Study to Assess the Safety and Efficacy of Benzocaine for Pain Relief in Children Presenting With Acute Otitis Media

Study Overview
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Brief Summary
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To assess the clinical safety and efficacy of the Benzocaine relative to placebo in pain relief associated with acute otitis media.

Official Title
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Phase II, Multicenter, Double-Blind, Randomized, Vehicle-Controlled Study to Assess the Safety and Efficacy of Benzocaine for Pain Relief in Children Ages 2 Months to 12 Years Presenting With Acute Otitis Media

Conditions
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Pain, Acute Otitis Media

Intervention / Treatment
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* Drug: Benzocaine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ages 2 months to 12 years of age with a clinical diagnosis of AOM, and with ear pain (current episode <2 weeks duration). Baseline pain entry requires a minimum score of 4 on the FLACC or the FPS-R scale (depending on age) The patients must provide Institutional Review Board (IRB) approved written assent, as appropriate, which must be accompanied by an IRB approved written informed consent form (ICF) from the patient's legally acceptable representative (i.e., parent or guardian), as applicable. In addition, all patients or their legally acceptable representatives (i.e., parent or guardian) must sign a Health Insurance Portability and Accountability Act (HIPAA) authorization, if applicable Patients must be normally active and otherwise judged to be in good health on the basis of the medical history and a limited physical examination, as determined by the Investigator. Females of child bearing potential must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at Visit 1 Exclusion Criteria: Patients with bilateral AOM, 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 a Valsalva maneuver Patients who are subsequently diagnosed with a perforated membrane during treatment are to be discontinued immediately. Patients with indwelling tympanostomy tubes or draining otitis in the affected ear(s), bullous lesions, erythema of the tympanic membrane without other evidence of AOM, and patients with an anatomic defect of the ear or nasopharynx Complications of treated/untreated ear disease over the past 2 weeks Patients with comorbidity requiring antibiotic therapy, allergy to study medication, immunologic deficiency, and major medical condition(s). Patients with methemoglobinemia or a history of methemoglobinemia, vertigo, inherited enzyme deficiencies, impaired cardiac or respiratory functions, epilepsy, heart diseases, hypersensitivity, pyrogenic infection at or near the skin, inflamed or infected skin, dermatitis, shock, hepatic impairment, or myasthenia gravis Acute or chronic otitis externa Chronic otitis media (current episode ≥ 2 weeks) Patients who smoke are prohibited from participating in this study. Seborrheic dermatitis involving the affected external ear canal or pinna Any topical or systemic antibiotic received within the 14 days prior to study entry (topical antibiotics for acne will be allowed) Any topical drying agent or over-the-counter (OTC) therapy for otitis media received within 36 hours prior to enrollment Fever >102°F Known hypersensitivity to the study drug or similar compounds including any of the inactive ingredients Patients receiving medication on a chronic basis for pain (including steroidal or non-steroidal anti-inflammatory drugs) Use of ear drops or oral analgesics such as ibuprofen/acetaminophen within the 4 hours prior to study entry Use of sulfonamides, aminosalicylates, anti- cholinesterases, suxamethonium, antiarrhythmics, monoamine oxidase inhibitors, or tricyclic antidepressants Clinically significant mental illness (as determined by the Investigator) Exposure to any investigational agent within the 30 days prior to study entry Previous enrollment in this study Pregnant or lactating The child has a condition that the Investigator believes would interfere with the ability to provide assent (age appropriate) or comply with study instructions, or that might confound the interpretation of the study results, or put the child at undue risk

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benzocaine<br>Topical otic solution, every 1-2 hours, for up to 3 days | Drug: Benzocaine<br>* topical otic solution<br>|
| Placebo Comparator: Placebo<br>Topical otic solution, every 1-2 hours, for up to 3 days | Drug: Placebo<br>* topical otic solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed Pain Intensity Difference |  | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Difference |  | Up to 120 minutes | 
| Comparison of pain scores from AOM-SOS and FLACC pain measurement scales in patients 2 months to 4 years old |  | Up to 3 days | 
| Comparison of pain scores from VAS and FPS-R pain measurement scales in patients 5 years to 12 years old |  | Up to 3 days | 
| Physician Global Evaluation |  | Up to 3 days | 
| Evaluate dosing intervals with pain measurements assessed up to 120 minutes |  | Up to 120 minutes | 
| Report the onset of perceptible and meaningful pain relief using patient reports and stopwatch assessments | Patients will be given 2 stopwatches at the start of the study and instructed to stop one when they experience perceptible ('some') pain relief after the administration of the first dose (any change in pain intensity) and stop the other when they experience meaningful pain relief (a 'definite decrease in pain that makes them feel better') | Up to 120 minutes | 
| Assess the safety and tolerability of benzocaine | Safety will be assessed by adverse event reporting on all study days. Also, vital signs (blood pressure, pulse, temperature, and respiratory rate) and physical examinations will be assessed. | Up to 3 days |