Acute Otitis Externa
Conditions
Keywords
Acute Otitis Externa
Brief summary
The purpose of this study was to demonstrate the superiority of AL-60371, 0.3% Otic Suspension relative to AL-60371 Vehicle based on clinical cures at test-of-cure (TOC) for the treatment of acute otitis externa (AOE).
Detailed description
Patients were evaluated for safety and efficacy during the visits conducted at Day 3 (on-therapy), Day 8 (end-of-therapy), and Day 11 (TOC). Patients or parents/legal guardians completed a telephone diary twice daily to record assessments of ear pain, ear pain medication use, and the impact of ear pain on sleep and other daily activities.
Interventions
OTHERAL-60371 Vehicle
Inactive ingredients used as a placebo comparator
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 6 months of age. * Clinical diagnosis of acute otitis externa (AOE) based on clinical observation and of presumed bacterial origin in at least one ear. * Combined numerical score of ≥4 in at least one affected ear at the Day 1 exam for tenderness, erythema, and edema. * Agree to refrain from water immersion of the ears during the conduct of the entire study. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Duration of signs or symptoms of AOE greater than 28 days in the affected ear(s) as reported by patient or parent/guardian. * Presence of a tympanostomy tube or perforated tympanic membrane in the affected ear(s). * Clinically diagnosed otic disease other than AOE (eg, malignant otitis externa) in the affected ear(s). * Known or suspected ear infection of yeast, fungal or mycobacterial origin in the affected ear(s). * Prior otologic surgery within 6 months of study entry in the affected ear(s). * Known or suspected allergy or hypersensitivity to quinolones or other ingredients present in the medications to be used in the study. * Patients who use ear plugs, head phones or ear buds and are unwilling to discontinue their use during the study period. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Clinical Cures at the Day 11 (TOC) Visit | Day 11 | An otoscopic exam was conducted by the physician. Clinical cure was considered attained if the sum of the numerical scores of the 3 signs and symptoms of AOE (tenderness, erythema, and edema) was 0 at Day 11. In this analysis, the clinical cure outcome at Day 11 (TOC) was considered a failure for all pathogen positive patients who did not complete the study (for any reason). Proportion of patients is reported as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Microbiological Successes at the Day 11 (TOC) Visit | Day 11 | Microbiological success was considered attained if all pretherapy bacteria were absent from the exit otic specimen. The presence of fungi and/or yeast was not considered in the determination of microbiological success. In this analysis, the microbiological success value at Day 11 (TOC) was considered a failure for all pathogen positive patients who did not complete the study (for any reason). Proportion of patients is reported as a percentage. |
| Median Time to Cessation of Ear Pain as Reported by the Patient or Parent/Legal Guardian Via the Telephone Diary | Time to event, up to Day 11 | Cessation of ear pain was defined as occurring on the first time point that ear pain was absent (morning or evening) and did not return in any subsequent diary entries. Day 1 was the starting point for this time-to-event analysis. For this analysis, all patients who did not complete the study and ear pain never ceased had their ear pain considered as being present throughout the planned duration of the study. |
Participant flow
Recruitment details
Participants were recruited from 68 investigational centers located in the United States, Puerto Rico, and Canada.
Pre-assignment details
Of the 768 consented participants, 75 were exited from the study as screen failures prior to randomization. This reporting group includes all randomized participants (693).
