Acute Otitis Externa
Conditions
Brief summary
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
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.
Interventions
DRUGCiprodex®
Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
DRUGEXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension
Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Sponsors
Exela Pharma Sciences, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Cure of AOE | 7 days after the completion of therapy; at Day 15 (+/- 1 day) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microbiological Cure (MC) | 7 days after the completion of therapy; at Day 15 (+/- 1 day) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Each monitoring visit through 15 +/- 1 days | Safety outcomes evaluated * AEs |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ciprodex®, RLD Ciprodex®, Otic Suspension, Twice daily for 7 days
Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days | 254 |
| EXL CDOS EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days
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 | 245 |
| Total | 499 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Ciprodex®, RLD | Total | EXL CDOS |
|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 24.5 | 33.2 years STANDARD_DEVIATION 24.01 | 33.1 years STANDARD_DEVIATION 23.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 81 Participants | 166 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 173 Participants | 333 Participants | 160 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 42 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 233 Participants | 443 Participants | 210 Participants |
| Region of Enrollment Puerto Rico | 18 participants | 33 participants | 15 participants |
| Region of Enrollment United States | 236 participants | 466 participants | 230 participants |
| Sex: Female, Male Female | 132 Participants | 263 Participants | 131 Participants |
| Sex: Female, Male Male | 122 Participants | 236 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 47 / 247 | 42 / 252 |
| serious Total, serious adverse events | 0 / 247 | 1 / 252 |
Outcome results
Primary
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).
Time frame: 7 days after the completion of therapy; at Day 15 (+/- 1 day)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprodex®, RLD | Number of Participants With Clinical Cure of AOE | 190 Participants |
| EXL CDOS | Number of Participants With Clinical Cure of AOE | 191 Participants |
Secondary
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.
Time frame: 7 days after the completion of therapy; at Day 15 (+/- 1 day)
Population: The number of participants analyzed represents Bacteria-Positive cohort of subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprodex®, RLD | Number of Participants With Microbiological Cure (MC) | 115 Participants |
| EXL CDOS | Number of Participants With Microbiological Cure (MC) | 117 Participants |
Other Pre-specified
Number of Participants With Adverse Events
Safety outcomes evaluated * AEs
Time frame: Each monitoring visit through 15 +/- 1 days
Population: 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprodex®, RLD | Number of Participants With Adverse Events | 60 Participants |
| EXL CDOS | Number of Participants With Adverse Events | 67 Participants |