Trial Outcomes & Findings for OTO-313 in Subjects With Subjective Tinnitus (NCT NCT03918109)
NCT ID: NCT03918109
Last Updated: 2022-12-23
Results Overview
Mean Change from Baseline to End of Study (baseline to Day 29 \[4 weeks after dosing\](Part A) or baseline to Day 57 \[8 weeks after dosing\] (Part B)). in Pure Tone Average Hearing Thresholds; a negative change indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Up to end of study (Part A - Day 29 [4 weeks after dosing]), (Part B - Day 57 [8 weeks after dosing])
Results posted on
2022-12-23
Participant Flow
For Part A, a total of 8 subjects registered for this study at a single site and signed an informed consent. Subject needed to have subjective unilateral or bilateral tinnitus (ringing or noise in the ear when there was no external cause) and be consistently aware of their tinnitus throughout much of the waking day.
Part A and Part B were conducted as 2 separate studies under a single protocol.
Participant milestones
| Measure |
Part A OTO-313
Subjects received an 0.11 mg OTO-313 via an injection through the eardrum (IT injection) of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
Subjects received an injection through the eardrum of 0.2 mL medium chain triglycerides.
|
Part B OTO-313
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
2
|
17
|
18
|
|
Overall Study
COMPLETED
|
6
|
2
|
15
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
2
|
2
|
Reasons for withdrawal
| Measure |
Part A OTO-313
Subjects received an 0.11 mg OTO-313 via an injection through the eardrum (IT injection) of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
Subjects received an injection through the eardrum of 0.2 mL medium chain triglycerides.
|
Part B OTO-313
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
Baseline Characteristics
OTO-313 in Subjects With Subjective Tinnitus
Baseline characteristics by cohort
| Measure |
Part A OTO-313
n=6 Participants
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=15 Participants
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=16 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Total
n=39 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Age, Continuous
|
64.0 years
n=5 Participants
|
57.0 years
n=7 Participants
|
58.0 years
n=5 Participants
|
55.0 years
n=4 Participants
|
57.5 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
15 participants
n=5 Participants
|
16 participants
n=4 Participants
|
39 participants
n=21 Participants
|
|
Months Since Initial Onset of Tinnitus
|
95.8 Months
STANDARD_DEVIATION 87.09 • n=5 Participants
|
49.0 Months
STANDARD_DEVIATION 16.42 • n=7 Participants
|
4.5 Months
STANDARD_DEVIATION 1.96 • n=5 Participants
|
4.20 Months
STANDARD_DEVIATION 1.62 • n=4 Participants
|
38.38 Months
STANDARD_DEVIATION 37.84 • n=21 Participants
|
PRIMARY outcome
Timeframe: Up to end of study (Part A - Day 29 [4 weeks after dosing]), (Part B - Day 57 [8 weeks after dosing])Mean Change from Baseline to End of Study (baseline to Day 29 \[4 weeks after dosing\](Part A) or baseline to Day 57 \[8 weeks after dosing\] (Part B)). in Pure Tone Average Hearing Thresholds; a negative change indicates improvement.
Outcome measures
| Measure |
Part A OTO-313
n=6 Participants
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=14 Participants
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=15 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Audiometry - Pure Tone Average Done Over 1000, 2000 and 4000 Hertz (HZ)
|
-0.3 decibels
Standard Deviation 2.66
|
0.71 decibels
Standard Deviation 2.5
|
-0.8 decibels
Standard Deviation 6.44
|
0.3 decibels
Standard Deviation 6.95
|
PRIMARY outcome
Timeframe: Up to end of study (Part A - Day 29 [4 weeks after the injection], Part B - Day 57 [8 weeks after the injection])Ear examinations were done at every visit. One of the important safety endpoints was an observation of a perforation in the ear drum that did not heal properly after the injection.
Outcome measures
| Measure |
Part A OTO-313
n=6 Participants
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=14 Participants
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=15 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at the End of Study Visit (Day 29 [4 Weeks After Dosing] (Part A) or Day 57 [8 Weeks After Dosing] (Part B)).
Perforation present: >25% and ≤50% tympanic membrane
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at the End of Study Visit (Day 29 [4 Weeks After Dosing] (Part A) or Day 57 [8 Weeks After Dosing] (Part B)).
Perforation present: >50% tympanic membrane
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at the End of Study Visit (Day 29 [4 Weeks After Dosing] (Part A) or Day 57 [8 Weeks After Dosing] (Part B)).
Perforation not present
|
6 Participants
|
2 Participants
|
14 Participants
|
15 Participants
|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at the End of Study Visit (Day 29 [4 Weeks After Dosing] (Part A) or Day 57 [8 Weeks After Dosing] (Part B)).
