Acute Otitis Media
Conditions
Keywords
AOMT, tympanostomy tubes, Otorrhea, anti-infective
Brief summary
The purpose of this study is to evaluate a single application of AL-60371/AL-817 Otic Suspension relative to ototopical CIPRODEX for sustained clinical cure, microbiological success, and time to cessation of otorrhea.
Detailed description
The results at the time of the interim analysis met the futility criteria and the study was subsequently stopped.
Interventions
DRUGAL-60371/AL-817 otic suspension
DRUGCiprofloxacin 0.3%/dexamethasone 0.1% otic suspension
CIPRODEX®
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
* Parent or guardian: Read and sign the informed consent. When required by the Institutional Review Board, child must agree to sign an approved assent form; * Presence of otorrhea (visible by parent or guardian) of 21 days or less in duration; * Presence of patent tympanostomy tubes; * Refrain from water immersion of the ears following surgery without the use of adequate ear protection during swimming, bathing, showering and other water-related activities; * Parent or guardian: Agree to comply with the requirements of the study, administer the study medication as directed, complete required study visits, and comply with the protocol; * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* NOT otorrhea-free for at least seven days following tympanostomy tube surgery; * Menarcheal females; * Previous otologic surgery, except tympanic membrane, within one year of study entry; * History of/or current acute or chronic non-tube otorrhea (through existing perforation of the eardrum); * Current acute otitis externa, malignant otitis externa, or other conditions which could interfere with evaluation of the study drug; * Diabetic (controlled or uncontrolled); * Use of prohibited medications; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Sustained Clinical Cure at Day 3 Visit | Day 3 post-treatment up to Day 8 or Early Exit | A sustained clinical cure at Day 3 was attained if otorrhea was absent at the Day 3 visit and continued to be absent through the last study visit (Day 8 or Early Exit). Proportion of subjects is reported as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Microbiological Success at the Day 8 Visit | Day 8 | Microbiological success was attained if all pre-therapy bacteria were absent in the Day 8 specimen. In a subject with no otorrhea at Day 8, eradication of pre-therapy bacteria was presumed and the subject was considered a microbiological success. |
| Median Time (in Days) to Cessation of Otorrhea | Time to event, up to Day 8 | Median time (in days) to the cessation of otorrhea (ie, otorrhea was absent) was calculated as the number of days from the Day 1 (Visit 1) to the absence of otorrhea in the affected ear(s) as recorded by the parent/guardian via the twice-daily diary. Cessation of otorrhea was defined as ending on the first day that otorrhea was absent from the affected ear(s) and remained absent for any/all subsequent diary entries. |
Participant flow
Recruitment details
Subjects were recruited from 12 study centers located in the US.
Pre-assignment details
Of the 84 enrolled, 14 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (70).
Participants by arm
| Arm | Count |
|---|---|
| AL-60371/AL-817 200 μL in affected ear(s) through tympanostomy tube on Day 1 (Visit 1) | 44 |
| CIPRODEX Four drops in affected ear(s) twice daily through tympanostomy tube for 7 days | 24 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Adverse Event (pre-treatment) | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Randomization Error | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | AL-60371/AL-817 | CIPRODEX | Total |
|---|---|---|---|
| Age, Continuous | 2.9 years STANDARD_DEVIATION 2.6 | 2.4 years STANDARD_DEVIATION 1.54 | 2.7 years STANDARD_DEVIATION 2.28 |
| Sex: Female, Male Female | 21 Participants | 9 Participants | 30 Participants |
| Sex: Female, Male Male | 23 Participants | 15 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 84 | 3 / 44 | 1 / 24 |
| serious Total, serious adverse events | 0 / 84 | 0 / 44 | 0 / 24 |
Outcome results
Primary
Proportion of Subjects With Sustained Clinical Cure at Day 3 Visit
A sustained clinical cure at Day 3 was attained if otorrhea was absent at the Day 3 visit and continued to be absent through the last study visit (Day 8 or Early Exit). Proportion of subjects is reported as a percentage.
Time frame: Day 3 post-treatment up to Day 8 or Early Exit
Population: This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AL-60371/AL-817 | Proportion of Subjects With Sustained Clinical Cure at Day 3 Visit | 38.5 percentage of subjects |
| CIPRODEX | Proportion of Subjects With Sustained Clinical Cure at Day 3 Visit | 31.8 percentage of subjects |
Secondary
Median Time (in Days) to Cessation of Otorrhea
Median time (in days) to the cessation of otorrhea (ie, otorrhea was absent) was calculated as the number of days from the Day 1 (Visit 1) to the absence of otorrhea in the affected ear(s) as recorded by the parent/guardian via the twice-daily diary. Cessation of otorrhea was defined as ending on the first day that otorrhea was absent from the affected ear(s) and remained absent for any/all subsequent diary entries.
Time frame: Time to event, up to Day 8
Population: This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AL-60371/AL-817 | Median Time (in Days) to Cessation of Otorrhea | NA days |
| CIPRODEX | Median Time (in Days) to Cessation of Otorrhea | NA days |
Secondary
Proportion of Subjects With Microbiological Success at the Day 8 Visit
Microbiological success was attained if all pre-therapy bacteria were absent in the Day 8 specimen. In a subject with no otorrhea at Day 8, eradication of pre-therapy bacteria was presumed and the subject was considered a microbiological success.
Time frame: Day 8
Population: This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AL-60371/AL-817 | Proportion of Subjects With Microbiological Success at the Day 8 Visit | NA percentage of subjects |
| CIPRODEX | Proportion of Subjects With Microbiological Success at the Day 8 Visit | NA percentage of subjects |