Four Arm Safety & Efficacy With Antipyrine and Benzocaine Otic Solution in Children With Acute Otitis Media

Study Overview
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Brief Summary
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The primary objective is to compare the effect of treatment with a combination of ear solutions on the reduction of pain symptoms at 1 hour after dosing in children with acute otitis media.

Detailed Description
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Reduction of pain symptoms will be measured by using the Face, Legs, Activity, Cry, Consolability Scale (FLACC) and the Faces pain Scale Revised (FPS-R).

Official Title
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A Four-arm, Randomized, Double-blind, Active and Placebo Controlled Study to Determine the Safety and Efficacy of a Combination Antipyrine and Benzocaine Otic Solution Compared With Antipyrine Otic Solution Alone, Benzocaine Otic Solution Alone and to Placebo Otic Solution to Relieve Pain Symptoms in Children With Acute Otitis Media.

Conditions
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Acute Otitis Media

Intervention / Treatment
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* Drug: Antipyrine and Benzocaine otic solution
* Drug: Antipyrine Otic Solution
* Drug: Benzocaine Otic Solution
* Drug: Placebo Otic solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical Diagnosis of Acute Otitis Media Moderate to severe pain Normally active and in good health as determined by the PI Parent or legal guardian consent Caregiver available to complete diaries during study Exclusion Criteria: History of or current Perforated tympanic membrane Tympanostomy tubes Acute or chronic otitis externa seborrheic dermatitis Received any otic topical or systemic antibiotic within 14 days of enrollment Receiving medication on a chronic basis for pain Known hypersensitivity to investigational product. clinical significant mental illness as determined by the PI Exposed to another investigational agent within 30 days before study entry. Any condition the PI believed will interfere with the ability to comply with all study procedures History of glucose 6-phosphate dehydrogenase deficiency History or currently anemic Congenital methemoglobinemia Recent history of acute gastroenteritis within 14 days of enrollment

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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antipyrine and Benzocaine Otic solution<br>antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping | Drug: Antipyrine and Benzocaine otic solution<br>* antipyrine 54 mg and benzocaine 14 mg<br>Drug: Placebo Otic solution<br>* Placebo otic solution will be glycerin that is dehydrated<br>|
| Active Comparator: Antipyrine Otic Solution<br>Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping | Drug: Antipyrine Otic Solution<br>* Antipyrine 54 mg and glycerine dehydrated to 1.0 mL<br>Drug: Placebo Otic solution<br>* Placebo otic solution will be glycerin that is dehydrated<br>|
| Active Comparator: Benzocaine Otic Solution<br>benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping | Drug: Benzocaine Otic Solution<br>* benzocaine 14 mg and glycerine dehydrated to 1.0 mL<br>Drug: Placebo Otic solution<br>* Placebo otic solution will be glycerin that is dehydrated<br>|
| Placebo Comparator: Placebo<br>Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping | Drug: Placebo Otic solution<br>* Placebo otic solution will be glycerin that is dehydrated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) | The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Baseline and 1 hour after a single dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R)15 Min Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 15 min post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 30 Min Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 30 min post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 3 Hour Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 3 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 6 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 6 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 12 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 12 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 24 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 24 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 36 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 36 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 48 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 48 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 60 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 60 hour post first dose | 
| Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 72 Hours Post First Dose | The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose. The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain. | Change from Baseline to 72 hour post first dose |