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

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

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01710787

Enrollment

110

Registered

2012-10-19

Start date

2012-10-31

Completion date

2013-02-28

Last updated

2017-08-30

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. The intent is to treat 110 subjects, with enrollment balanced evenly between the 2 study sites, 2:2:1 randomization within each study site and an overall goal of 44 subjects treated with Kovacaine Mist, 44 treated with Tetracaine alone, and 22 treated with Placebo. Recruitment will be from diverse dental patient populations.

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	Description
Number of Participants Who Completed the Study Dental Procedure After Without Need for Rescue by Injection of Local Anesthetic.	at 15 minutes with a 3 minute window	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.

Secondary

Measure	Time frame	Description
Number of Participants With a Heart Rate Lower Than 50 Bpm	at any time within 120 minutes following drug administration	—
Intraoral Soft-tissue Anesthesia (Yes/no)	at Baseline, 15, 30, 45, 60, 90, and 120 minutes with a 3 minute window	Number of patients who reported no pain when incisive papilla soft-tissue was tested with a probe at designated timepoints
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	—
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 105 mm Hg	at any time within 120 minutes following drug administration	—
Number of Participants With a Decrease From Baseline in Diastolic Blood Pressure Greater Than or Equal to 10 mm Hg and to a Value Lower Than 50 mm Hg	at any time within 120 minutes following drug administration	—
Absolute Maximum Change From Baseline in Heart Rate	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	—
Absolute Maximum Change From Baseline in 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	—
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	—
Alcohol Sniff Test	administered at baseline, 120 minutes and approximately 24 hours after drug administration	The distance from the nose (in centimeters) that a patient is able to detect the smell of alcohol on an alcohol swab.
Intraoral Soft-tissue Anesthesia (Onset and Duration)	up to 120 mins post-dose	Mean onset and duration of incisive papilla anesthesia based on number of patients who reported no pain when soft-tissue was tested with a probe at designated timepoints
Absolute Maximum Change From Baseline in Systolic Blood Pressure	from baseline to 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	44
Tetracaine Only, 3 Sprays Unilateral Tetracaine HCl 3% Tetracaine HCl 3%: 3 unilateral intranasal sprays per dose	44
Placebo, 3 Sprays Unilateral Placebo Placebo: 3 unilateral intranasal sprays per dose	22
Total	110

Baseline characteristics

Characteristic	Kovacaine Mist, 3 Sprays Unilateral	Tetracaine Only, 3 Sprays Unilateral	Placebo, 3 Sprays Unilateral	Total
Age, Continuous	37.1 years STANDARD_DEVIATION 14.73	31.3 years STANDARD_DEVIATION 12.01	35.7 years STANDARD_DEVIATION 14.64	34.5 years STANDARD_DEVIATION 13.82
Sex: Female, Male Female	30 Participants	16 Participants	12 Participants	58 Participants
Sex: Female, Male Male	14 Participants	28 Participants	10 Participants	52 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	42 / 44	44 / 44	11 / 22
serious Total, serious adverse events	0 / 44	1 / 44	0 / 22

Outcome results

Primary

Number of Participants Who Completed the Study Dental Procedure After 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.

Time frame: at 15 minutes with a 3 minute window

Arm	Measure	Value (NUMBER)
Kovacaine Mist, 3 Sprays Unilateral	Number of Participants Who Completed the Study Dental Procedure After Without Need for Rescue by Injection of Local Anesthetic.	84.1 percentage of patients
Tetracaine Only, 3 Sprays Unilateral	Number of Participants Who Completed the Study Dental Procedure After Without Need for Rescue by Injection of Local Anesthetic.	27.3 percentage of patients
Placebo, 3 Sprays Unilateral	Number of Participants Who Completed the Study Dental Procedure After Without Need for Rescue by Injection of Local Anesthetic.	27.3 percentage of patients

Secondary

Absolute Maximum Change From Baseline in Diastolic Blood Pressure

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 Diastolic Blood Pressure	10.5 mmHg	Standard Deviation 7.12
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Diastolic Blood Pressure	7.3 mmHg	Standard Deviation 4.96
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Diastolic Blood Pressure	6.7 mmHg	Standard Deviation 4.91

