Trial Outcomes & Findings for OTO-313 in Subjects With Unilateral Subjective Tinnitus (NCT NCT04829214)

Last Updated: 2023-01-06

Results Overview

The TFI is a validated, 25-item questionnaire; index score from 0 to 100; higher scores indicate a greater problem with tinnitus. A responder is considered as any subject with at least a 13-point improvement from Baseline on the (TFI). This responder analysis required both Week 4 and Week 8 to have a 13-point improvement from Baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

153 participants

Primary outcome timeframe

Week 4 and Week 8 (both had to meet criterion for the subject to be considered a "responder")

Results posted on

2023-01-06

Participant Flow

Overall, 56 clinical centers were approved in Germany, Poland, United States, and United Kingdom to conduct this study. Thirty-six centers enrolled subjects. First subject was randomized 04 May 2021; Last subject was randomized 21 February 2022.

All subjects registered for this study signed an informed consent and entered a lead-in period. Following Lead-in, 153 subjects were randomized (=Full Analysis Set) and 151 subjects received study drug (=Safety Analysis Set). The most common reason for not being randomized was too low a score on the Tinnitus Functional Index (TFI)..

Participant milestones

Participant milestones
Measure	OTO-313 OTO-313: Single intratympanic 200 microliter injection of gacyclidine solution in medium chain triglycerides (0.16 mg/mL)	Placebo Placebo: Single intratympanic 200 microliter injection of medium chain triglycerides (OTO-313 vehicle)
Randomization STARTED	77	76
Randomization COMPLETED	77	76
Randomization NOT COMPLETED	0	0
Follow-up and Efficacy Analysis STARTED	77	76
Follow-up and Efficacy Analysis COMPLETED	70	72
Follow-up and Efficacy Analysis NOT COMPLETED	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	OTO-313 OTO-313: Single intratympanic 200 microliter injection of gacyclidine solution in medium chain triglycerides (0.16 mg/mL)	Placebo Placebo: Single intratympanic 200 microliter injection of medium chain triglycerides (OTO-313 vehicle)
Follow-up and Efficacy Analysis Withdrawal by Subject	5	3
Follow-up and Efficacy Analysis Lost to Follow-up	2	1

Baseline Characteristics

OTO-313 in Subjects With Unilateral Subjective Tinnitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OTO-313 n=77 Participants OTO-313: Single intratympanic injection	Placebo n=76 Participants Placebo: Single intratympanic injection	Total n=153 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 12.75 • n=5 Participants	50.8 years STANDARD_DEVIATION 15.22 • n=7 Participants	51.6 years STANDARD_DEVIATION 14.01 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	38 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants	68 Participants n=7 Participants	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 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	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	67 Participants n=5 Participants	68 Participants n=7 Participants	135 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	57 participants n=5 Participants	57 participants n=7 Participants	114 participants n=5 Participants
Region of Enrollment Poland	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Germany	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Duration of Tinnitus ≥2 to ≤6 months	33 Participants n=5 Participants	33 Participants n=7 Participants	66 Participants n=5 Participants
Duration of Tinnitus >6 to ≤12 months	44 Participants n=5 Participants	43 Participants n=7 Participants	87 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 4 and Week 8 (both had to meet criterion for the subject to be considered a "responder")

Outcome measures

Outcome measures
Measure	OTO-313 Full Analysis Set n=77 Participants The OTO-313 full analysis set includes all subjects randomized to OTO-313 and analyzed in this group utilizing the intent-to-treat principle.	Placebo Full Analysis Set n=76 Participants The placebo full analysis set includes all subjects randomized to placebo and analyzed in this group utilizing the intent-to-treat principle.
Percentage of Tinnitus Functional Index (TFI) Responders at Weeks 4 and at Week 8	20 Participants	27 Participants

SECONDARY outcome

Timeframe: The average is calculated for the Baseline and for each study week. Reported here is the change from Baseline to Week 8.

Numerical rating scale (NRS) from 0 (No Tinnitus) to 10 (Extremely Loud Tinnitus) collected every day. Post-baseline weekly NRS scores will be calculated as the average score of all recorded diary entries within each study week.

Outcome measures

Outcome measures
Measure	OTO-313 Full Analysis Set n=77 Participants The OTO-313 full analysis set includes all subjects randomized to OTO-313 and analyzed in this group utilizing the intent-to-treat principle.	Placebo Full Analysis Set n=76 Participants The placebo full analysis set includes all subjects randomized to placebo and analyzed in this group utilizing the intent-to-treat principle.
Change From Baseline in Daily Tinnitus Loudness at Week 8	-0.67 units on a scale Standard Deviation 1.767	-0.90 units on a scale Standard Deviation 1.557

SECONDARY outcome

Timeframe: The average is calculated for the Baseline and for each study week. Reported here is the change from Baseline to Week 8

Numerical rating scale from 0 (Not Annoying) to 10 (Extremely Annoying) collected every day. Post-baseline weekly NRS scores will be calculated as the average score of all recorded diary entries within each study week.

