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

The study will employ a multi-center, randomized, double-blind, placebo-controlled,
parallel-groups design to demonstrate the safety and efficacy of Kovacaine Mist delivered
intranasally for inducing pulpal anesthesia of maxillary permanent teeth numbers 4 to 13
(maxillary right second premolar to maxillary left second premolar) or maxillary primary
teeth numbers A to J (maxillary right second primary molar to maxillary left second primary
molar) sufficient to allow completion of the Study Dental Procedure. The maxillary teeth
will be categorized in two subsets, anterior teeth (permanent teeth numbers 6 to 11 and
primary teeth numbers C to H) and posterior teeth (permanent teeth numbers 4, 5, 12, 13 and
primary teeth numbers A, B, I, J).

The intent is to treat 90 male and female subjects aged 3 to 17 years, inclusive, at 3 study
sites, 2:1 randomization within each study site, and an overall goal of 60 subjects treated
with Kovacaine Mist and 30 treated with placebo. Subjects will receive Kovacaine Mist or
placebo (2:1) according to the kit randomization plan within three dosing strata (100 µL,
200 µL or 400 µL) based on subject weight at entry: subjects weighing 10 to <20 kg, 20 to
<40 kg and ≥ 40 kg will be assigned to the 100 µL, 200 µL or 400 µL dose group,
respectively. Recruitment will be from diverse pediatric dental patient populations. To
ensure adequate representation in the 3 dose/weight groups, each stratum will contain at
least 25% of subjects.

Inclusion Criteria:

- Male or female 3-17 years of age inclusive.

- Need for an operative restorative dental procedure and requiring local anesthesia on
a single vital maxillary primary tooth (#A to J) or permanent tooth (#4 to13), with
no evidence of pulpal pathology.

- Normal lip, nose, eyelid, and cheek sensation.

- Accompanied and/or represented by a parent or guardian able to comprehend and sign
the informed consent document.

- Subject able to understand and provide assent to an age-appropriate subject assent
form (as defined by local practice or regulation).

- Patient or parent/guardian able to communicate with the investigator and comply with
the requirements of the protocol.

- Patency of the naris on the same side as the tooth undergoing the Study Dental
Procedure (the Study Treatment Tooth).

Exclusion Criteria:

- 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 lidocaine, 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 undergo urine testing on the
day of, but prior to, study drug administration to rule out pregnancy.)

- Inadequately controlled thyroid disease of any type.

- Having received any investigational drug (including Kovacaine Mist) and/or
participation in any clinical trial within 30 days of study participation.

- Frequent nose bleeds (≥ 5 per month).

- History of congenital or idiopathic methemoglobinemia.

- Presence of an upper respiratory infection and/or fever defined as body temperature
≥100.4° (38°C) on the day of and prior to study drug administration.