OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement

Study Overview
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Brief Summary
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The purpose of this study is to confirm the effectiveness, safety and tolerability of OTO-201 in the treatment of pediatric subjects with bilateral middle ear effusion who require tympanostomy tube placement.

Detailed Description
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This is a prospective, randomized, double-blind, sham-controlled, multicenter, Phase 3 study of OTO-201 administered intraoperatively in pediatric subjects with bilateral middle ear effusion requiring TT (tympanostomy tube) placement. One dose level (6 mg) of OTO-201 was evaluated relative to sham (empty syringe). Study subjects are required to have a clinical diagnosis of bilateral middle ear effusion requiring TT placement. On the day of surgery, prior to surgery, eligible subjects were examined via otoscope to confirm bilateral middle ear effusion. Subjects with bilateral middle ear effusion were randomized to either 6 mg OTO-201 or sham. Subjects without bilateral effusion on the day of surgery were not randomized and were considered screen failures. Approximately 264 subjects are planned to be randomized to OTO-201 or sham using a 2:1 allocation ratio. Randomization to OTO-201 or sham was stratified by age: 6 months to 2 years or >2 years. Subjects are to visit the study site for safety assessments and otoscopic examination on Days 4, 8, 15, and 29. The assessment of otorrhea by the blinded assessor for the primary efficacy endpoint occurred on Days 4, 8, and 15.

Official Title
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Prospective, Randomized, Double-Blind, Sham-Controlled, Multicenter, P3 Study of OTO-201 Given as a Single IT Injection For Intra-Operative Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement

Conditions
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Otitis Media With Effusion

Intervention / Treatment
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* Drug: OTO-201
* Drug: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria includes, but is not limited to: Subject is a male or female aged 6 months to 17 years, inclusive Subject has a clinical diagnosis of bilateral middle ear effusion requiring tympanostomy tube placement Subject's caregiver is willing to comply with the protocol and attend all study visits Exclusion Criteria includes, but is not limited to: Subject has a history of prior ear or mastoid surgery, not including myringotomy or myringotomy with tympanostomy tube placement Subject has a history of sensorineural hearing loss Subject has a history of chronic or recurrent bacterial infections other than otitis media that likely will require treatment with antibiotics during the course of the study

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OTO-201<br>OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery. | Drug: OTO-201<br>* Single, intratympanic injection<br>|
| Sham Comparator: Sham<br>Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery. | Drug: Sham<br>* Simulated single, intratympanic injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Treatment Failures. | Cumulative proportion of treatment failures: The efficacy endpoint for both trials was the cumulative proportion of study treatment failures through Day 15, defined as the occurrence of any of the following events: otorrhea as determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason any time post-surgery, as well as patients who missed visits or were lost-to-follow-up. | Day 15 - 2 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Safety variables included the frequency of adverse events (AEs) and results from otoscopic examinations, tympanometry, audiometry measurements. | Up to one month | 
| Microbiological Response | Subjects whose samples tested positive for bacteria in either or both ears at baseline with documented eradication or presumed eradication post-baseline. | Day 15 - 2 weeks after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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otitis media, otorrhea, middle ear effusion, tympanostomy tubes