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

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

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.

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.

Inclusion Criteria:

1. Male or female, 6 months of age and over;
2. Clinically documented AOE consistent with the diagnostic guidelines of the American Academy of Otolaryngology-Head and Neck Surgery Foundation in 1 or both ears;
3. Inflammation and/or edema ≥2 on the AOE scale, and otorrhea and/or tenderness present;
4. AOE of <4 weeks duration;
5. Intact tympanic membrane(s) in the treated ear(s);
6. Willingness to refrain from swimming through the TOC/ Visit 5;
7. 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;
8. Ability to complete the study in compliance with the protocol;
9. For adult subjects, ability to understand and provide written informed consent; and
10. For pediatric subjects, a parent or legal guardian has provided written informed consent; and
11. For children age 6 and above, ability to understand and provide assent according to institutional requirements.

Exclusion Criteria:

1. Acute or chronic suppurative otitis media;
2. Post-tympanostomy tube acute otorrhea;
3. Malignant otitis externa;
4. Suspected or overt fungal or viral ear infection;
5. Congenital abnormalities or obstructive bony exostoses of the external auditory canal of the treated ear(s);
6. Seborrheic dermatitis or other dermatologic conditions of the external auditory canal of the treated ear(s) which could confound evaluation;
7. Mastoiditis or other suppurative infectious or non-infectious disorders of the treated ear(s);
8. Malignant tumors of the external auditory canal of the treated ear(s);
9. History of otologic surgery of the treated ear(s), with the exception of tympanic membrane surgery >6 months prior to Baseline;
10. Four or more episodes of otitis externa (OE) in the previous year;
11. Uncontrolled diabetes mellitus;
12. Immunosuppressive disorder, including known Human Immunodeficiency Virus infection;
13. Renal insufficiency;
14. Hepatitis or hepatic insufficiency;
15. Receipt of systemic antibiotic concurrently or within 72 hours prior to Baseline;
16. Receipt of topical otic antibiotic within 24 hours prior to Baseline;
17. Use of systemic corticosteroid concurrently or within 30 days prior to Baseline;
18. Use of topical otic corticosteroids concurrently or within 7 days prior to Baseline;
19. Concurrent use of systemic or topical otic nonsteroidal or other anti-inflammatory drugs;
20. Use of topical vinegar, alcohol, or other astringent otic preparations concurrently or within 24 hours prior to Baseline;
21. Pregnancy, planned pregnancy, or lactation;
22. Known sensitivity or intolerance to quinolone antibacterial agents;
23. Previous participation in this trial;
24. Participation in another investigational drug or vaccine trial concurrently or within 30 days; or
25. 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.