Meniere Disease
Conditions
Keywords
Meniere's Disease, Vertigo, Endolymphatic Hydrops, Labyrinth Diseases, Ear Diseases, Otorhinolaryngologic Diseases
Brief summary
The purpose of this study is to evaluate the effectiveness of OTO-104 for the treatment of Meniere's disease.
Interventions
DRUGOTO-104
Single intratympanic injection of 12 mg dexamethasone
DRUGPlacebo
Single intratympanic injection of placebo
Sponsors
Otonomy, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Double-blind, Placebo-controlled, Multicenter
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of unilateral Meniere's disease by 1995 American Academy of Otolaryngology - Head and Neck Surgery (AAOHNS) criteria and reports active vertigo for the 2 months prior to the study lead-in period. * Subject has experienced active vertigo during the lead-in period. * Subject has documented asymmetric sensorineural hearing loss. * Subject agrees to maintain their current treatments for Meniere's disease while on-study.
Exclusion criteria
* Subject is pregnant or lactating. * Subject has a history of immunodeficiency disease. * Subject has a history of significant middle ear or inner ear surgery, or endolymphatic sac surgery in the affected ear. * Subject has a history of tympanostomy tubes with evidence of perforation or lack of closure. * Subject has a history of vestibular migraine. * Subject has used an investigational drug or device in the 3 months prior to screening. * Subject has previously been randomized to a clinical study of OTO-104.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-Day Average DVD at Week 12 (Month 3) | 3 months | The count of definitive vertigo days for Week 12 was determined during the 4-week period between Weeks 9 and 12. The 28-day average DVD was derived for each subject and visit by summing each subject's number of DVD counts within the 4-week interval, dividing by the number of completed diary days, and multiplying by 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Vertigo Experience on Daily Activities at Week 12 (Month 3) - The Number of Days Sick at Home or Bedridden | 3 Months | The count of days sick at home or bedridden for subsequent intervals was determined during the 4-week period between each visit. The count of days sick at home or bedridden was computed as the sum of the days in the Sick at home and Bedridden categories for each 4-week interval and was standardized to 28 days by multiplying by 28 days and dividing by the number of non-missing diary entries. |
| Otoscopic Examination - Presence of Perforation in the Treated Ear at Week 12 (Month 3) Final Visit | 3 months | Ear examinations were done at every visit. One of the important safety endpoints was an observation of a perforation in the ear drum did not heal properly after the injection. Reported here are the Week 12 (Month 3) final visit. |
| Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3) | Week 12 (Month 3) | The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 1000 Hz. |
| Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3) | Week 12 (Month 3) | The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 2000 Hz. |
| Audiometry - Shift in Air-Bone Gap at 4000 Hz From Baseline to Week 12 (Month 3) | Week 12 (Month 3) | The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 4000 Hz. |
Countries
Belgium, Germany, Italy, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
148 subjects were randomized and 148 subjects received study drug. The most common reason for screen failure was that there was not a sufficient number of definitive vertigo days in the 28-day lead-in period.
Pre-assignment details
In addition to meeting all screening visit inclusion criteria, potential subjects had to experience and record at least 4 and a maximum of 22 definitive vertigo day (DVD) during the 4-week lead-in period, where no intervention was administered. Also, the subject needed to complete at least 22 of 28 diary entries during this lead-in period. A DVD was defined as each day the subject recorded a vertigo episode lasting at least 20 minutes corresponding to a vertigo score of 2 or more.
