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

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).

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.