Phase 3 Study to Compare the Efficacy and Safety of AR01 to a Placebo Solution for Relief of Pain in Acute Otitis Media

The study involves the initial clinic visit, using the ear drops at home and keeping a diary
about the ear pain experienced and medications taken. The patient will return to the clinic
4 days later for evaluation and to return the ear drops and diary. The clinic staff will
call to follow-up about the patient's condition seven days after the initial visit.

Inclusion Criteria:

- Subjects 2 mo. to < 19 yrs of age, with signs and symptoms of AOM, with moderate to
severe pain (current episode 2 wks duration). Moderate to severe pain is defined as a
score of 5 (on a scale of 0 - 10) on the FAECC pain scale as evaluated by a trained
clinical staff or 6 (on a scale of 0 - 10) on the FPS-R as evaluated by the subject.
Moderate to severe pain criteria must be met at eligibility and the pre-dose pain
assessment.

- Males or non-pregnant, non-lactating females.

- The subject's caregiver must have read and signed the written informed consent
(including assent from subjects 18 yrs as applicable according to Investigational
review board (IRB) guidelines) prior to study participation. Subjects 18 yrs old must
have read and signed the written informed consent prior to study participation.

- Normally active and otherwise judged to be in good health on the basis of medical
history and limited physical examination.

- Females of childbearing potential must have a urine pregnancy test at the
randomization visit with negative results returned prior to randomization.

Exclusion Criteria

- Perforated tympanic membrane, history of a perforated tympanic membrane in the last 6
months, or if a perforated tympanic membrane could not be ruled out by speculum
examination, impedance testing tympanometry, pneumatic otoscopy, or Valsalva
maneuver. Subjects who are subsequently diagnosed with a perforated membrane during
treatment are to be discontinued immediately. Subjects with tympanostomy tubes are
not allowed.

- Acute or chronic otitis externa.

- Chronic otitis media (refers to current episode 2 wks).

- Seborrheic dermatitis involving the affected external ear canal or pinna.

- Any otic, topical, or systemic antibiotic received within 14 days prior to study
entry (topical or systemic antibiotics for acne will be allowed on a chronic basis
for subjects who have been on a stable dose for at least 14 days prior to entry).

- Any topical drying agent or over-the-counter therapy for otitis media received within
36 hrs prior to enrollment.

- Known hypersensitivity to drug or similar compounds including any of the inactive
ingredients.

- Subjects receiving medication on a chronic basis for pain (including steroidal or
non-steroidal anti-inflammatory drugs) who have not been on a stable dose for at
least 1 month prior to entry into the study.

- Clinically significant mental illness that may interfere with the conduct of the
study (determined by Investigator).

- Exposure to any investigational agent within 30 days prior to study entry.

- Previous enrollment in this study.

- Subject/caregiver has a condition the Investigator believes would interfere with the
ability to provide consent or assent (age-appropriate) or comply with study
instructions, or that might confound the interpretation of the study results, or put
the subject at undue risk.

- Subject has a glucose 6-phosphate dehydrogenase deficiency or is taking concomitant
medications associated with methemoglobinemia (such as nitrates or nitrites; aniline
dyes; or medications, including lidocaine, prilocaine, phenazopyridine hydrochloride
[Pyridium], and others).

- Subject shows clinical signs of anemia. The absolute amount of deoxygenated or
abnormal hemoglobin (rather than its percentage) is required for cyanosis to be
clinically evident. Subjects with moderate-to-severe anemia may not appear cyanotic,
even with elevated percentages of deoxygenated or abnormal hemoglobins.

- Subject has congenital (i.e., hereditary) methemoglobinemia.

- Subject has a recent history of acute gastroenteritis within 14 days prior to study
entry.

- Subject exhibits clinical signs of methemoglobinemia, such as unexplained bluish
coloring of skin, fatigue, shortness of breath, failure to thrive, and headache.

- Subjects 5 to <19 yrs old who are unable to satisfactorily complete FPS-R screening
test.