Participants by arm
| Arm | Count |
|---|---|
| OTO-104 OTO-104: Single intratympanic injection of 12 mg dexamethasone | 73 |
| Placebo Placebo: Single intratympanic injection of placebo | 75 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | OTO-104 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 18 Participants | 40 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 57 Participants | 108 Participants |
| Age, Continuous | 57.0 years | 57.0 years | 57.0 years |
| Duration of Meniere's disease 11-15 years | 0 Participants | 4 Participants | 4 Participants |
| Duration of Meniere's disease >15 years | 3 Participants | 5 Participants | 8 Participants |
| Duration of Meniere's disease <5 years | 61 Participants | 53 Participants | 114 Participants |
| Duration of Meniere's disease 6-10 years | 9 Participants | 13 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 73 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 73 Participants | 71 Participants | 144 Participants |
| Region of Enrollment Belgium | 3 participants | 6 participants | 9 participants |
| Region of Enrollment Germany | 11 participants | 4 participants | 15 participants |
| Region of Enrollment Italy | 7 participants | 5 participants | 12 participants |
| Region of Enrollment Poland | 31 participants | 29 participants | 60 participants |
| Region of Enrollment Spain | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Turkey | 3 participants | 8 participants | 11 participants |
| Region of Enrollment United Kingdom | 7 participants | 9 participants | 16 participants |
| Region of Enrollment United States | 8 participants | 13 participants | 21 participants |
| Sex: Female, Male Female | 44 Participants | 44 Participants | 88 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 73 | 0 / 75 |
| other Total, other adverse events | 26 / 73 | 27 / 75 |
| serious Total, serious adverse events | 2 / 73 | 2 / 75 |
Outcome results
Primary
28-Day Average DVD at Week 12 (Month 3)
The count of definitive vertigo days for Week 12 was determined during the 4-week period between Weeks 9 and 12. The 28-day average DVD was derived for each subject and visit by summing each subject's number of DVD counts within the 4-week interval, dividing by the number of completed diary days, and multiplying by 28.
Time frame: 3 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| OTO-104 Intent to Treat | 28-Day Average DVD at Week 12 (Month 3) | 2.869 DVD |
| Placebo Intent to Treat | 28-Day Average DVD at Week 12 (Month 3) | 3.577 DVD |
p-value: 0.31295% CI: [-0.648, 0.207]Regression, Linear
Secondary
Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3)
The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 1000 Hz.
Time frame: Week 12 (Month 3)
Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OTO-104 Intent to Treat | Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3) | 5 Participants |
| Placebo Intent to Treat | Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3) | 7 Participants |
Secondary
Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3)
The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 2000 Hz.
Time frame: Week 12 (Month 3)
Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OTO-104 Intent to Treat | Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3) | 4 Participants |
| Placebo Intent to Treat | Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3) | 4 Participants |
Secondary
Audiometry - Shift in Air-Bone Gap at 4000 Hz From Baseline to Week 12 (Month 3)
The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (\<= 10 dB) to impairment at Month 3 (\>10 dB) when measured at 4000 Hz.
Time frame: Week 12 (Month 3)
Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OTO-104 Intent to Treat | Audiometry - Shift in Air-Bone Gap at 4000 Hz From Baseline to Week 12 (Month 3) | 2 Participants |
| Placebo Intent to Treat | Audiometry - Shift in Air-Bone Gap at 4000 Hz From Baseline to Week 12 (Month 3) | 9 Participants |
Secondary
Impact of Vertigo Experience on Daily Activities at Week 12 (Month 3) - The Number of Days Sick at Home or Bedridden
The count of days sick at home or bedridden for subsequent intervals was determined during the 4-week period between each visit. The count of days sick at home or bedridden was computed as the sum of the days in the Sick at home and Bedridden categories for each 4-week interval and was standardized to 28 days by multiplying by 28 days and dividing by the number of non-missing diary entries.
Time frame: 3 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OTO-104 Intent to Treat | Impact of Vertigo Experience on Daily Activities at Week 12 (Month 3) - The Number of Days Sick at Home or Bedridden | 0.998 days | Standard Deviation 2.1521 |
| Placebo Intent to Treat | Impact of Vertigo Experience on Daily Activities at Week 12 (Month 3) - The Number of Days Sick at Home or Bedridden | 1.643 days | Standard Deviation 2.5783 |
Secondary
Otoscopic Examination - Presence of Perforation in the Treated Ear at Week 12 (Month 3) Final Visit
Ear examinations were done at every visit. One of the important safety endpoints was an observation of a perforation in the ear drum did not heal properly after the injection. Reported here are the Week 12 (Month 3) final visit.
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OTO-104 Intent to Treat | Otoscopic Examination - Presence of Perforation in the Treated Ear at Week 12 (Month 3) Final Visit | 0 Participants |
| Placebo Intent to Treat | Otoscopic Examination - Presence of Perforation in the Treated Ear at Week 12 (Month 3) Final Visit | 0 Participants |