Anesthesia
Conditions
Keywords
operative, dental procedure
Brief summary
The purpose of this study is to evaluate the efficacy of and recommended dosing regimen for unilateral administration of Kovacaine Mist in inducing pulpal anesthesia of the maxillary teeth for dental procedures.
Detailed description
This is a Phase II single-center, open-label clinical trial with three dosing regimens, designed to determine the efficacy and optimal dose of the Kovacaine Mist intranasal delivery system for inducing pulpal anesthesia of maxillary teeth numbers 4-13 (maxillary right second premolar to maxillary left second premolar). Kovacaine will be administered intranasally on the same side of the midline as the tooth on which the procedure will be performed in three dosing cohorts \[four 100 μL, two 200 μL, or one 200 μL spray(s)\] of 10 subjects each. The first cohort receiving 4 sprays will be completed before initiating study of the remaining two cohorts, which will be treated using a randomized, parallel-group design. Administration: Subjects in the 4- and 2-spray cohorts will be administered the same total dose of 12 mg tetracaine HCl/0.2 mg oxymetazoline HCl. The 4-spray cohort will be treated with a sequence of four 100-μL sprays at intervals of 4 minutes. The 2-spray cohort will be treated with a sequence of two 200 μL sprays 4 minutes apart. The 1-spray cohort will be administered one 200 μL spray, a total dose of 6 mg tetracaine HCl/0.1 mg oxymetazoline HCl, which is half the dose of the 2-spray cohort. Rescue: If the study drug does not provide sufficient anesthesia to allow for completion of the dental procedure, a rescue injection of articaine will be administered.
Interventions
DRUGKovacaine Mist 0.1 mL x 4 sprays
Dose = 4 intranasal sprays of study drug delivered at 4-minute intervals.
DRUGKovacaine Mist 0.2 mL x 2 sprays
Dose = 2 intranasal sprays of study drug delivered at 4-minute intervals.
DRUGKovacaine Mist 0.2 mL x 1 spray
Dose = 1 intranasal spray of study drug
Sponsors
Rho, Inc.
Triligent International
St. Renatus, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female subjects who are 18 years of age or older; * requiring an operative restorative procedure on a single maxillary tooth with no evidence of pulpal pathology requiring local anesthesia; * having normal lip, nose, eyelid, and cheek sensations; * able to understand and sign the informed consent document, communicate with the investigators, and understand and comply with the requirements of the protocol; * having patency of naris on same side of head as tooth requiring the dental procedure.
Exclusion criteria
* Inadequately controlled hypertension (blood pressures greater than 150/90) or untreated coronary heart disease; * inadequately controlled thyroid disease including Hashimoto's thyroiditis and partial thyroidectomy; * having frequent nose bleeds (10 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, benzocaine, other ester local anesthetics, or para-aminobenzoic acid (as found in PABA-containing sunscreens); * history of allergy or hypersensitivity to articaine, oxymetazoline, epinephrine, or sulfite preservatives; history of taking a monoamine oxidase inhibitor within the past 3 weeks; * are nursing, pregnant, suspected of being pregnant, or trying to become pregnant. (Females will be required to take a urine pregnancy test on the day of but prior to study drug administration to rule out pregnancy); * having used any investigational drug and/or participated in any clinical research trial within 30 days of baseline * enlarged prostate * narrow angle glaucoma * use of oxymetazoline or phenylephrine nasal spray or oral decongestant on the day of the study * congenital or idiopathic methemoglobinemia * diabetes mellitus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure | at 15 minutes, with +10 minute window |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | 60 minutes | — |
| The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | 60 minutes | — |
| Naris Examination | 60 minutes post drug administration | Number of patients with an abnormal naris examination finding. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Kovacaine Mist 0.1 mL x 4 Sprays Total dose: 12 mg tetracaine/0.2 mg oxymetazoline
Kovacaine Mist 0.1 mL x 4 sprays: Dose = 4 intranasal sprays of study drug delivered at 4-minute intervals. | 10 |
| Kovacaine Mist 0.2 mL x 2 Sprays Total dose: 12 mg tetracaine/0.2 mg oxymetazoline
Kovacaine Mist 0.2 mL x 2 sprays: Dose = 2 intranasal sprays of study drug delivered at 4-minute intervals. | 10 |
| Kovacaine Mist, 0.2 mL x 1 Spray Total dose: 6 mg tetracaine/0.1 mg oxymetazoline
Kovacaine Mist 0.2 mL x 1 spray: Dose = 1 intranasal spray of study drug | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Kovacaine Mist 0.2 mL x 2 Sprays | Kovacaine Mist, 0.2 mL x 1 Spray | Kovacaine Mist 0.1 mL x 4 Sprays | Total |
|---|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 9.55 | 54.0 years STANDARD_DEVIATION 15.2 | 51.5 years STANDARD_DEVIATION 12.42 | 54.7 years STANDARD_DEVIATION 12.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 6 Participants | 7 Participants | 7 Participants | 20 Participants |
| Gender Male | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 9 Participants | 29 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 | 10 / 10 | 9 / 10 | 8 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure
Time frame: at 15 minutes, with +10 minute window
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure | 10 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure | 7 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Receiving Kovacaine Mist Who do Not Require Rescue Anesthesia During the Operative Dental Procedure | 8 participants |
Secondary
Naris Examination
Number of patients with an abnormal naris examination finding.
Time frame: 60 minutes post drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Kovacaine Mist 0.1 mL x 4 Sprays | Naris Examination | 0 Participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | Naris Examination | 0 Participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | Naris Examination | 0 Participants |
Secondary
The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values.
Time frame: 60 minutes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kovacaine Mist 0.1 mL x 4 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased systolic BP >25% | 0 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased systolic BP >25% | 0 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased diastolic BP >25% | 0 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased diastolic BP >25% | 0 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased diastolic BP >25% | 0 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased systolic BP >25% | 1 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased diastolic BP >25% | 0 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased systolic BP >25% | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased diastolic BP >25% | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Decreased systolic BP >25% | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased diastolic BP >25% | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Incidence of Subjects Receiving Kovacaine Mist With Changes in Systolic and Diastolic Blood Pressure Exceeding +/- 25% of Preoperative Measurements Values. | Increased systolic BP >25% | 1 participants |
Secondary
The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed.
Time frame: 60 minutes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lip numb | 6 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lower eyelid numb | 3 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation in roof of mouth | 10 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Side of nose numb | 9 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Cheek numb | 6 participants |
| Kovacaine Mist 0.1 mL x 4 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation tapping front teeth | 10 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Cheek numb | 2 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation tapping front teeth | 8 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation in roof of mouth | 6 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lip numb | 5 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Side of nose numb | 5 participants |
| Kovacaine Mist 0.2 mL x 2 Sprays | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lower eyelid numb | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation in roof of mouth | 7 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Cheek numb | 1 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Side of nose numb | 5 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lower eyelid numb | 0 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Abnormal sensation tapping front teeth | 5 participants |
| Kovacaine Mist, 0.2 mL x 1 Spray | The Proportion of Subjects Giving a Positive Response to Evaluation Question for Subjective Numbness Assessment (SNA) After the Procedure is Completed. | Lip numb | 3 participants |