Participants by arm
| Arm | Count |
|---|---|
| AL-60371 AL-60371, 0.3% Otic Suspension, 4 drops to the affected ear(s) twice daily for 7 days | 344 |
| Vehicle AL-60371 Vehicle, 4 drops to the affected ear(s) twice daily for 7 days | 342 |
| Total | 686 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 15 |
| Overall Study | BL Culture + for Group A Strep | 0 | 1 |
| Overall Study | BL Culture + for Yeast//Fungi | 0 | 1 |
| Overall Study | Did not use product | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Noncompliance | 0 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Randomized in Error | 2 | 4 |
| Overall Study | Stopped medication | 0 | 1 |
| Overall Study | Subj Decision Unrelated to Adverse Event | 4 | 3 |
| Overall Study | Treatment Failure | 33 | 66 |
Baseline characteristics
| Characteristic | AL-60371 | Total | Vehicle |
|---|---|---|---|
| Age, Customized Adolescents (12 to 17 years) | 64 participants | 106 participants | 42 participants |
| Age, Customized Adults (18 to 64 years) | 195 participants | 381 participants | 186 participants |
| Age, Customized Children (2 to 11 years) | 61 participants | 144 participants | 83 participants |
| Age, Customized Elderly (≥ 65 years) | 21 participants | 50 participants | 29 participants |
| Age, Customized Infants/Toddlers (18 days to 23 months) | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 202 Participants | 385 Participants | 183 Participants |
| Sex: Female, Male Male | 142 Participants | 301 Participants | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 344 | 0 / 342 |
| serious Total, serious adverse events | 0 / 344 | 1 / 342 |
Outcome results
Primary
Proportion of Patients With Clinical Cures at the Day 11 (TOC) Visit
An otoscopic exam was conducted by the physician. Clinical cure was considered attained if the sum of the numerical scores of the 3 signs and symptoms of AOE (tenderness, erythema, and edema) was 0 at Day 11. In this analysis, the clinical cure outcome at Day 11 (TOC) was considered a failure for all pathogen positive patients who did not complete the study (for any reason). Proportion of patients is reported as a percentage.
Time frame: Day 11
Population: This analysis population includes the pathogen positive participants of the intent-to-treat (ITT) analysis set, ie, all participants who received study medication and were pathogen positive in the study ear at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AL-60371 | Proportion of Patients With Clinical Cures at the Day 11 (TOC) Visit | 71.7 percentage of participants |
| Vehicle | Proportion of Patients With Clinical Cures at the Day 11 (TOC) Visit | 33.3 percentage of participants |
Secondary
Median Time to Cessation of Ear Pain as Reported by the Patient or Parent/Legal Guardian Via the Telephone Diary
Cessation of ear pain was defined as occurring on the first time point that ear pain was absent (morning or evening) and did not return in any subsequent diary entries. Day 1 was the starting point for this time-to-event analysis. For this analysis, all patients who did not complete the study and ear pain never ceased had their ear pain considered as being present throughout the planned duration of the study.
Time frame: Time to event, up to Day 11
Population: This analysis population includes the pathogen positive participants of the intent-to-treat (ITT) analysis set, ie, all participants who received study medication and were pathogen positive in the study ear at baseline. Patients who did not report ear pain at any diary entry during first 7 days of the study were excluded from the analysis.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AL-60371 | Median Time to Cessation of Ear Pain as Reported by the Patient or Parent/Legal Guardian Via the Telephone Diary | 4.0 days | Standard Error 0.2 |
| Vehicle | Median Time to Cessation of Ear Pain as Reported by the Patient or Parent/Legal Guardian Via the Telephone Diary | 7.0 days | Standard Error 0.4 |
Secondary
Proportion of Patients With Microbiological Successes at the Day 11 (TOC) Visit
Microbiological success was considered attained if all pretherapy bacteria were absent from the exit otic specimen. The presence of fungi and/or yeast was not considered in the determination of microbiological success. In this analysis, the microbiological success value at Day 11 (TOC) was considered a failure for all pathogen positive patients who did not complete the study (for any reason). Proportion of patients is reported as a percentage.
Time frame: Day 11
Population: This analysis population includes the pathogen positive participants of the intent-to-treat (ITT) analysis set, ie, all participants who received study medication and were pathogen positive in the study ear at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AL-60371 | Proportion of Patients With Microbiological Successes at the Day 11 (TOC) Visit | 66.9 percentage of participants |
| Vehicle | Proportion of Patients With Microbiological Successes at the Day 11 (TOC) Visit | 13.0 percentage of participants |