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	9.4 bpm	Standard Deviation 11.53
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Heart Rate	10.5 bpm	Standard Deviation 10.74
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Heart Rate	7.0 bpm	Standard Deviation 7.97

Secondary

Absolute Maximum Change From Baseline in Systolic Blood Pressure

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 Systolic Blood Pressure	13.7 mm Hg	Standard Deviation 10.74
Tetracaine Only, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure	10.8 mm Hg	Standard Deviation 9.15
Placebo, 3 Sprays Unilateral	Absolute Maximum Change From Baseline in Systolic Blood Pressure	5.1 mm Hg	Standard Deviation 9.32

Secondary

Alcohol Sniff Test

The distance from the nose (in centimeters) that a patient is able to detect the smell of alcohol on an alcohol swab.

Time frame: administered at baseline, 120 minutes and approximately 24 hours after drug administration

Arm	Measure	Group	Value (MEAN)	Dispersion
Kovacaine Mist, 3 Sprays Unilateral	Alcohol Sniff Test	120 Minutes	18 cm	Standard Deviation 9.47
Kovacaine Mist, 3 Sprays Unilateral	Alcohol Sniff Test	Pre-Study (Baseline)	19.2 cm	Standard Deviation 8.96
Kovacaine Mist, 3 Sprays Unilateral	Alcohol Sniff Test	24 Hours	18.2 cm	Standard Deviation 8.51
Tetracaine Only, 3 Sprays Unilateral	Alcohol Sniff Test	120 Minutes	17.7 cm	Standard Deviation 9.48
Tetracaine Only, 3 Sprays Unilateral	Alcohol Sniff Test	Pre-Study (Baseline)	18.8 cm	Standard Deviation 10
Tetracaine Only, 3 Sprays Unilateral	Alcohol Sniff Test	24 Hours	16.1 cm	Standard Deviation 8.74
Placebo, 3 Sprays Unilateral	Alcohol Sniff Test	Pre-Study (Baseline)	21.2 cm	Standard Deviation 8.35
Placebo, 3 Sprays Unilateral	Alcohol Sniff Test	24 Hours	20.4 cm	Standard Deviation 8.38
Placebo, 3 Sprays Unilateral	Alcohol Sniff Test	120 Minutes	20.9 cm	Standard Deviation 8.13

Secondary

Intraoral Soft-tissue Anesthesia (Onset and Duration)

Mean onset and duration of incisive papilla anesthesia based on number of patients who reported no pain when soft-tissue was tested with a probe at designated timepoints

Time frame: up to 120 mins post-dose

Population: The analysis population includes patients who received a rescue injection of local anesthetic. Local anesthetic may cause soft-tissue anesthesia, impacting this endpoint. In addition, only patients from one site (out of the two sites for the study) are used for this analysis. The other site administered this assessment incorrectly.

Arm	Measure	Group	Value (MEAN)	Dispersion
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Onset	9.7 minutes	Standard Deviation 7.5
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Duration	79.2 minutes	Standard Deviation 27
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Onset	19.5 minutes	Standard Deviation 17.6
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Duration	32.1 minutes	Standard Deviation 15.2
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Onset	37.0 minutes	Standard Deviation 0
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Onset and Duration)	Duration	26.0 minutes	Standard Deviation 17.3

Secondary

Intraoral Soft-tissue Anesthesia (Yes/no)

Number of patients who reported no pain when incisive papilla soft-tissue was tested with a probe at designated timepoints

Time frame: at Baseline, 15, 30, 45, 60, 90, and 120 minutes with a 3 minute window

Population: Only patients from one site (out of the two sites for the study) are used for this analysis. The other site administered this assessment incorrectly.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	120 mins	5 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	60 mins	17 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	45 mins	21 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	15 mins	19 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Baseline	0 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	90 mins	10 Participants
Kovacaine Mist, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	30 mins	17 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	45 mins	5 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Baseline	0 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	15 mins	8 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	30 mins	3 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	60 mins	2 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	90 mins	1 Participants
Tetracaine Only, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	120 mins	0 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	60 mins	1 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	15 mins	0 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	120 mins	0 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	90 mins	0 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	45 mins	3 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	30 mins	0 Participants
Placebo, 3 Sprays Unilateral	Intraoral Soft-tissue Anesthesia (Yes/no)	Baseline	0 Participants

Secondary