Comparative Efficacy and Safety of Ciprofloxacin 0.3% and Dexamethasone 0.1% in Acute Otitis Externa

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the clinical therapeutic non-inferiority of EXL CDOS to commercially available Ciprofloxacin 0.3% and Dexamethasone 0.1% Sterile Otic Suspension (Ciprodex®, Alcon) in the treatment of acute otitis externa (AOE) when administered twice daily for 7 days.

Detailed Description
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This was a Phase 3, multicenter, randomized, double-blind, active-controlled, parallel-group study in adults and children (age 6 months and older) with a diagnosis of AOE with a 2-day screening period followed by a 2-week participation period. Subjects were administered study drug, EXL CDOS or RLD, 4 drops in the affected ear(s) BID for 7 days. The primary endpoint, the proportion of subjects with a clinical AOE score of 0, was measured at the TOC Visit on Day 15.

Official Title
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A Phase 3, Randomized, Double-Blind, Active-Controlled, Parallel-Group Study of the Comparative Efficacy and Safety of EXL CDOS in Subjects With Acute Otitis Externa

Conditions
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Acute Otitis Externa

Intervention / Treatment
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* Drug: Ciprodex®
* Drug: EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 6 months of age and over; Clinically documented AOE consistent with the diagnostic guidelines of the American Academy of Otolaryngology-Head and Neck Surgery Foundation in 1 or both ears; Inflammation and/or edema ≥2 on the AOE scale, and otorrhea and/or tenderness present; AOE of <4 weeks duration; Intact tympanic membrane(s) in the treated ear(s); Willingness to refrain from swimming through the TOC/ Visit 5; For subjects with AOE associated with hearing aid use, willingness to discontinue the use of hearing aid(s) in the affected ear(s) through the TOC/Visit 5; Ability to complete the study in compliance with the protocol; For adult subjects, ability to understand and provide written informed consent; and For pediatric subjects, a parent or legal guardian has provided written informed consent; and For children age 6 and above, ability to understand and provide assent according to institutional requirements. Exclusion Criteria: Acute or chronic suppurative otitis media; Post-tympanostomy tube acute otorrhea; Malignant otitis externa; Suspected or overt fungal or viral ear infection; Congenital abnormalities or obstructive bony exostoses of the external auditory canal of the treated ear(s); Seborrheic dermatitis or other dermatologic conditions of the external auditory canal of the treated ear(s) which could confound evaluation; Mastoiditis or other suppurative infectious or non-infectious disorders of the treated ear(s); Malignant tumors of the external auditory canal of the treated ear(s); History of otologic surgery of the treated ear(s), with the exception of tympanic membrane surgery >6 months prior to Baseline; Four or more episodes of otitis externa (OE) in the previous year; Uncontrolled diabetes mellitus; Immunosuppressive disorder, including known Human Immunodeficiency Virus infection; Renal insufficiency; Hepatitis or hepatic insufficiency; Receipt of systemic antibiotic concurrently or within 72 hours prior to Baseline; Receipt of topical otic antibiotic within 24 hours prior to Baseline; Use of systemic corticosteroid concurrently or within 30 days prior to Baseline; Use of topical otic corticosteroids concurrently or within 7 days prior to Baseline; Concurrent use of systemic or topical otic nonsteroidal or other anti-inflammatory drugs; Use of topical vinegar, alcohol, or other astringent otic preparations concurrently or within 24 hours prior to Baseline; Pregnancy, planned pregnancy, or lactation; Known sensitivity or intolerance to quinolone antibacterial agents; Previous participation in this trial; Participation in another investigational drug or vaccine trial concurrently or within 30 days; or Significant acute or chronic medical, neurologic, or psychiatric illness in the subject or parent/guardian that, in the judgment of the Principal Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

Ages Eligible for Study
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Minimum Age: 6 Months

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ciprodex®, RLD<br>Ciprodex®, Otic Suspension, Twice daily for 7 days | Drug: Ciprodex®<br>* Treatment of acute otitis externa (AOE) when administered twice daily for 7 days<br>|
| Experimental: EXL CDOS<br>EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days | Drug: EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension<br>* Treatment of acute otitis externa (AOE) when administered twice daily for 7 days<br>* Other names: Ciprofloxacin 0.3% and Dexamethasone 0.1% Sterile Otic Suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Cure of AOE | The primary efficacy endpoint was the clinical cure of AOE, defined as the proportion of subjects with a clinical AOE score of 0 at the TOC Visit. Subjects with AOE in both ears were considered to have achieved clinical cure of AOE if the clinical AOE score was 0 for both ears. The clinical AOE score was defined as the sum of scores for inflammation and edema (0=absent, 1=mild, 2=moderate, 3=severe) and tenderness and otorrhea (0=absent, 1=present). | 7 days after the completion of therapy; at Day 15 (+/- 1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Microbiological Cure (MC) | The secondary efficacy endpoint was the microbiological cure of AOE, defined as the proportion of subjects with microbiological cure at the TOC Visit. Subjects with AOE in both ears were considered to have achieved microbiological cure if microbiological cure was achieved in both ears. | 7 days after the completion of therapy; at Day 15 (+/- 1 day) |