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.

Study Overview

• Status: Completed
• Conditions: Acute Otitis Externa
• Intervention / Treatment: Drug: Ciprodex®; Drug: EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Cidra, Puerto Rico, 00739
    • Advance Medical Concepts, PSC
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Birmingham Pediatric Associates
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Desert Clinical Research/Clinical Research Advantage, Inc.
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Children's Clinic of Jonesboro, PA
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • California
    • Anaheim, California, United States, 92804
      • Southland Clinical Research Center
    • Bellflower, California, United States, 90706
      • Southland Clinical Reseach Center
    • Beverly Hills, California, United States, 90212
      • Alessi Institute
    • Buena Park, California, United States, 90620
      • American Clinical Trials
    • Los Angeles, California, United States, 90017
      • Mcs Clinical Trials
    • Sacramento, California, United States, 95815
      • Sacramento Ear, Nose and Throat Surgical and Medical Group, Inc
    • Sacramento, California, United States, 95822
      • Benchmark Research
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Clinix Health Services of Colorado/Clinical Research Advantage, Inc.
    • Colorado Springs, Colorado, United States, 80909
      • Colorado ENT & Allergy
    • Colorado Springs, Colorado, United States, 80920
      • Colorado Springs Health Partners/Clinical Research Advantage, Inc.
  • Florida
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Medical Center
    • Hialeah, Florida, United States, 33012
      • Palm Springs Research Institute
    • Miami, Florida, United States, 33165
      • Abel & Buchheim PR, Inc.
    • Miami, Florida, United States, 33165
      • Integrity Clinical Trials, LLC
  • Georgia
    • Marietta, Georgia, United States, 30062
      • Pediatrics & Adolescent Medicine, PA
    • Marietta, Georgia, United States, 30067
      • Urban Family Practice/Clinical Research Advantage
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas, LLC
  • Louisiana
    • Eunice, Louisiana, United States, 70535
      • Horizon Research Group, LLC
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
      • Woburn Pediatric Associates
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Pioneer Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center for Nevada, LLC
  • New Jersey
    • Morganville, New Jersey, United States, 07751
      • ProMetrix Clinical Studies
    • Whitehouse Station, New Jersey, United States, 08889
      • Whitehouse Station Family Medicine
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Asheboro Research Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Ear, Nose, and Throat Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
    • Houston, Texas, United States, 77025
      • Gulf Coast Medical Research
    • Missouri City, Texas, United States, 77459
      • Gulf Coast Medical Research
    • San Angelo, Texas, United States, 76904
      • Benchmark Research
    • Splendora, Texas, United States, 77372
      • Mercury Clinical Research, Inc
    • Sugar Land, Texas, United States, 77478
      • Gulf Coast Medical Research
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research & Development
    • Saint George, Utah, United States, 84790
      • Chyrsalis Clinical Research
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research/First Med East
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research/Foothill Family Clinic South
  • Virginia
    • Burke, Virginia, United States, 22015
      • PI-Coor Clinical Research, LLC
    • Charlottesville, Virginia, United States, 22902
      • Pediatric Research of Charlottesville, LLC
    • Midlothian, Virginia, United States, 23113
      • Heugenot Pediatrics, PC
  • Washington
    • Richland, Washington, United States, 97030
      • Zain Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Safety outcomes evaluated; AEs	Each monitoring visit through 15 +/- 1 days

Collaborators and Investigators

• Sponsor: Exela Pharma Sciences, LLC.
• Investigators: Study Chair: Michael H Silverman, MD, BioStrategics Consulting Ltd

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2014
• Primary Completion (Actual): August 11, 2015
• Study Completion (Actual): August 11, 2015

Study Registration Dates

• First Submitted: August 11, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis Externa; Otitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Ciprofloxacin
• Other Study ID Numbers: EXL CDOS-300 AOE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No