Trial Outcomes & Findings for Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere's Disease (NCT NCT03664674)
NCT ID: NCT03664674
Last Updated: 2022-12-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
148 participants
Primary outcome timeframe
3 months
Results posted on
2022-12-07
Participant Flow
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.
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.
Participant milestones
| Measure |
OTO-104
OTO-104: Single intratympanic injection of 12 mg dexamethasone
|
Placebo
Placebo: Single intratympanic injection of placebo
|
|---|---|---|
|
Overall Study
STARTED
|
73
|
75
|
|
Overall Study
COMPLETED
|
70
|
73
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
OTO-104
OTO-104: Single intratympanic injection of 12 mg dexamethasone
|
Placebo
Placebo: Single intratympanic injection of placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere's Disease
Baseline characteristics by cohort
| Measure |
OTO-104
n=73 Participants
OTO-104: Single intratympanic injection of 12 mg dexamethasone
|
Placebo
n=75 Participants
Placebo: Single intratympanic injection of placebo
|
Total
n=148 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
51 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Age, Continuous
|
57.0 years
n=5 Participants
|
57.0 years
n=7 Participants
|
57.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
71 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
73 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
3 participants
n=5 Participants
|
8 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
13 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
31 participants
n=5 Participants
|
29 participants
n=7 Participants
|
60 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
7 participants
n=5 Participants
|
9 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
11 participants
n=5 Participants
|
4 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Duration of Meniere's disease
<5 years
|
61 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
|
Duration of Meniere's disease
6-10 years
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Duration of Meniere's disease
11-15 years
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Duration of Meniere's disease
>15 years
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsThe 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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=73 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=75 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
28-Day Average DVD at Week 12 (Month 3)
|
2.869 DVD
Interval 2.109 to 3.903
|
3.577 DVD
Interval 2.641 to 4.844
|
SECONDARY outcome
Timeframe: 3 MonthsThe 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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=73 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=75 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
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
|
1.643 days
Standard Deviation 2.5783
|
SECONDARY outcome
Timeframe: 3 monthsEar 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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=73 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=75 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at Week 12 (Month 3) Final Visit
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 12 (Month 3)Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=55 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=58 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3)
|
5 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Week 12 (Month 3)Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=62 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=64 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3)
|
4 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Week 12 (Month 3)Population: Subjects that had no impairment at the Baseline visit (air-bone gap \<= 10 dB)
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.
Outcome measures
| Measure |
OTO-104 Intent to Treat
n=50 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
Placebo Intent to Treat
n=53 Participants
Includes all randomized subjects who received study drug. Subjects were included in the treatment group to which they were randomized regardless of the actual study drug received.
|
|---|---|---|
|
Audiometry - Shift in Air-Bone Gap at 4000 Hz From Baseline to Week 12 (Month 3)
|
2 Participants
|
9 Participants
|
Adverse Events
OTO-104
Serious events: 2 serious events
Other events: 26 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
OTO-104
n=73 participants at risk
OTO-104: Single intratympanic injection of 12 mg dexamethasone
|
Placebo
n=75 participants at risk
Placebo: Single intratympanic injection of placebo
|
|---|---|---|
|
Infections and infestations
COVID-19
|
1.4%
1/73 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
0.00%
0/75 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Reproductive system and breast disorders
Uterine Haemorrhage
|
1.4%
1/73 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
0.00%
0/75 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Meniere's disease
|
0.00%
0/73 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
1.3%
1/75 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/73 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
1.3%
1/75 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
Other adverse events
| Measure |
OTO-104
n=73 participants at risk
OTO-104: Single intratympanic injection of 12 mg dexamethasone
|
Placebo
n=75 participants at risk
Placebo: Single intratympanic injection of placebo
|
|---|---|---|
|
Ear and labyrinth disorders
Meniere's disease
|
8.2%
6/73 • Number of events 6 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
8.0%
6/75 • Number of events 6 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Tinnitus
|
6.8%
5/73 • Number of events 5 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
0.00%
0/75 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Vertigo
|
5.5%
4/73 • Number of events 4 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
9.3%
7/75 • Number of events 7 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Ear Discomfort
|
2.7%
2/73 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
2.7%
2/75 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Ear Pain
|
1.4%
1/73 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
5.3%
4/75 • Number of events 4 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Ear and labyrinth disorders
Tympanic Membrane Disorders
|
0.00%
0/73 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
2.7%
2/75 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Infections and infestations
Upper Respiratory Infection
|
2.7%
2/73 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
2.7%
2/75 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Infections and infestations
Nasopharyngitis
|
1.4%
1/73 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
2.7%
2/75 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Injury, poisoning and procedural complications
Limb Injury
|
2.7%
2/73 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
0.00%
0/75 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Injury, poisoning and procedural complications
Fall
|
1.4%
1/73 • Number of events 1 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
2.7%
2/75 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
|
Nervous system disorders
Headache
|
2.7%
2/73 • Number of events 2 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
0.00%
0/75 • Reported or observed during or after dosing with the study drug up until end of study (Week 12/Month 3).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60