Otitis Media With Effusion
Conditions
Keywords
otitis media, otorrhea, middle ear effusion, tympanostomy tubes
Brief summary
The purpose of this study is to confirm the effectiveness, safety and tolerability of OTO-201 in the treatment of pediatric subjects with bilateral middle ear effusion who require tympanostomy tube placement.
Detailed description
This is a prospective, randomized, double-blind, sham-controlled, multicenter, Phase 3 study of OTO-201 administered intraoperatively in pediatric subjects with bilateral middle ear effusion requiring TT (tympanostomy tube) placement. One dose level (6 mg) of OTO-201 was evaluated relative to sham (empty syringe). Study subjects are required to have a clinical diagnosis of bilateral middle ear effusion requiring TT placement. On the day of surgery, prior to surgery, eligible subjects were examined via otoscope to confirm bilateral middle ear effusion. Subjects with bilateral middle ear effusion were randomized to either 6 mg OTO-201 or sham. Subjects without bilateral effusion on the day of surgery were not randomized and were considered screen failures. Approximately 264 subjects are planned to be randomized to OTO-201 or sham using a 2:1 allocation ratio. Randomization to OTO-201 or sham was stratified by age: 6 months to 2 years or \>2 years. Subjects are to visit the study site for safety assessments and otoscopic examination on Days 4, 8, 15, and 29. The assessment of otorrhea by the blinded assessor for the primary efficacy endpoint occurred on Days 4, 8, and 15.
Interventions
DRUGOTO-201
Single, intratympanic injection
DRUGSham
Simulated single, intratympanic injection
Sponsors
Otonomy, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
includes, but is not limited to: * Subject is a male or female aged 6 months to 17 years, inclusive * Subject has a clinical diagnosis of bilateral middle ear effusion requiring tympanostomy tube placement * Subject's caregiver is willing to comply with the protocol and attend all study visits
Exclusion criteria
includes, but is not limited to: * Subject has a history of prior ear or mastoid surgery, not including myringotomy or myringotomy with tympanostomy tube placement * Subject has a history of sensorineural hearing loss * Subject has a history of chronic or recurrent bacterial infections other than otitis media that likely will require treatment with antibiotics during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Treatment Failures. | Day 15 - 2 weeks after dosing | Cumulative proportion of treatment failures: The efficacy endpoint for both trials was the cumulative proportion of study treatment failures through Day 15, defined as the occurrence of any of the following events: otorrhea as determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason any time post-surgery, as well as patients who missed visits or were lost-to-follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Up to one month | Safety variables included the frequency of adverse events (AEs) and results from otoscopic examinations, tympanometry, audiometry measurements. |
| Microbiological Response | Day 15 - 2 weeks after dosing | Subjects whose samples tested positive for bacteria in either or both ears at baseline with documented eradication or presumed eradication post-baseline. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 19 centers, 18 in the United States and 1 in Canada
Pre-assignment details
Reporting group = all randomized participants (n=266). Safety analysis set = all subjects who receive study drug or sham and analyzed according to what they received. Full analysis set = all randomized subjects and analyzed according to randomized treatment regardless of the actual treatment received.
Participants by arm
| Arm | Count |
|---|---|
| OTO-201 OTO-201: Single, intratympanic injection:
One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery. | 178 |
| Sham Sham: Simulated single, intratympanic injection:
One sham injection into each ear during surgery. | 88 |
| Total | 266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | OTO-201 | Sham | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 178 Participants | 88 Participants | 266 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 2.279 years STANDARD_DEVIATION 1.901 | 2.863 years STANDARD_DEVIATION 2.5942 | 2.472 years STANDARD_DEVIATION 2.1677 |
| Sex: Female, Male Female | 82 Participants | 40 Participants | 122 Participants |
| Sex: Female, Male Male | 96 Participants | 48 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 178 | 40 / 87 |
| serious Total, serious adverse events | 0 / 178 | 0 / 87 |
Outcome results
Primary
Percentage of Participants Who Were Treatment Failures.
Cumulative proportion of treatment failures: The efficacy endpoint for both trials was the cumulative proportion of study treatment failures through Day 15, defined as the occurrence of any of the following events: otorrhea as determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason any time post-surgery, as well as patients who missed visits or were lost-to-follow-up.
Time frame: Day 15 - 2 weeks after dosing
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTO-201 | Percentage of Participants Who Were Treatment Failures. | 21.3 percentage of treatment failures |
| Sham | Percentage of Participants Who Were Treatment Failures. | 45.5 percentage of treatment failures |
Secondary
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry
Safety variables included the frequency of adverse events (AEs) and results from otoscopic examinations, tympanometry, audiometry measurements.
Time frame: Up to one month
Population: Safety Analysis Set (number of ears is equivalent to number of participants)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Otoscopic abnormal exams @ day 29-left ear | 1.7 percentage of ears |
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Otoscopic abnormal exams @ day 29-right ear | 1.7 percentage of ears |
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Audiometry Patent tubes @ day 29 left ear | 96.0 percentage of ears |
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Audiometry Patent tubes @ day 29 right ear | 96.0 percentage of ears |
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Tympanometry Category of B (large) day 29 left ear | 87.9 percentage of ears |
| OTO-201 | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Tympanometry Category of B (large)day 29 right ear | 88.2 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Tympanometry Category of B (large) day 29 left ear | 87.1 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Otoscopic abnormal exams @ day 29-left ear | 2.4 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Audiometry Patent tubes @ day 29 right ear | 96.5 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Otoscopic abnormal exams @ day 29-right ear | 3.5 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Tympanometry Category of B (large)day 29 right ear | 84.5 percentage of ears |
| Sham | Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry | Audiometry Patent tubes @ day 29 left ear | 100 percentage of ears |
Secondary
Microbiological Response
Subjects whose samples tested positive for bacteria in either or both ears at baseline with documented eradication or presumed eradication post-baseline.
Time frame: Day 15 - 2 weeks after dosing
Population: Microbiologically Evaluable Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTO-201 | Microbiological Response | 83 percentage of Microbiological response |
| Sham | Microbiological Response | 48 percentage of Microbiological response |