Dose-Ranging Study of Intranasal Kovacaine Mist in Pediatric Subjects

This is a single-center, open-label, randomized, parallel-groups, dose-ranging study to
assess the efficacy and safety of intranasally administered Kovacaine Mist for anesthetizing
maxillary teeth in pediatric subjects.

The study will employ an open-label design to determine the lowest effective doses (LEDs),
and assess the safety and efficacy of Kovacaine Mist administered intranasally for inducing
pulpal anesthesia of maxillary primary teeth numbers A to J and maxillary permanent teeth
numbers 4 to 13 (maxillary right second premolar to maxillary left second premolar)
sufficient to allow completion of the Study Dental Procedure, and will be carried out in
healthy children of either sex between the ages of 3 and 17 years, inclusive.

Inclusion Criteria:

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

- Need for an operative restorative dental procedure on a single vital maxillary
primary tooth (#A to J) or permanent tooth (#4 to13), other than a maxillary
permanent first, second or third molar, requiring local anesthesia with an expected
treatment duration not exceeding 60 minutes.

- 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.

- If age 8 and above, able to understand and provide informed assent.

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

- Patency of the naris ipsilateral to the tooth undergoing the Study Dental Procedure.

- Minimum weight: Subjects in Cohorts A and B (age 6 and above) must weigh at least
20kg (44 lb.). Subjects in Cohort C (age 3 and above) must weigh at least 10kg (22
lb.).

Exclusion Criteria:

- Dental care requiring a local anesthetic within the 24 hours prior to anticipated
study participation.

- 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 take a urine pregnancy test
on the day of, but prior to, study drug administration to rule out pregnancy.)

- Inadequately controlled thyroid disease of any type.

- Use of 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).

- Anticipated need for use of 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.

- Clinically relevant history of sinus/nasal surgery, recent epistaxis, nasal
congestion or sinus infections, or use of a "sinus medication" within the 48 hours
prior to anticipated study participation.

- History of alcoholism and/or drug abuse.

- Pulpal pathology in the index tooth.

- Anticipated need for use of nitrous oxide before or during the Study Dental
Procedure.

- Any chronic or currently uncontrolled psychogenic, neurological, endocrine,
pulmonary, cardiovascular, renal, gastrointestinal or hepatic disease or condition
with manifestations that might confound interpretation of study results or make
receipt of study medication a source of risk for adverse outcome.

- Fever defined as body temperature ≥100° (37°C) on the day of and prior to study drug
administration.