Perforation present: pinhole size
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Otoscopic Examination - Presence of Perforation in the Treated Ear at the End of Study Visit (Day 29 [4 Weeks After Dosing] (Part A) or Day 57 [8 Weeks After Dosing] (Part B)).
Perforation present: ≤25% tympanic membrane
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to the End of Study Visit (Part A - Day 29 [4 weeks after the injection]), (Part B - Day 57 [8 weeks after injection])Validated, 25-item questionnaire; index score from 0 to 100; a negative change indicates improvement. The 25 items of the TFI represent 8 subscales covering multiple domains of tinnitus severity: 1) Intrusive, 2) Sense of Control, 3) Cognitive, 4) Sleep, 5) Auditory, 6) Relaxation, 7) Quality of Life, and 8) Emotional. Subjects answer each TFI question by rating their experience over the past week. Each subscale has 3 questions with a response ranging from 0 (best response) to 10 (worst response) in regard to the impact of tinnitus in these different aspects of the subject's life. The highest raw score would be 250 and the lowest would be 0. The raw score is then divided by the total number of valid answers and that in turn is multiplied by 10 to give an overall score range from 0-100, with 0 representing no impact of tinnitus on their daily life and 100 representing complete impact of tinnitus on their daily life.
Outcome measures
| Measure |
Part A OTO-313
n=6 Participants
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=14 Participants
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=15 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Change From Baseline in Tinnitus Functional Index (TFI)
|
-4.2 score on a scale
Standard Deviation 10.68
|
4.0 score on a scale
Standard Deviation 0.00
|
-12.9 score on a scale
Standard Deviation 25.21
|
-4.3 score on a scale
Standard Deviation 18.18
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Measured at the end of study visit (Part A - Day 29 [4 weeks after injection]), (Part B - Day 57 [8 weeks after injection]).Change in overall tinnitus status as perceived by the subject; this was a subject-reported outcome that evaluated the change in overall "global" tinnitus status as perceived by the subject. The subject was asked: "Since the beginning of the clinical study, how would you rate your tinnitus?". The beginning of the clinical study in this context was the time prior to investigational product administration. The 7 response categories (and point scores) for the PGIC are: * Very much improved = 3 * Much improved = 2 * Minimally improved = 1 * Unchanged = 0 * Minimally worse = -1 * Much worse = -2 * Very much worse = -3
Outcome measures
| Measure |
Part A OTO-313
n=6 Participants
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=15 Participants
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=16 Participants
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Patient Global Impression of Change (PGIC)
Minimally improved
|
1 Participants
|
0 Participants
|
2 Participants
|
3 Participants
|
|
Patient Global Impression of Change (PGIC)
Very much improved
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Patient Global Impression of Change (PGIC)
Much improved
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Patient Global Impression of Change (PGIC)
Unchanged
|
3 Participants
|
2 Participants
|
5 Participants
|
10 Participants
|
|
Patient Global Impression of Change (PGIC)
Minimally worse
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Patient Global Impression of Change (PGIC)
Much worse
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Patient Global Impression of Change (PGIC)
Very much worse
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Part A OTO-313
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part A Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part B OTO-313
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Part B Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A OTO-313
n=6 participants at risk
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 participants at risk
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=17 participants at risk
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=18 participants at risk
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
Cardiac disorders
Stress Cardiomyopathy
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.9%
1/17 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/18 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
Other adverse events
| Measure |
Part A OTO-313
n=6 participants at risk
Subjects received 0.11 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part A Placebo
n=2 participants at risk
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B OTO-313
n=17 participants at risk
Subjects received 0.32 mg OTO-313 via an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
Part B Placebo
n=18 participants at risk
Subjects received an injection through the eardrum of a 0.2 mL medium chain triglycerides solution.
|
|---|---|---|---|---|
|
General disorders
Injection Site Discomfort
|
16.7%
1/6 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/17 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/18 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
General disorders
Injection Site Pain
|
16.7%
1/6 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/17 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/18 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
General disorders
Injection Site Pruritis
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
50.0%
1/2 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/17 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/18 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.9%
1/17 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
27.8%
5/18 • Number of events 5 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
Ear and labyrinth disorders
Ear Pain
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
11.8%
2/17 • Number of events 2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.6%
1/18 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
Ear and labyrinth disorders
Ear Discomfort
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.9%
1/17 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.6%
1/18 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/6 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
0.00%
0/2 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.9%
1/17 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
5.6%
1/18 • Number of events 1 • Reported or observed during or after dosing with the study drug up until the end of study (Part A - Day 29; Part B - Day 57)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60