Outcome measures

Outcome measures
Measure	OTO-313 Full Analysis Set n=77 Participants The OTO-313 full analysis set includes all subjects randomized to OTO-313 and analyzed in this group utilizing the intent-to-treat principle.	Placebo Full Analysis Set n=76 Participants The placebo full analysis set includes all subjects randomized to placebo and analyzed in this group utilizing the intent-to-treat principle.
Change From Baseline in Daily Tinnitus Annoyance at Week 8	-0.73 units on a scale Standard Deviation 1.910	-1.11 units on a scale Standard Deviation 1.804

SECONDARY outcome

Timeframe: Week 8 reported here

Change in overall tinnitus status as perceived by the subject as assessed at the Week 8 visit. Subjects were asked, "Since the beginning of the clinical study, how would you rate your tinnitus?" and had the choice to answer from very much worse (-3) to very much improved (3). The mean change from baseline at Week 8 is reported here.

Outcome measures

Outcome measures
Measure	OTO-313 Full Analysis Set n=77 Participants The OTO-313 full analysis set includes all subjects randomized to OTO-313 and analyzed in this group utilizing the intent-to-treat principle.	Placebo Full Analysis Set n=76 Participants The placebo full analysis set includes all subjects randomized to placebo and analyzed in this group utilizing the intent-to-treat principle.
Patient Global Impression of Change at Week 8	0.32 score on a scale Standard Error 0.139	0.36 score on a scale Standard Error 0.138

OTHER_PRE_SPECIFIED outcome

Timeframe: After dosing (Baseline) up to end of study (16 Weeks)

Ear examinations were done at every visit. One of the important safety endpoints is an observation of a perforation in the ear drum that did not heal properly after the injection. Reported here are the Week 16 (final visit) results.

Outcome measures

Outcome measures
Measure	OTO-313 Full Analysis Set n=77 Participants The OTO-313 full analysis set includes all subjects randomized to OTO-313 and analyzed in this group utilizing the intent-to-treat principle.	Placebo Full Analysis Set n=74 Participants The placebo full analysis set includes all subjects randomized to placebo and analyzed in this group utilizing the intent-to-treat principle.
Otoscopic Examinations - Presence of Perforation in the Treated Ear at Week 16 (Final Visit)	0 Participants	0 Participants

Adverse Events

OTO-313 Safety Analysis Set

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo Safety Analysis Set

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OTO-313 Safety Analysis Set n=77 participants at risk Subjects randomized to OTO-313 and received a dose of OTO-313.	Placebo Safety Analysis Set n=76 participants at risk Subjects randomized to placebo and received placebo.
Vascular disorders Arteriosclerosis	1.3% 1/77 • Number of events 1 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	0.00% 0/76 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Cardiac disorders Myocardial ischaemia	1.3% 1/77 • Number of events 1 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	0.00% 0/76 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).

Other adverse events

Other adverse events
Measure	OTO-313 Safety Analysis Set n=77 participants at risk Subjects randomized to OTO-313 and received a dose of OTO-313.	Placebo Safety Analysis Set n=76 participants at risk Subjects randomized to placebo and received placebo.
Vascular disorders Hypertension	0.00% 0/77 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	2.6% 2/76 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Investigations Blood Potassium Increased	0.00% 0/77 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	2.6% 2/76 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Nervous system disorders Headache	1.3% 1/77 • Number of events 1 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	2.6% 2/76 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Ear and labyrinth disorders Tinnitus	10.4% 8/77 • Number of events 8 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	10.5% 8/76 • Number of events 8 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Ear and labyrinth disorders Vertigo	2.6% 2/77 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	1.3% 1/76 • Number of events 1 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Psychiatric disorders Insomnia	3.9% 3/77 • Number of events 3 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	1.3% 1/76 • Number of events 1 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Infections and infestations COVID-19	6.5% 5/77 • Number of events 5 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	9.2% 7/76 • Number of events 7 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Infections and infestations Urinary Tract Infection	2.6% 2/77 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	0.00% 0/76 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Infections and infestations Nasopharyngitis	2.6% 2/77 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	0.00% 0/76 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).
Infections and infestations Viral Sinusitis	0.00% 0/77 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).	2.6% 2/76 • Number of events 2 • Adverse events were recorded as observed or reported during or after dosing up to the final visit (Week 16).

Additional Information

Medical Information

Otonomy, Inc.

Phone: +1 844-686-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60