Otitis Media Recurrent, Otitis Media With Effusion in Children
Conditions
Brief summary
The purpose of this study is to evaluate EXE844 plus tympanostomy tubes compared to tympanostomy tubes only based on sustained clinical cure at end-of-therapy (EOT).
Interventions
PROCEDURETympanostomy Tube Insertion
Surgical procedure for treating pediatric cases of recurrent or chronic otitis media
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
* Recurrent acute otitis media (RAOM) or chronic otitis media with effusion (COME) and eligible for bilateral myringotomy and tympanostomy tube insertion. * Suspected bacterial infection at time of surgery in at least 1 ear. * Willing to 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. * Legally Authorized Representative (LAR) must read and sign the informed consent. * Parent or caregiver must agree to comply with the requirements of the study and administer study medication as directed, complete required study visits, and comply with the protocol. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Previous otologic or otologic-related surgery within the past 30 days or ongoing complications. * Middle ear pathology in either ear other than otitis media. * Current acute otitis externa (AOE), malignant otitis externa (MOE) or other conditions which could interfere with evaluation of the study drug. * Any systemic disease or disorder, complicating factor or structural abnormality that would negatively affect the conduct or outcome of the study based upon assessment by the Investigator. * Known or suspected allergy or hypersensitivity to quinolones or other active or inactive ingredients present in the medications to be used in the study. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Sustained Clinical Cure at Day 8 | Day 8 | A sustained clinical cure was attained if otorrhea was absent in the study ear at Day 8 (EOT) per the Investigator assessment and continued to be absent through the end of the study. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Microbiological Success at Day 14 | Day 14 | Microbiological success was attained if all pretherapy bacteria were absent in the study ear for the Test-of-Cure (TOC) (Day 14) specimen. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward). |
| Time to Cessation of Otorrhea | Up to Day 14 | Time (in days) to the cessation of otorrhea in the enrolled ear(s) was calculated as the number of days from the day of surgery to the absence of otorrhea (ie, no discharge) as reported by the parent/caregiver via the BID diary. Participants were considered a treatment failure if, at any time during the course of the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward). |
Participant flow
Recruitment details
Participants were recruited from 18 study centers located in the US and 2 study centers located in Canada.
Pre-assignment details
Of the 470 enrolled, 85 participants were exited as screen failures prior to randomization. This reporting group includes all randomized participants (385).
Participants by arm
| Arm | Count |
|---|---|
| EXE844 7 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 7 days after Tympanostomy Tube Insertion | 164 |
| EXE844 3 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion | 110 |
| Tubes Only Bilateral myringotomy and tympanostomy tube insertion | 111 |
| Total | 385 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Culture positive for yeast | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Randomized in error | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | EXE844 7 Days | EXE844 3 Days | Tubes Only | Total |
|---|---|---|---|---|
| Age, Continuous | 2.2 years STANDARD_DEVIATION 1.82 | 2.1 years STANDARD_DEVIATION 1.59 | 2.2 years STANDARD_DEVIATION 1.92 | 2.2 years STANDARD_DEVIATION 1.78 |
| Sex: Female, Male Female | 56 Participants | 45 Participants | 46 Participants | 147 Participants |
| Sex: Female, Male Male | 108 Participants | 65 Participants | 65 Participants | 238 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 470 | 0 / 164 | 0 / 110 | 0 / 111 |
| other Total, other adverse events | 7 / 470 | 27 / 164 | 21 / 110 | 40 / 111 |
| serious Total, serious adverse events | 1 / 470 | 1 / 164 | 1 / 110 | 0 / 111 |
Outcome results
Primary
Percentage of Subjects With Sustained Clinical Cure at Day 8
A sustained clinical cure was attained if otorrhea was absent in the study ear at Day 8 (EOT) per the Investigator assessment and continued to be absent through the end of the study. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).
Time frame: Day 8
Population: ITT analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EXE844 7 Days | Percentage of Subjects With Sustained Clinical Cure at Day 8 | 76.2 percentage of participants |
| EXE844 3 Days | Percentage of Subjects With Sustained Clinical Cure at Day 8 | 71.8 percentage of participants |
| Tubes Only | Percentage of Subjects With Sustained Clinical Cure at Day 8 | 56.8 percentage of participants |
Secondary
Percentage of Subjects With Microbiological Success at Day 14
Microbiological success was attained if all pretherapy bacteria were absent in the study ear for the Test-of-Cure (TOC) (Day 14) specimen. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).
Time frame: Day 14
Population: This analysis population includes all ITT subjects who were culture-positive at Day 1 in at least 1 ear (Microbiological Intent-to-Treat (MITT) analysis set).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EXE844 7 Days | Percentage of Subjects With Microbiological Success at Day 14 | 74.0 percentage of participants |
| EXE844 3 Days | Percentage of Subjects With Microbiological Success at Day 14 | 60.0 percentage of participants |
| Tubes Only | Percentage of Subjects With Microbiological Success at Day 14 | 50.0 percentage of participants |
Secondary
Time to Cessation of Otorrhea
Time (in days) to the cessation of otorrhea in the enrolled ear(s) was calculated as the number of days from the day of surgery to the absence of otorrhea (ie, no discharge) as reported by the parent/caregiver via the BID diary. Participants were considered a treatment failure if, at any time during the course of the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).
Time frame: Up to Day 14
Population: ITT analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EXE844 7 Days | Time to Cessation of Otorrhea | 2.5 days |
| EXE844 3 Days | Time to Cessation of Otorrhea | 1.5 days |
| Tubes Only | Time to Cessation of Otorrhea | 8.0 days |