug administration	—
Intraoral Soft-tissue Anesthesia (Yes/no)	at 15 minutes with a 3 minute window	Number of patients who reported no pain when incisive papilla and greater palatine foramen soft-tissue was tested with a probe
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	—
The Profile Over Time of Diastolic Blood Pressure	from baseline to 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	administered at approximately 24 hours after drug administration	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.
The Profile Over Time of Systolic Blood Pressure	from baseline to 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	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Kovacaine Mist, 3 Sprays Unilateral Tetracaine HCl 3% and oxymetazoline HCl 0.05% Tetracaine HCl 3% and oxymetazoline HCl 0.05%: 3 unilateral intranasal sprays per dose	10
Tetracaine Only, 3 Sprays Unilateral Tetracaine HCl 3% Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose	10
Placebo, 3 Sprays Unilateral Placebo Placebo: 3 unilateral intranasal sprays per dose	6
Total	26

Baseline characteristics

Characteristic	Kovacaine Mist, 3 Sprays Unilateral	Total	Placebo, 3 Sprays Unilateral	Tetracaine Only, 3 Sprays Unilateral
Age, Continuous	31.3 years STANDARD_DEVIATION 10.22	32.4 years STANDARD_DEVIATION 10.11	32.7 years STANDARD_DEVIATION 9.85	33.3 years STANDARD_DEVIATION 11.1
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants	24 Participants	6 Participants	9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	8 Participants	23 Participants	6 Participants	9 Participants
Region of Enrollment United States	10 participants	26 participants	6 participants	10 participants
Sex: Female, Male Female	8 Participants	20 Participants	4 Participants	8 Participants
Sex: Female, Male Male	2 Participants	6 Participants	2 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	9 / 10	10 / 10	6 / 6
serious Total, serious adverse events	0 / 10	0 / 10	0 / 6

Outcome results

Primary

Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).

Time frame: at 15 minutes with a 3 minute window

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Kovacaine Mist, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Success	5 Participants
Kovacaine Mist, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Failure	5 Participants
Tetracaine Only, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Success	2 Participants
Tetracaine Only, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Failure	8 Participants
Placebo, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Success	0 Participants
Placebo, 3 Sprays Unilateral	Completion of the Study Dental Procedure Without Need for Rescue by Injection of Local Anesthetic (Yes/no).	Failure	6 Participants

Secondary

Absolute Maximum Change From Baseline in Heart Rate

Time frame: from baseline to 120 minutes following drug administration

Arm	Measure	Value (MEAN)	Dispersion
Kovacaine Mist, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Heart Rate	3.4 bpm	Standard Deviation 8.62
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Heart Rate	3.5 bpm	Standard Deviation 7.09
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Heart Rate	2.3 bpm	Standard Deviation 7.55

Secondary

Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure

Time frame: from baseline to 120 minutes following drug administration

Arm	Measure	Group	Value (MEAN)	Dispersion
Kovacaine Mist, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Systolic Blood Pressure	12.8 mmHg	Standard Deviation 6.05
Kovacaine Mist, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Diastolic Blood Pressure	11.2 mmHg	Standard Deviation 5.35
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Systolic Blood Pressure	3.5 mmHg	Standard Deviation 8.34
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Diastolic Blood Pressure	4.5 mmHg	Standard Deviation 4.12
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Systolic Blood Pressure	1.2 mmHg	Standard Deviation 7.25
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	Diastolic Blood Pressure	6.2 mmHg	Standard Deviation 8.84

Secondary

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.

Time frame: administered at approximately 24 hours after drug administration

Arm	Measure	Value (MEAN)	Dispersion
Kovacaine Mist, 3 Sprays Unilateral	Alcohol Sniff Test	0.4 cm	Standard Deviation 5.44
Tetracaine Only, 3 Sprays Unilateral	Alcohol Sniff Test	0.8 cm	Standard Deviation 7.69
Placebo, 3 Sprays Unilateral	Alcohol Sniff Test	2.1 cm	Standard Deviation 2.94

Secondary

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

Time frame: at 15 minutes with a 3 minute window

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Incisive Papilla	7 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Greater Palatine Foramen	2 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Incisive Papilla	5 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Greater Palatine Foramen	1 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Incisive Papilla	2 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Greater Palatine Foramen	1 Participants

Secondary